Research Paul Cos

Abstract

Mycobacterium abscessus (Mab) is a nontuberculous mycobacterium (NTM) that causes opportunistic infections in patients with chronic lung diseases, like cystic fibrosis and chronic obstructive pulmonary disease and its incidence in disease is increasing. Infections with Mab are notoriously difficult to treat as it demonstrates a high resistance to antibiotics and the correlation between the in vitro susceptibility of Mab isolates and the clinical outcome is limited. For Mab lung diseases, the role of antibiotic tolerant persisters in disease and treatment has not been established. However, given the chronic nature of the disease, as well as the long duration of treatment and the frequent occurrence of relapses, we hypothesize that antibiotic tolerant persister formation is of great importance. Combining the multidisciplinary expertise of LMPH (UA) and the BREATHE/Microbiology lab (UZ/KUL) this project will provide fundamental knowledge about Mab antibiotic persistence such as i) levels of persister formation in different Mab clinical isolates under clinically relevant conditions for various antibiotic classes; ii) the mechanism behind antibiotic induced persister formation and iii) its importance in disease progression and treatment outcome. We strongly believe a thorough understanding of the mechanisms involved in persister formation will aid in the identification of potential new drug targets that can act on persistent Mab ultimately leading to improved treatment options.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Mycobacterium abscessus (Mab) is an increasingly emerging human pathogen responsible for a wide spectrum of diseases, including chronic pulmonary and skin infections. The treatment of Mab infections is a great challenge as it demonstrates a high resistance to antibiotics and the correlation between the in vitro susceptibility of Mab isolates and the clinical outcome is limited. For Mab lung diseases, the role of persisters in disease and treatment has not been established. However, given the chronic nature of the disease, as well as the long duration of treatment and the frequent occurrence of relapses, we hypothesize that persister formation could be of importance here. This project aims to increase fundamental knowledge about Mab persistence, such as frequency of persister formation for various antibiotic classes in different Mab isolates under standard and clinically relevant culture conditions and the molecular mechanisms involved in persister formation. Since Mab can replicate in macrophages, Mab persister levels in an intracellular environment will also be determined. We strongly believe a thorough understanding of the mechanisms involved in persister formation will aid in the identification of potential new drug targets that can act on persistent Mab ultimately leading to improved treatment options.

Researcher(s)

• Promoter: Cos Paul
• Fellow: Geerts Lisa

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Streptococcus pneumoniae (SP) is a leading cause of community-acquired pneumonia, with a concerning rise in drug-resistant strains. Central to its virulence is the high-temperature requirement A protease (HtrA), which plays a dual role as a chaperone and protease. HtrA is pivotal in SP's pathological processes, offering an innovative target for antibacterial strategies. Yet, the exact role of HtrA during infection remains elusive, posing challenges for drug development. This project aims to elucidate SP-HtrA's protease function during the infection process. We plan to develop activity-based probes (ABPs) for detecting and localizing active SP-HtrA proteases, alongside cyclic peptides as specific, irreversible inhibitors. These tools and inhibitors will contain a specific peptide scaffold, tailored to SP-HtrA's active site through advanced techniques, including positional scanning combinatorial libraries and phage display, ensuring specificity and avoiding interference with human HtrAs. We will demonstrate the power of these ABPs and inhibitors in both in vitro and in vivo infection models by offering proteomic insights into the activity status of SP-HtrA within an infection context. Overall, this project will provide a novel strategy to examine SP-HtrA protease activity during infection, which goes beyond the capabilities of conventional expression profiling technologies.

Researcher(s)

• Promoter: Prothiwa Michaela
• Co-promoter: Cos Paul
• Fellow: Verma Vani

Research team(s)

• Medicinal Chemistry (UAMC)

Project type(s)

• Research Project

Abstract

Despite the concept that infectious diseases are usually caused by a single pathogen, in reality, we are constantly challenged by multiple pathogens and growing evidence indicates that co-infections are a much more common event than clinically perceived. The respiratory tract is the first point of contact with airborne pathogens and the most common site for infections. Hence, human respiratory infections contribute to substantial morbidity and economic losses worldwide, resulting in approximately 2.5 million deaths each year. Recent findings have shed light on a crucial factor in the severity of respiratory infections: the role of co-infections. Considering the public health importance of respiratory infections and the scarcity of research on the impact of co-infections in the balance of immune defences, this project proposes to study the in vitro and in vivo effects of diverse parasitic, viral, and bacterial co-infections on different types of immune cellsin the lungs, and comprehensively characterize tissue local microenvironment and host-pathogen interactions. Additionally, we will investigate the immunomodulatory effects of protozoan infections on vaccines and chemotherapy treatments and their impact on the protection against targeted pathogens. Objectives include: elucidate the molecular mechanisms underlying immunological responses in the lungs and the susceptibility to co-infections; investigate altered immune responses of vaccines and the changes in the response to co-infection after chemotherapy of the primary infection. In the end, this study will allow deeper understanding of respiratory co infections that could pave the way for the development of improved diagnostic and prognostic techniques, as well as the potential for proposing supportive treatments and vaccines. Notwithstanding, the development of this project will open up new avenues for future co infection research and propel the fellow towards establishment as a successful independent researcher.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Cos Paul
• Co-promoter: Delputte Peter
• Fellow: Araujo Sergio

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Nosocomial infections are a major hurdle on intensive care units all over the world. Approximately 10% of the patients who stay two or more days in this unit, suffer from such infections, from which ventilator-associated pneumonia (VAP) is the most common. One of the most threatening bacteria that can cause this biofilm-related infection on the endotracheal tubes is Pseudomonas aeruginosa. The diagnosis is difficult and empirical antibiotic treatment is currently the only initial option during the first acute stage of the disease. This project aims to develop an anti-infective medical device that can be used in a preventive context.

Researcher(s)

• Promoter: Cos Paul
• Fellow: Wouters Milan

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This is a fundamental research project financed by the Research Foundation - Flanders (FWO). The aim of this research community is to better understand the formation and the structure of bacterial and fungal biofilms in humans. This could lead to a more efficient treatment of biofilm-related infections.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Non-tuberculous mycobacteria, such as Mycobacterium avium complex (MAC) and Mycobacterium abscessus, cause lung diseases resembling TB, mainly in immune-compromised patients or patients suffering from other lung diseases (e.g. cystic fibrosis). The incidence and prevalence of lung diseases caused by NTM are increasing worldwide. Importantly, in the US and Japan, as well as in other areas of the world where TB has declined, NTM disease is already at least three times more prevalent than TB. Treatment of NTM diseases relies on antibiotic combinations, however the drugs active against NTM are rather few and mainly different than those active against TB. These NTM treatments for the most common species (MAC and M. abscessus) are much less active than the current anti-TB regimen is for TB treatment. It is often necessary to administer antibiotic combinations for at least 12-24 months. The long and complex drug regimen that is currently recommended as a treatment against NTM-caused diseases carries the risk of inducing resistance in NTM. Several studies have already shown the existence and emergence of multidrug resistant NTM. The overall objective of RESPIRI-NTM is to find new drug candidates as potential components of a new, more efficient combination drug regimen against NTM that is less prone to resistance and allows shortening of treatment duration for NTM and multidrug-resistant NTM. Such a drug combination will synergistically target the energy metabolism of NTM or complementary targets. To achieve this, we will advance recently discovered inhibitors of the mycobacterial respiratory pathway. In addition, we will perform a novel, phenotypic screen in order to identify novel targets in NTM. Finally, we will also target host-factors that are essential for the intracellular survival of NTM. Together, we present a comprehensive plan to find novel strategies to combat non-tuberculous mycobacteria, shorten treatment time and reduce chances of drug resistance.

Researcher(s)

• Promoter: Augustyns Koen
• Co-promoter: Cos Paul
• Co-promoter: Maes Bert

Research team(s)

• Medicinal Chemistry (UAMC)

Project website

Project type(s)

• Research Project

Abstract

Despite recent progress in biomedical research, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is still the world's leading infectious disease killer worldwide. Treatment options are limited, and expensive, recommended medicines are not always available in many countries, and patients experience many adverse effects from the drugs. Thus, there is an acute need for the development of a novel combination regimen with an indication for effective, shorter, and safer treatment of all forms of TB. The overall objective of RESPIRI-TB is to find new drug candidates as potential components of a new, more efficient combination drug regimen against TB that is less prone to resistance and allows shortening of treatment duration for TB, and multidrug-resistant TB. Such a drug combination will synergistically target the energy metabolism of Mtb or complementary targets. To achieve this, we will advance recently discovered inhibitors of the Mtb respiratory pathway. In addition, we will target the Mtb specific molecular mechanism that reduces reactive oxygen species in the cell.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Cappoen Davie
• Co-promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The research aims at improving an existing EU project application on the development of in vitro and in vivo models to quantify nucleic acids internationalization in live bacterial cells, and thereby preparing it for resubmission in a next round. This research will have a major contribution to the discovery of novel antibacterials. The budget will be used primarily for the compilation and interpretation of preliminary data from new experiments, with a focus on the development of bioluminescent bacterial strains for in vivo research.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Human respiratory infections lead to a spectrum of respiratory symptoms and variable disease severity, contributing to substantial morbidity, mortality and economic losses worldwide. Respiratory pathogens can spread easily in the population and are specifically prone to cause large scale outbreaks, epidemics and even pandemics. While such pandemics have devastating impact on human health and cause major socio-economic disruptions, the annual burden of respiratory infections such as Respiratory Syncytial Virus (RSV), Mycobacterium tuberculosis and Streptococcus pneumoniae is also substantial. Respiratory infections are worldwide the number one cause of death in children below five years of age, with ~650.000 annual deaths. The disease burden however goes beyond this staggering number, with an overall effect on morbidity and mortality in the general population worldwide (~2.5 million deaths annually). Of particular interest, it has become very clear that severe disease upon respiratory infections not only depends on one particular pathogen, but also depends on other previous or simultaneous co-infections. The importance and impact of co-infection are however not yet fully clear. Therefore, there is an urgent need to enhance our understanding of host-pathogen interactions at the lung (immune) interface and to develop clinically relevant animal models. Laboratory animal studies are a cornerstone of basic research and the development of novel prophylactic, diagnostic and therapeutic modalities. However, the development of suitable infection models can be notoriously daunting, often resulting in very narrow assay windows due to rapid pathogen clearance or early mortality of the host. The research teams involved in this challenge have longstanding expertise with infection models, both in vitro and in rodents. Three PIs focus their research on parasitic (prof. Caljon), viral (Prof. Delputte) and bacterial infections (Prof. Cos) to gain understanding of protective innate and adaptive immune responses, and of (immune) pathology. A recent study in which LMPH was involved demonstrated that some lung bacteria have an immune modulatory role in chronic respiratory diseases (Rigauts et al., Eur. Resp. J., 2022). Very recent parasitological observations show that African trypanosomes rapidly and permanently colonize the lung tissue with substantial changes in the immunological repertoire (reductions in B cells and eosinophils) but without overt respiratory dysfunction or pathology. Surprisingly, RSV challenge revealed a higher susceptibility with an enhanced and sustained viral replication, hinting at complex in vivo interactions that cannot be modelled in vitro (Mabille et al., Nat. Commun., pending acceptance). Exploiting the expertise with parasitic, viral and bacterial infections at LMPH, the established high-end platforms for evaluating lung function and immunological correlates and initiatives of biobanking, this challenge aims to functionally and immunologically characterize pulmonary infections and co-infections of parasitic, viral and bacterial origin. This will provide invaluable information on virulence and pathogenicity of selected strains from in-house collections, establishment of in vivo read-out assays and immunological correlates of induced pathology. Besides progressing basic scientific insights in host-pathogen interactions, the applications are numerous including the development and evaluation of diagnostics and medicinal compounds.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Cos Paul
• Co-promoter: Delputte Peter
• Fellow: Araujo Sergio

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Bacterial infections play an important role in many lung diseases, including infective exacerbations of chronic obstructive lung disease (COPD) or community-acquired pneumonia (CAP), one of the most frequently diagnosed diseases worldwide. In order to infect the lung, bacterial pathogens produce numerous proteases with essential functions in cell viability, physiology and virulence. For example, Elastase B of Pseudomonas aeruginosa causes extensive lung damage during pneumonia. These proteases are promising candidates as both antimicrobial drug target and biomarker for lung infection. However, the precise mechanisms in which they contribute to virulence is often unclear, hampering drug and biomarker discovery. The research topic described herein uses the power of chemical probes to understand the virulent roles of bacterial proteases, for which we currently lack the tools to determine. The selected candidate will develop highly sensitive and selective chemical probes that will report on bacterial proteases activity in infection models and patient samples. This will allow to (1) uncover yet unknown virulence functions of bacterial proteases in lung diseases, such as biofilm formation and persistence and (2) evaluate bacterial proteases as potential biomarkers for bacterial lung infections. The two major groups of chemical tools to profile protease activity are activity-based probes (ABPs) and substrate probes. ABPs are small molecules that bind covalently to the active site of target enzymes. They usually contain a recognition sequence, a detection tag and an electrophilic or photoreactive group to bind into the active site. Substrate probes typically comprise of recognition sequences flanked by reagents that generate a fluorescent readout after cleavage. The candidate will synthesize such tools based on known inhibitors or substrates of bacterial proteases produced by pathogens involved in lung diseases, such as Haemophilus influenzae or Streptococcus pneumoniae. Many lung pathogens exert a particularly virulent behaviour by persisting inside epithelial cells, allowing them to evade the human immune response and antibiotic treatment. However, the role of bacterial proteases during persistence is often unknown. Thus, the candidate will apply the new probes, after biochemical validation, in in vitro and in vivo infection models to monitor the enzyme activity during persistence (collaboration with Prof. Paul Cos). Moreover, due to their high selectivity for the respective bacterial proteases, the novel tools will be perfectly suited as activity-based diagnostics. Although diagnosis is critical in acute respiratory illness, diagnostic tests that rapidly clarify the causative pathogen are often lacking and urgently needed. Therefore, the candidate will apply the probes in samples of hospitalized patients with lung infections and evaluate them as potential activity-based diagnostic tools (collaboration with Prof. Thérèse Lapperre).

Researcher(s)

• Promoter: Augustyns Koen
• Co-promoter: Cos Paul
• Co-promoter: Lapperre Therese
• Fellow: Verma Vani

Research team(s)

• Medicinal Chemistry (UAMC)

Project type(s)

• Research Project

Abstract

This application relates to the purchase of new basic research infrastucture, a device for versatile Single Cell Sorting and Dispensing using Microfluidics. The equipment can be used for a variety of applications, including cell line development, monoclonal antibody development, iPSC cloning, single cell omics, rare cell isolation, microbiology, virology, immunology and microbial technology. The equipment works at low pressure and allows easy setup and easy switching between a variety of applications, both with or without infectious agents.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: Cos Paul
• Co-promoter: Lebeer Sarah
• Co-promoter: Ogunjimi Benson
• Co-promoter: Vorsters Alex

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This research project focuses on dry eye disease (DED) which is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. DED can be divided into tear-deficient and evaporative types. Evaporative dry eye can be divided into Meibomian gland disease (MGD) and exposure-related dry eye. MGD is the most common cause of evaporative DED and it is defined as "a chronic, diffuse abnormality of the Meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion". Research on the MGD is a priority. An appropriate animal model is an essential tool for translational research with the final goal to find better treatments for DED. This project is a continuation of the MSCA-ITN IT-DED3 project. One of the biggest challenges is to evaluate the cytokine profile in a low amount of rat tear fluids. Preliminary results with a customized multiplex (3plex) Enzyme Linked Immunosorbent Assay (ELISA) are promising and the assay will be further optimized and validated. The evaporative dry eye animal model will be further optimized based on the previous results. To minimize the number of animal experiments, a cell culture model in which DED is induced through the use of hyperosmolar stress is also under development and focuses on monocytes and corneal and conjunctival epithelial cells. This will allow us to test the most promising anti-inflammatory compounds for their antioxidant activity in a cellular model.

Researcher(s)

• Promoter: Cos Paul
• Fellow: Compagnone Agnese

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Streptococcus pneumoniae is an important human pathogen, as it is one of the most common causes of community-acquired pneumonia and otitis media. Several issues arise when battling these infections. First, replacement of vaccine-serotypes by new ones has been observed. Second, antibiotic resistance is an emerging problem. Also, antibiotic persistence is considered an important, yet underexposed phenomenon. Persister cells are a subpopulation of cells that are tolerant to lethal concentrations of antibiotics and are involved in a variety of chronic and recurrent infections. However, little to nothing is known about persister formation in S. pneumoniae. This project aims to fill this gap in knowledge. As in vitro autolysis hampers the prolonged monitoring of cultures, a variety of strategies – including the generation of mutant strains – will be applied to overcome this issue. Using heritability assays and gene sequencing to exclude arising of antimicrobial resistance, the presence of persisters will be confirmed. Furthermore, an in vivo model for persister studies will be optimized to confirm the clinical relevance of in vitro results. Lastly, the propensity to form persisters, the antimicrobial susceptibility profile, the strain origin and the in vivo virulence of a set of 50 clinical isolates will be evaluated. Collectively, this project will significantly progress our understanding of importance of persisters in the pathology of S. pneumoniae infections.

Researcher(s)

• Promoter: Cos Paul
• Fellow: Geerts Nele

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Biofilm formation during lung infection is related to persistent infection. This is a characteristic of chronic diseases such as Cystic Fibrosis (CF). Moreover, biofilm formation in endotracheal tubes (ETT) is related to the onset of Ventilator-Associated Pneumonia (VAP). Failure in treatment is associated with high morbidity and mortality. In addition to increased resistance, antibiotic therapy failure can also result from regrowth of a subset of cells in bacterial populations that are called persisters. When challenged with a lethal dose of antibiotics, this small fraction of transiently antibiotic tolerant cells survives to give origin to a new population and they are then related to the chronic nature of pneumonia. Therefore, new ideas to prevent and treat biofilm-related lung infections are required. New antibacterial targets and incorporation of antibacterial compounds in 3D printed catheters are being investigated. A chronic P. aeruginosa lung infection model, based on intratracheal infection of bacteria encapsulated in seaweed alginate beads, was optimized to characterize persistence in collaboration with KULeuven. This animal model mimics cystic fibrosis (CF) and several low and high persister laboratory strains are currently being studied in vivo to validate the infection dose and the treatment scheme for persistence studies. Natural isolates from other clinical settings, including animal and environmental origin, will also be tested. The VAP model is in the framework of an H2020 ETN project called PRINT-AID. The aim of this project is to proof the value of developing a new generation of 3D-printed personalized medical devices with antimicrobial functionalities. Screening of new drug leads, in vitro testing in dynamic biofilm systems and cell models and improvement of the manufacturing process of 3D printed and coated catheters are currently being performed by collaborators. UAntwerp will be responsible for the development of a VAP mouse model in which the 3D produced tubes will be inserted in the main bronchus intratracheally. The tubes will be inoculated with biofilm-forming S. aureus and with this model we aim to evaluate the inhibition of bacterial adherence to the tubes in vivo and the anti-infective efficacy of the tubes by assessing the bacterial burden in the lungs.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The main goal of SPRINGBOARD project is to strengthen research potential of the Latvian Institute of Organic Synthesis (LIOS) through establishing long-lasting and sustainable collaboration network with the leading European research institutions – University of Antwerp, University of Copenhagen, University of Florence and University of Helsinki – in the area of advanced discovery and design of novel antibacterial drugs.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Augustyns Koen

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Additive manufacturing (AM) technologies have been extensively used in many fields and applications. Personalized medicine is one of the most promising fields that could benefit from such technologies. The Food and drug administration (FDA) approved in 2016 the first drug loaded device produced via AM introduced by Aprecia Pharmaceuticals. Fused filament fabrication (FFF) is one of the AM technologies that rely on the extrusion of a melted polymeric material through a nozzle. The consecutive movement in three-dimensional space while extruding material results in producing objects with high geometrical complexity. Such produced objects were not possible to build through conventional manufacturing technologies. This technology specifically has high potential in the pharmaceutical sector as it relies on a well-known technology used for producing drug loaded polymeric formulations, called hot melt extrusion (HME). In this technology a carrier polymer is mixed with a known active pharmaceutical ingredient (API) using a screw extrusion system and then hot extruded through a die for further processing. This project is a continuation of the PrintAID ITN-project. It aims at utilizing 3D-printing technologies for printing anti-infective medical devices. These devices should have the ability to prevent biofilm-related infections. Selected antibacterial agents will be analyzed for their thermal stability as the 3D printing process uses heat for processing. On the other hand, thermoplastic polymers will be investigated for their mechanical, rheological and thermal properties and the best ones will be selected as carrier for the antibacterial agents. The fused filament fabrication 3D printing technology will be modified and used to produce medical devices using the selected formulation. The modification will focus on reconfiguring the extrusion system to convert it from a conventional filament extruder to a pellet extruder, thereby providing more versatility in material selection. These devices will be analyzed in terms of mechanical integrity and formulation stability. in vitro and in vivo samples will be produced to study the release profile and the killing efficacy of the selected APIs. The intended goal is to produce proof-of-concept devices to tackle bacterial-associated infections on indwelling devices such as endotracheal tubes.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The project entitled "The Exploration of novel rapid technologies and alternatives to conventional microbiological test approaches" will explore new methodologies to replace conventional microbial quality testing methodologies.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This application relates to the purchase of new basic infrastructure, more specific a FlexiVent system from Emka Technologies. FlexiVent is a platform for standard respiratory research that can be used across many pulmonary applications and which has major advantages compared to the classical, non-invasive, unrestrained plethysmography because it is accurate, reproducible and proven. FlexiVent is much more capable of detecting pulmonary abnormalities via changes in functional residual capacity, total lung capacity, vital capacity, and compliance of the respiratory system. Furthermore, analysis of pulmonary functions via FlexiVent allows distinction between respiratory diseases in mice by clinically relevant variables and is therefore generally accepted as the standard in the functional evaluation of infectious and non-infectious pathological, respiratory disease models.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Delputte Peter
• Co-promoter: Verhulst Stijn

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Pulmonary infections caused by the Mycobacterium avium–intracellulare complex (MAC) are slow and progressive, and increasingly prevalent in developed countries. They can be cured, but their treatment consists of a 12 months multidrug regimen. A key issue standing in the way of designing more effective treatment regimens is the lack of a diagnostic tool for drug susceptibility testing (DST) in MAC. Current methods are slow (3-5 weeks), poorly reproducible and their results are difficult to interpret by clinicians. In this project, we will design a novel DST for MAC infections. It is based on the idea that a susceptible bug will feel stress under attack of an antibiotic, and a resistant one will not. The test is based on multiplex measurements of relative quantities of antibiotic-specific RNA biomarkers after short exposure to the drug. This test is unlike any test on the market. The project start fundamental, with transcriptional analyses of MAC cells under antibiotic stress. We will identify drug-specific sets of stress genes, and convert these into a Luminex-based format for multiplex quantification. The test parameters will be optimized using contemporary clinical strains, in collaboration with the National Reference Centre for Mycobacteria. Finally, we will apply our platform to identify synergetic interaction between novel and old compounds to derive optimal drug combinations with the strongest possible effect on clinical MAC strains.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Cappoen Davie
• Fellow: Sury Amandine

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Worldwide, pulmonary disease caused by members of the Mycobacterium avium complex (MAC) is increasing. Treatment of MAC lung disease requires a multidrug chemotherapy that takes up to 12 months and often leads to adverse drug effects, treatment failure, MAC reinfection and the emergence of drug resistance. New strategies need to be explored that can lead to more successful treatment of MAC infection. Mycothiol cysteine ligase (MshC) and the mycothione reductase (Mtr) are two key enzymes of the bacillary redox homeostasis and are unexploited drug targets. We hypothesize that these genes play an essential role for both the virulence and the stress tolerance within MAC and that targeting these genes would synergize with existing and emerging antimycobacterial therapeutics. In this project proposal we aim to investigate these hypotheses by the generation of a panel of recombinant MAC strains in order to study the impact of the target genes on the physiological growth, stress tolerance, cellular and in vivo virulence and synergy with existing and emerging MAC therapeutics. The findings can support future target-based drug development programs of potential Mtr and MshC inhibitors. In the long run, the findings within this research could lead to a safer, shorter and more cost-effective treatment of MAC infection.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Cappoen Davie
• Fellow: Piller Tatiana

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Black Soldier Fly Larvae (BSFL) are larvae from the insect the black soldier fly. They are currently being reared on a global industrial scale as a feed ingredient. They can be reared on a wide range of side and waste streams from food industry and agriculture, being converters of these streams into valuable biomass. Given the struggle of our food system to sustainably meet the protein demands of the growing world population, BSFL rearing offers an innovative, bio-based alternative contributing to a circular economy. As insect production is a novel branch of livestock production, it is up to (academic) researchers to gather the same level of in-depth knowledge that is available for other farm animals on production safety and optimization. For example, the impact of the chemical and microbial composition of the feed on the zootechnical performance and on the microbial safety of BSFL is virtually unknown. Furthermore, preliminary research points towards high value applications for other industrial sectors, such as the pharma and waste treatment sector, that could generate more profit for the insect production sector. This project aims to generate more fundamental knowledge that could support the insect sector, legislation and the co-emerging food value chain to remove legislative and technical hurdles in rearing and valorisation. More specifically, we will explore the hardly investigated interaction between the BSFL, their substrate and their gut microbiota. Such interactions are expected to depend on the substrate and affect (i) the growth of the larvae, (ii) their microbial safety, and (iii) their chemical safety. The overall goal of this project is to define and characterize a set of microorganisms that can be used to manipulate the gut microbiota of BSFL in order to boost its performance in each of the three aforementioned domains and increase their economic value.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand VLIR. UA provides VLIR research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

In this project, we will confirm the anti-inflammatory effects of Rothia mucilaginosa in complex and physiologically relevant in vitro models of CF and COPD lung inflammation, as well as in in vivo mouse models. The anti-inflammatory compound(s) produced by this bacterium will be identified and the mode of action unveiled.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains a major public health hazard throughout the world and was responsible for more than 1.7 million deaths in 2016.The prevalence of drug resistance in Mtb calls for the legitimization of new and highly specific drug targets, focusing on unique pathways.The project encompasses a multidisciplinary approach to disturb the redox homeostasis in Mtb, in an effort to uncover new drug leads for fighting this deadly infection.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Cappoen Davie
• Co-promoter: De Winter Hans

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UAntwerpen and on the other hand the client. UAntwerpen provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The European network for Integrated Training in Dry Eye Disease Drug Development (IT-DED3) aims to deliver multidisciplinary and entrepreneurial researchers trained to develop new therapies for patients suffering from dry eye diseases (DED). DED is a chronic, multifactorial disease of the ocular surface and is a major and increasing healthcare problem due to its high prevalence and economic burden because of the ageing population and frequent computer/tablet/smartphone usage. New DED drug development and translation from "bench to bedside" is urgently needed and therefore IT-DED3 integrates worldclass expertise in medicinal chemistry, process chemistry, ocular drug delivery and formulation, DED models, imaging, biomarker research and clinical ophthalmology. The scientific novelty is manifold, including new drug targets and compound classes, innovative formulation strategies for ocular drug delivery, and novel optical and molecular biomarkers identified by new imaging techniques and genomic-based systematic screening of a database of DED patients. The consortium of 7 beneficiaries and 10 partners (in total 7 from the non-academic sector) from 8 different European countries will select 12 early stage researchers (ESRs). Each ESR will perform high level scientific research in this stimulating multidisciplinary, international and intersectoral environment. Besides the scientific skills, the Personal Career Development Plan (PCDP) of each ESR will include transferable skills such as data management, project and time management, communication and dissemination, IP and valorisation. Both the research and training programme of IT-DED3 will deliver researchers with an enhanced career perspective and employability, who know how to use their entrepreneurial skills to move drug development projects in DED and other fields to the next technology readiness level.

Researcher(s)

• Promoter: Augustyns Koen
• Co-promoter: Cos Paul

Research team(s)

• Medicinal Chemistry (UAMC)

Project type(s)

• Research Project

Abstract

Leishmaniasis is a major neglected parasitic disease with a broad range of clinical manifestations including the lethal visceral disease. New drug discovery initiatives are essential given the serious adverse effects of current treatments and/or the increasing threat of drug resistance development. The present project aims to contribute towards novel concepts on intervention strategies that could bypass some problems relating to drug failure. Through the establishment of a sand fly colony, host-parasite interactions such as parasite virulence, disease-associated immunity and pathology, and treatment efficacy will be studied in laboratory rodent models that include the insect vector. The vector component will also allow improved antileishmanial lead characterization, drug resistance research and adaptation of clinical isolates to in vitro and in vivo laboratory models enabling improved monitoring of treatment efficacy in the field. This study will explore the interplay of host immune cells (neutrophils and monocytes) with recent clinical isolates and laboratory strains showing significant differences in virulence that arise from the acquisition of drug resistance. Responses will be studied by using a state-of-the art kinomics platform, that allows a straightforward acquisition of phenotypic fingerprints of intracellular kinase activation. This will provide cutting-edge information on the parasite-host interplay and on inflammation in general. Knowing that neutrophils have been ascribed infection-promoting activities, selective targeting of innate immune cell function will be explored as a complementary asset to control parasitic infections. This has not yet been explored, although anticipated to be much less prone to the development of resistance mechanisms. This approach could possibly also support the identification of novel drug or vaccine targets.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Caljon Guy
• Co-promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Treatment of tuberculosis is severely complicated by the adaptations of its etiological agent, Mycobacterium tuberculosis, allowing survival and replication within the host phagocytes. A better understanding of the host-pathogen interaction and the development of novel treatment strategies are thus critical. We strongly believe in a promising strategy involving the receptor-mediated delivery of therapeutics via the endocytic Sialoadhesin (Sn) receptor present on the surface of phagocytes.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Caljon Guy
• Co-promoter: Delputte Peter
• Fellow: Cappoen Davie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand VLIR. UA provides VLIR research results mentioned in the title of the project under the conditions as stipulated in this contract. The aim of the project is to set-up a center of scientific excellence in the Central-Eastern region of Cuba for traditionally used bioactive plants and their metabolites.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: De Winter Hans
• Co-promoter: Pieters Luc

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

According to ECDC, over 4 million healthcare-associated infections in the EU cause 37,000 deaths and cost EUR 7 billion/year. Half of them are related to medical devices (i.e., catheters, implants) and 80% of these are related to bacterial biofilms. A recent EC report highlighted the medical device sector's role in driving EU economic growth, employing 500k people in 25k companies (80% are SMEs) with annual sales of EUR 85 billion. The strategy to prevent medical device-infections is alteration of the device's surface with antimicrobials. However, current antimicrobial surfaces don't control bacterial growth in tissue surrounding implants, and only Sterilex® has received regulatory approval in the US as anti-biofilm agent. Participants in this proposal have earlier demonstrated a dramatic in vitro inhibition of biofilm formation by 3D-printing surfaces with antibiotics incorporated into the carrier polymers. This discovery opens new possibilities for printed medical devices that better resist biofilms. Our objective is to setup a new European education platform to guide and inspire young researchers in the intersectoral exploration of innovative routes to counteract microbial biofilms by fabricating anti-infective, tailored, 3D-printed medical devices. Current opportunities for young researchers to receive an structured, inter-sectoral and up-to-date education on personalized medicine and medical devices are marginal, and to our knowledge PRINT-AID is the first ETN set up for this purpose. State-of-the-art printing technologies will be combined with in vitro and in vivo biofilm models and novel tools for data integration/standardization. Doctoral training will be performed within a high-quality network of 12 participants (5 industrial) from the EU and US. It will include online and face-to-face courses taught by researchers with academic and industrial expertise in biofilms, 3D-printing research, antimicrobials, material science, and drug development.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Antibiotics have revolutionized medical practice against life-threatening infectious diseases. However, the evolution of antibiotic resistance currently poses a major threat to health-care, leading to worldwide increased morbidity and mortality. In addition to resistance, it is becoming clear that antibiotic therapy failure in many bacteria also results from a subset of cells that have switched to an antibiotic-tolerant "persister" state. Indeed, the survival of an antibiotic-sensitive bacterial population challenged with the lethal activity of antibiotics critically depends on the presence of this small fraction of non-growing, transiently antibiotic-tolerant cells. A recent study demonstrates that Escherichia coli persister levels can be very quickly tuned to the frequency of previous antibiotic encounters by genetic adaptation, leading to extreme levels of multidrug tolerant persisters when applying antibiotics daily. A similar rapid evolution of persistence was demonstrated in many important bacterial pathogens including urinary pathogenic E. coli and Burkholderia. Together, these results indicate that bacteria can genetically store information of past antibiotic treatments. We hypothesize that a similar evolutionary process may occur in vivo, thereby impeding successful clearance of the bacteria from the host. We will test this hypothesis by performing in vivo evolution experiments using urinary tract and lung infection models in mice.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

A strong anti-mycobacterial activity was found for a group of symmetrically substituted 1,3-diaryltriazenes. The compounds did not show genotoxicity and mutagenicity and the anti-mycobacterial activity was dependent on the substitution pattern. In this project we want to investigate (i) how the current lead compound can be optimized, (ii) if the compounds fulfill the WHO criteria and (iii) what the mechanism of action is of the 1,3-diaryltriazenes.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Cappoen Davie
• Fellow: Torfs Eveline

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This DnDi funded project relates to the preclinical evaluation of lead compounds with anti-parasitic activity for treatment of Leishmaniasis, Chagas disease and African trypanosomiasis. Compounds are also evaluated for cytotoxicity.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Cos Paul
• Co-promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

• Promoter: Augustyns Koen
• Co-promoter: Apers Sandra
• Co-promoter: Cos Paul
• Co-promoter: Delputte Peter
• Co-promoter: De Meester Ingrid
• Co-promoter: De Winter Hans
• Co-promoter: D'Haese Patrick
• Co-promoter: Hermans Nina
• Co-promoter: Kiekens Filip
• Co-promoter: Lambeir Anne-Marie
• Co-promoter: Maes Louis
• Co-promoter: Pieters Luc
• Co-promoter: Van Der Veken Pieter
• Fellow: Joossens Jurgen
• Fellow: Pauwels Maxim
• Fellow: Verhoeven Kristien

Research team(s)

• Medicinal Chemistry (UAMC)

Project type(s)

• Research Project

Abstract

(Mtb) are in high demand. In a past FWO project (G0020.10N) we synthesized and identified the class of octahydrobenzo[j]phenanthridinediones as promising antitubercular drug candidates. Ester analogs of the compound class showed a high degree of selectivity. For these compounds, we observed a sub-μM minimal inhibitory concentration against Mtb nearly 200 times lower than the 50% cytotoxic concentration against eukaryotic cells. However, the mechanism of action and the basis of selectivity remain unknown. Therefore, the general objective of this project is to study the mechanism of action of the octahydrobenzo[j]phenanthridinediones. We hypothesize a selective inhibition of mycothione reductase, a unique redox pathway in Actinobacteria, as the action mechanism. To this end,(i) we will identify the proposed target through genomic analysis of spontaneous Mtb mutants.(ii) We will validate the identified target through enzymatic and cellular approaches. (iii) In addition, we will study the activity against metabolically inactive bacilli and the synergism with existing TB drugs using state of the art models. This study will contribute to the fundamental understanding of the mechanism of action of the compound class and will add to the common knowledge on mycobacterial mycothione reductase. In the long term, the gathered knowledge could add to the development of new antitubercular drugs.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Abbaspour Tehrani Kourosch
• Fellow: Cappoen Davie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Our research focuses on resistance against the only oral drug miltefosine and will provide novel data to the field. Our results will not only be important to the parasitology field, but also to clinicians and public health professionals, supporting clinical decisions on future treatment policies, adequate diagnostic approaches and epidemiological resistance monitoring.

Researcher(s)

• Promoter: Caljon Guy
• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Co-promoter: Maes Louis
• Fellow: Eberhardt Eline

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The objective of our research is to determine whether the process of eNOS uncoupling can also be demonstrated in lung tissue after ischemia and reperfusion injury (IRI). In the first part of the project, experimental techniques were developed in order to detect free radical production during IRI using electron paramagnetic resonance. A murine model of pulmonary IRI was also developed. We are currently working on the effect of eNOS itself, and eNOS uncoupling, on free radical generation during pulkmonary IRI. Our final aim is to develop therapeutic strategies to tackle pulmonary IRI in patients undergoing complex surgery such as cardiopulmonary bypass, lung transplantation and isolated lung perfusion.

Researcher(s)

• Promoter: Van Schil Paul
• Co-promoter: Cos Paul
• Fellow: Gielis Jan

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Although good performance of solid state fermentation (SSF) on the lab scale, the industrial scale process has drawbacks, such as, poor heat transfer and difficult pH control. Bottleneck is the lack of information about the kinetics in SSF systems caused by the heterogeneous nature and complexity of the process. This project aims to model the kinetics of Monascus growth on rice based on experiments in a computer controlled solid state fermenter.

Researcher(s)

• Promoter: Cornet Iris
• Co-promoter: Apers Sandra
• Co-promoter: Cos Paul

Research team(s)

• Biochemical Wastewater Valorization & Engineering (BioWaVE)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between UA and CAPES (Brasil). UA provides CAPES research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Ocular Surface diseases (OSD) such as dry eye syndrome (DES) show an estimated prevalence between 15 and 29%. The only FDA approved and on subscription dry-eye treatment is cyclosporine 0.05% (Restasis®), but this formulation is not available in the EU. Novel therapies for OSD are therefore needed. The expertise within ADDN fosters a unique opportunity to set up a preclinical platform on OSD leading to an increased collaboration with industrial partners.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Augustyns Koen
• Co-promoter: De Meester Ingrid
• Co-promoter: Joossens Jurgen
• Co-promoter: Kiekens Filip
• Co-promoter: Lambeir Anne-Marie
• Co-promoter: Maes Louis
• Co-promoter: Van Der Veken Pieter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand VLIR. UA provides VLIR research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project aims to identify new mechanisms for the modulation of macrophages during activation of the immune system and during pathogen infections, using sialoadhesin, a macrophage-specific surface protein.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: Cos Paul
• Fellow: De Schryver Marjorie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Visceral leishmaniasis (VL) is caused by Leishmania donovani and L. infantum. Current drug therapies are associated with resistance, a high cost price, parenteral administration or serious side effects. Miltefosine (MIL) is the first oral drug against VL with a good therapeutic effect and ease of use and an acceptable safety profile. Recently, MIL was positioned as first-line therapy in India, Nepal and Bangladesh. However, MIL shows some characteristics that promote the emergence of resistance. The selection of MIL-resistant strains should be prevented and monitored, especially since there are no alternative drugs in clinical development. To proactively address the development of MIL-resistance, research on the resistance mechanisms and their cell biological and clinical implications is very important. This research project aims to obtain a standardized, clinically relevant laboratory model for the experimental induction of MIL-resistance. The MIL-resistant strains will be used to evaluate the effect of resistance on the MIL-uptake and parasite-cell interaction in Leishmania-infected macrophages. In addition, the fitness of the resistant strains will be assessed.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Fellow: Mondelaers Annelies

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the other hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The objective of our research is to determine whether the process of eNOS uncoupling can also be demonstrated in lung tissue after ischemia and reperfusion injury (IRI).

Researcher(s)

• Promoter: Van Schil Paul
• Co-promoter: Cos Paul
• Fellow: Gielis Jan

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Biofilm-related infections prove exceedingly difficult to treat because the organisms in a biofilm are protected from the circulating antimicrobials. Up till now, there have been relatively few studies investigating biofilm development in clinical isolates. Current in vitro methods for studying microbial adhesion and growth on biomaterial surfaces lack the influence of the host immune system, endorsing the specific need for animal models that allow temporal and spatial measurements based on non-invasive bio-imaging techniques using reporter strains. To improve our ability to prevent and/or treat biofilms, we need a better understanding of their formation and persistence. The specific goals of this research proposal are to i) understand the physiology of mono- and polymicrobial biofilms, with focus on staphylococci and Candida spp., isolated from indwelling devices from ICU patients and ii) implement in vitro and in vivo laboratory biofilm models that adequately reflect the real-life situation.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Goossens Herman
• Co-promoter: Maes Louis
• Co-promoter: Malhotra Surbhi
• Fellow: Kerstens Monique

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand EU. UA provides EU research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Van Cruchten Steven
• Co-promoter: Cos Paul

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

In this research project we will be investigating fundamental aspects related to the action of antibiotics against biofilms. In addition, in the long term our results could lead to the rational development of non-toxic agents that reduce the ability of biofilm cells to deal with ROS-related stress and could be used in combination with conventional bactericidal antibiotics.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Van Assche Tim

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The primary research aims of this project proposal are to unravel the dynamics and mechanisms of PMM and MIL resistance in L. donovani and L. infantum. To this end, our novel in vitro method for induction of drug resistance in amastigotes will enable to explore several aspects of PMM and MIL resistance prior to their routine use in the field. The deliverables of our study will contribute to the implementation of strategies/policies to avoid the appearance of drug resistance and assure the long-term efficacy of MIL and PMM.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand DNDI. UA provides DNDI research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Co-promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This is a fundamental research project financed by the Research Foundation - Flanders (FWO). The aim of this research community is to better understand the formation and the structure of bacterial and fungal biofilms in humans. This could lead to a more efficient treatment of biofilm-related infections.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Bacterial isolates from intensive care unit patients will be collected from urinary and intravascular catheters and endotracheal tubes. The biofilm phenotype in relation to antibiotic treatment failure will be investigated using molecular biological, bio-imaging techniques and in vitro and in vivo biofilm models. Particular emphasis will be given to Escherichia coli for urinary tract infections (UTI), Pseudomonas aeruginosa for ventilation associated pneumonia (VAP) and Staphylococcus aureus for systemic infections related to venous catheters. The acquired library of fully typed strains will enable in depth study of putative virulence factors that contribute to biofilm formation and treatment failure.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Co-promoter: Dewilde Sylvia
• Co-promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul
• Fellow: Clais Sofie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand Dafra. UA provides Dafra research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Biofilm-related infections prove exceedingly difficult to treat because the organisms in a biofilm are protected from the circulating antimicrobials. Up till now, there have been relatively few studies investigating biofilm development in clinical isolates. Current in vitro methods for studying microbial adhesion and growth on biomaterial surfaces lack the influence of the host immune system, endorsing the specific need for animal models that allow temporal and spatial measurements based on non-invasive bio-imaging techniques using reporter strains. To improve our ability to prevent and/or treat biofilms, we need a better understanding of their formation and persistence. The specific goals of this research proposal are to i) understand the physiology of mono- and polymicrobial biofilms, with focus on staphylococci and Candida spp., isolated from indwelling devices from ICU patients and ii) implement in vitro and in vivo laboratory biofilm models that adequately reflect the real-life situation.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Goossens Herman
• Co-promoter: Maes Louis
• Co-promoter: Malhotra Surbhi
• Fellow: Kerstens Monique

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Determination of drug susceptibility of Leishmania strains isolated from HIV co-infected patients using a combined approach of biological in vitro susceptibility testing (LMPH) and molecular biology tools.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The project focuses on some fundamental biological characteristics of an infection with the parasitic protozoa Giardia intestinalis, more in particular: 1/ mucosal interactions between the parasite and the host using in vitro and in vivo models and 2/ intestinal pathogenetic factors (virulence, infalmmation, motility, e.a.) that will affect the clinical outcome of the infection.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Fellow: Bénéré Ely

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The goal of this project is to gain insight in the role and applicability of virulence inhibitors in bacterial infections. The objectives are: 1. Development of an in vitro multi-species biofilm model with P.gingivalis. 2. Development of an in vitro virulence model for P. gingivalis-mediated collagen degradation. 3. Development of P.gingivalis animal model. 4. Evaluation of virulence inhibitors in bacterial in vitro and in vivo models.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The goal of this project is to gain insight in the role and applicability of protease (DPP4) inhibitors in bacterial infections. The proof-of-concept will be obtained in Porphyromonas gingivalis models with the following objectives and work packages: 1. Development of in vitro and in vivo virulence models for P. gingivalis. 2. Evaluation of enzyme inhibitors using purified recombinant P. gingivalis DPP4. 3. Evaluation of DPP/protease inhibitors in bacterial in vitro and in vivo models. 4. SAR and optimisation of the lead compounds. 5. Biochemical characterisation of lead compound-target enzyme interactions.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Augustyns Koen
• Co-promoter: Lambeir Anne-Marie
• Co-promoter: Maes Louis
• Co-promoter: Van Der Veken Pieter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The specific objectives of this research proposal are: ¿ Optimisation and validation of EPR analysis for ex vivo quantification and identification of free radicals in macrophages. ¿ Determining the role of oxidative stress in the survival of the Leishmania parasite in the macrophage. ¿ Studying the link between oxidative stress and the action of current (antimonials) and new (PX-6518) antileishmanial compounds.

Researcher(s)

• Promoter: Maes Louis
• Fellow: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The objective of the research is to obtain a series of well characterized fractions enriched in MFGM-glycoproteins with a high potential for anti-H.pylori action, due to their anti-adhesion and/or antimicrobial effects. In addition, these fractions will be checked for resistance towards gastro-intestinal digestion, and, in case of low digestibility, for possible effects on the composition and bioactivity of the microbiota in the large intestine.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The project contains field research in the context of the ongoing activity profiling of PX-6518 against cutaneous Leishmania species. Primary objectives are to obtain insight and experience in New-World leishmaniasis and to transfer validated in vitro laboratory Leishmania models between the North and the South partner. The action of the new antileishmania lead compound PX-6518 against recently collected Peruvian field CL-strains will be further studied within a collaboration between the UA-LMPH and the University at Lima, Peru.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

A new research initiative will study the micro-aerophilic intestinal protozoa Giardia intestinalis. This pathogen has developed anti-oxidative defense mechanisms to withstand the oxygen tension in tissues and organs, e.g. via oxidation of cellular thiols, superoxide-dismutase and possibly other mechanisms. The importance of these mechanisms is illustrated by the fact that current therapeutics (nitro-compounds) exert their action via selective increase of oxidative stress. The research plan involves the following steps: 1. development/optimization of in vitro culture method for trophozoites 2. establishment of conditions for induction of cyst formation, 3. development of a suitable laboratory animal model, 4. influence of oxidative stress on the in vitro and in vivo survival by in situ quantification of oxidative/antioxidative phenomena 5. evaluation of new molecules in the in vitro and in vivo models 6. evaluation of disinfectants for inactivation of cysts in drinking water 7. interaction of the parasite with intestinal lining (pathology, inflammation, e.a..)

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Adriaensen Dirk
• Co-promoter: Cos Paul
• Fellow: Bénéré Ely

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

For most infectious diseases, chemotherapeutics are still required for disease control as vaccines are generally lacking. In addition, drug resistance has become a critical issue, which endorses the need for continuous drug research. LMPH is actively involved in the identification of new synthetic and natural lead compounds, with a particular focus on the tropical protozoal diseases Leishmaniasis, sleeping sickness, Chagas disease and malaria. Validated in vitro and in vivo test systems and drug screening technologies have been developed. The Drugs for Neglected Diseases Initiative (DNDi) has access to compound libraries which have never been tested for the listed diseases. In this project, both groups have joined expertise and know-how to achieve a more productive drug discovery platform.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Co-promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

A biofilm is defined as a microbially-derived sessile or adherent community embedded in a matrix and irreversibly attached to a surface. Since biofilms exhibit a high resistance against biocides, this project will develop a method to detect Staphylococcus aureus biofilms. In addition, several known and new biocides will be evaluated for their capacity to inhibit biofilm growth or to destroy existing biofilms.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The University of Antwerp (UA) and the Institute of Tropical Medicine Antwerp (IMTA) together with the pharmaceutical industry partner Tibotec have agreed to collaborate in lead-finding and lead-exploration for tropical & neglected diseases, such as malaria, leishmaniasis, sleeping sickness and Chagas disease. Practically, a test battery for medium throughput in vitro drug evaluation will be set up on the basis of the joint technical know-how to accommodate, among others, for the current screening needs by WHO-TDR. Compound (chemicals and natural products) acquisition through existing networks will continue and dedicated compound-handling logistics will be implemented. As a secondary objective, capacity will be created to assess `drug developability' through early pharmacological and pre-clinical profiling of selected `hits'. This project focuses on tropical diseases that remain of prime interest to WHO-TDR and offers realistic possibilities of identifying new leads.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

In this research antiviral and antioxidant compounds will be isolated from medicinal plants in order to develop a complementary therapeutical strategy against HSV- and HIV-infections.

Researcher(s)

• Promoter: Vlietinck Arnold
• Fellow: Cos Paul

Research team(s)

Project type(s)

• Research Project