Research Surbhi Malhotra

Abstract

Colorectal cancer (CRC) is the third commonly diagnosed cancer and fourth cause of cancer death worldwide. An altered microbiome, also known as dysbiosis, can often be seen in CRC patients. Radiotherapy and immunotherapy are known treatment options for colorectal cancer, but are associated with toxicity and heterogeneous responses, respectively. Fecal microbiotal transplantation (FMT) has been shown to reduce radiation-induced toxicity and dysbiosis in mice and improve immunotherapy responsiveness in patients. To date, FMT has never been introduced with the dual therapy of radiotherapy and immunotherapy. Therefore, it is not clear whether this combined treatment will result in improved treatment outcome, lesser side-effects, tumor burden etc. In this project, we first intend to characterize the effects of dual radiotherapy and immunotherapy using the well-established azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC mouse model. CRC mice will be treated with radiotherapy, immunotherapy or dual radiotherapy and immunotherapy, after which diagnostic microbial biomarkers for immunotherapy responsiveness and predictive microbial biomarkers of treatment outcome will be determined. Additionally, we plan to study if and how FMT can tackle radiation-induced dysbiosis and immunotherapy efficiency. Throughout the experiment, fecal samples will be collected and used to perform 16S microbial profiling. Tumor load (number, size, area), histo-pathological analysis (e.g. stem cell proliferation, apoptosis, mucus formation), inflammatory/immunological markers and proteomics analysis will be performed and correlated with the microbial dynamics to identify predictive and diagnostic biomarkers for treatment outcome and side-effects. Additionally, flow cytometry analysis, stainings and protein quantification assays for tight junctions will be used to assess bacterial translocation. FMT will be introduced in an anaerobic bag and similar experiments as explained above will be performed to determine if FMT can improve treatment outcome and side-effects. Meta-proteomics and meta-transcriptomics will be performed and will be integrated in an integrative omics analysis with the metagenomics to help understand the functional involvement of FMT in improving treatment outcome and side-effects.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Kumar-Singh Samir

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Respiratory tract infections (RTIs) are one of the most common causes of mortality and morbidity among infectious diseases worldwide. However, the aetiology of RTIs is often undiagnosed due to the complicated presence of a myriad of bacterial, viral and fungal pathogens and opportunistic microorganisms in the complex respiratory microbiome. Moreover, RTI diagnosis is challenged by the current limitations of conventional culture-based tests and hypothesis-based narrow-spectrum molecular tests. With the causative pathogens often unknown at the time of treatment, not surprisingly, RTIs account for a high antibiotic consumption rate where most of the antibiotic prescriptions are empirical, especially for critical patients in intensive care units (ICUs). Accordingly, patients are exposed to the risks of antibiotic overtreatment, adverse effects and complications such as Clostridium difficile infections. In addition, empiric treatments with broad-spectrum antibiotics can promote the selection and dissemination of multidrug-resistant pathogens. Thus, a rapid and accurate microbiological diagnosis could prevent inadvertent antibiotic prescription or allow a timely switch to the required targeted antibacterial therapy. In this respect, metagenomics next-generation sequencing (mNGS), and more specifically long-read sequencing, has been speculated to offer enhanced diagnostic capabilities by providing a culture-independent, hypothesis-free all-in-one assay for pathogen identification in RTI diagnostics. Despite these advantages demonstrated by a number of proof-of-concept studies, applying metagenomics into clinical diagnosis is challenging, particularly for respiratory samples (such as bronchoalveolar lavage – BAL, endotracheal aspirate – ETA, sputum) due to the abundant presence of commensal flora, extracellular DNA and human host DNA. In this project, we aim to utilise state-of-the-art nanopore long-read sequencing to develop a complete, rapid mNGS workflow integrated into a point-of-care (POC) set-up to enable a one-step RTI diagnosis directly from respiratory samples. The designed workflow includes a patentable standardised method, "disclosure method A", for processing respiratory samples developed to overcome the sample-bound difficulties of high host DNA. In this workflow, we will also develop a bioinformatics pipeline method, "disclosure method B", for sequencing result analysis that can be protected with copyright. We also aim to evaluate the feasibility and demonstrate the superiority of this workflow and developed methods over conventional culture-based and molecular methods in terms of sensitivity, specificity, turn-around-time, and cost-effectiveness.

Researcher(s)

• Promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Variants of concern (VoC) of SARS-CoV-2 raise the possibility of increases in transmissibility, severity and immune evasion. Children and pregnant women who have not been prioritised in the pandemic, are likely to be the last population for whom vaccines are approved and may have low uptake, increasing the risk of VoC arising in this population. Monitoring this group across regions is crucial given rapid changes in epidemiology due to interventions, vaccine rollout and viral evolution. VERDI (SARS-CoV-2 variants Evaluation in pRegnancy and paeDIatrics cohorts) will build on a long-standing infectious disease research and trial network (Penta) to address research questions on the impact of VoC in these vulnerable groups. VERDI's objectives are: i) track and characterise VoC in paediatric and pregnant populations across the globe; ii) understand effects of VoC on clinical outcomes (short/longer term), vaccine effectiveness and transmission characteristics; iii) model outcomes and impacts of VoC; iv) develop evidence-based recommendations for control of COVID-19. VERDI will achieve these objectives by bringing together a diverse range of cohort studies including large scale national and regional level population-based cohort studies from the EU and beyond, providing a unique opportunity for harmonised analysis of data on VoC from a range of sources (e.g. electronic health records, bespoke cohort studies, household transmission studies, screening programmes). We will facilitate expansion of existing studies, e.g. replicating ongoing European household studies elsewhere. Through this approach, VERDI will expand and enhance existing cohort networks, including promoting flexibility to adapt to future emerging infections. The project will improve understanding of the epidemiology and impact of VoC, leading to robust recommendations for control in a range of global settings as well as developing preparedness for future health emergencies.

Researcher(s)

• Promoter: Goossens Herman
• Promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Around 10% of newborns in Europe will be admitted to a neonatal intensive care unit (NICU). Critically ill babies are a highly vulnerable population for the acquisition of resistant bacteria. Sepsis is among the most common events in NICU and is known to be associated with high mortality and poor long-term outcomes. Despite rising awareness of high rates of resistant bacterial colonisation reported in NICU, there is very little robust specific data on globally applicable infection prevention and control (IPC) measures. NeoIPC focuses on new approaches to the prevention and management of resistant bacterial colonization and infection on NICU. The project builds on and further extends the collaboration between 13 partners with a proven track record in relevant areas, including neonatal infection, IPC, implementation science, microbiology and surveillance. NeoIPC aims to develop and implement an innovative approach towards the evaluation of IPC interventions combining a robust cost-efficient randomised trial combined with the evaluation of a suitable implementation science strategy and novel targeted clinical and genotypic surveillance. A further goal is to generate widely relevant pan-European network strategies to improve IPC in routine neonatal care. This will be achieved through six interrelated work packages to deliver a cluster randomised trialimplementation hybrid investigating the impact of skin antisepsis on infant hospital-acquired clinical sepsis and resistant bacterial colonisation, coupled with a comprehensive implementation strategy incorporating optimal targeted surveillance in a clinical network with tailored dissemination and exploitation to facilitate sustainable embedding of outputs. NeoIPC will generate globally transferrable outputs to reduce hospital transmission of resistant pathogens, foster and facilitate collaborative research and IPC implementation efforts with a broad and long-lasting impact for critically ill newborns and infants.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman
• Co-promoter: Hens Niel

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

The ongoing COVID-19 pandemic creates an unprecedented burden worldwide. Vaccine-induced immunity is the only promising solution. There is continued need for phase 2 & 3 vaccine trials to reach long-term, large-scale immunity of the entire European population. VACCELERATE will be the pan-European backbone accelerating phase 2 & 3 COVID-19 vaccine trials. The overall objective of VACCELERATE is to connect all European stakeholders involved in vaccine development to provide a pan-European platform for clinical trial design and conduct. VACCELERATE constitutes the rapid response single entry-point to stakeholders from public health authorities to vaccine developers, to address respective needs and kickstart specifically phase 2 & 3 vaccine trials. VACCELERATE conducts capacity mapping of clinical trial and laboratory sites to identify suitable sites for individual phase 2 & 3 vaccine trials. Capacity building via training will increase quality in sites across Europe. Volunteer registries facilitate patient recruitment. Access to laboratory sites and a standardised set of assays essential for clinical phase 2 & 3 trials is provided. A harmonised European approach to vaccine trials is enabled by aligning educational standards, coordination of laboratory support and providing standardised assays and trial protocols. Harmonised data collection, open data sharing and pooling of data for stronger analysis enables data standardisation. VACCELERATE offers solutions for characteristic vaccine development issues during pandemics by closing gaps in public health knowledge and improving knowledge transfer. VACCELERATE amalgamates the vast but scattered expertise across Europe into one network to deliver strategic scientific leadership and guidance on vaccine trials in Europe. Beyond the COVID-19 pandemic, it will be an established pandemic preparedness network, ready to face emerging future pandemics, as well as a pivot in Europe?s capacity to develop vaccines.

Researcher(s)

• Promoter: Goossens Herman
• Promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

VAXINFECTIO-PD is an established Industrial Research Fund (IOF) consortium, well equipped to build an ecosystem offering research, valorisation, innovation and development to answer existing and new challenges in the field of infectious diseases and vaccinology. These domains fall within one of the valorisation domains of the Antwerp University, and the newly established business unit Antwerp Valorisation & Development (AVD) of the UAntwerp. The VAXINFECTIO-PD consortium built up a unique and extensive track record through research, services, spin-off creation and innovative pathways, in generating product concepts/prototypes and research platforms that form the basis of medical innovation. The various core research units have had an important international image in the recent years with publications in leading journals, coordination of several European projects, as well as active presence and involvement in international scientific and policy forums. For the 6-year period the IOF-consortium will further focus on 5 interlinked valorisation avenues, all creating or guaranteeing growth on the parameters P3, P4, P5 and P6: translational vaccination platform for improved and new preventive and therapeutic vaccines, prognostic and diagnostic platforms, core facilities (for cellular vaccines, human challenge studies and biobanks), infectious disease and immune modelling and prediction, and improved vaccine delivery and medical devices through product development.

Researcher(s)

• Promoter: Van Damme Pierre
• Promoter: Vorsters Alex
• Co-promoter: Beutels Philippe
• Co-promoter: Cools Nathalie
• Co-promoter: Hens Niel
• Co-promoter: Lion Eva
• Co-promoter: Malhotra Surbhi
• Co-promoter: Van Damme Pierre
• Co-promoter: Verwulgen Stijn
• Co-promoter: Vorsters Alex
• Fellow: Bamberger Martina

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

The general objective of this research community is to better understand the origin and structure of bacterial and fungal biofilms in humans so that effective action can be taken against them in the long term.

Researcher(s)

• Promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Goals of PediCAP are Fill the knowledge gaps on antibiotic therapy of community-acquired pneumonia in pediatric age, in terms of optimal duration, oral step-down schedule evaluating effectiveness, safety and selection of antimicrobial resistance. Evaluate economic impact of antibiotic therapy in terms of cost-effectiveness. Implement the infrastructure that links study sites in order to share knowledge, develop study specific and general research skill straining programme and promote capacity development initiatives.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

The ORCHESTRA project provides an innovative approach to learn from the SARS-CoV-2 health crisis and derive recommendations for increasing preparedness for future outbreaks. The main outcome of the project is the creation of a new pan-European cohort built on existing and new large-scale population cohorts in European and non-European countries. ORCHESTRA aims to perform in-depth laboratory based assays on samples collected from Covid-19 patients during acute phase and during long-term sequelae as well as follow-up individuals post-vaccination. University of Antwerp laboratories are studying viral variants and the respiratory microbiome dynamics (Surbhi Malhotra) as well as analyzing the humoral and cell-mediated immune responses and cytokinome profiles (Samir Kumar -Singh). The laboratory analysis workpackage also aims to understand the role of human genetics, epigenetics and of the gut microbiome in disease pathogenesis and prognosis. This large consolidated wet-lab WP is led by the University of Antwerp. The project is funded by the European Union's Horizon 2020 research and innovation programme under the ERAvsCORONA Action Plan developed jointly by Commission services and national authorities.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Kumar-Singh Samir

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

The ORCHESTRA project provides an innovative approach to learn from the SARS-CoV-2 health crisis and derive recommendations for increasing preparedness for future outbreaks. The main outcome of the project is the creation of a new pan-European cohort built on existing and new large-scale population cohorts in European and non-European countries. Data analysis through a federated learning technique supported by advanced modelling capabilities will allow the integration of epidemiological, clinical, microbiological and genotypic aspects of population-based cohorts with environment and socio-economic features. The ORCHESTRA cohort will include SARS-CoV-2 infected and non-infected individuals of all ages and conditions and thereby enabling a retrospective evaluation of risk factors for the disease acquisition and progression of the disease and prospective follow-up aimed at exploring longterm consequences and analysis of vaccination response when vaccines will be available. To better address these research questions, the ORCHESTRA-cohort will include adequately sampled representatives of general populations, COVID-19 patients and special 'at risk' populations of fragile individuals and health-care workers. The project will assess also health costs of COVID-19 with special emphasis on delayed health services in the fragile populations. The participation of non-European and Low-Medium Income Countries and a Global COVID-19 Guidance group of major stakeholders and investigators from successful clinical trials addressing therapeutic approaches to COVID-19, ensures inclusion of all expertise needed and translation of recommendations to different social and economic settings. The project will significantly impact on the responsiveness to SARS-CoV-2 and can be used as a model for responsiveness for new public health threats. Specifically, in this work package, different cytokines and chemokines from blood of COVID-19 patients will be studied and markers predicting disease severity, mortality, and/or long term sequalae will be identified in collaboration with other partners of ORCHESTRA.

Researcher(s)

• Promoter: Kumar-Singh Samir
• Co-promoter: Malhotra Surbhi

Research team(s)

• Laboratory of cell biology and histology

Project type(s)

• Research Project

Abstract

Infection with SARS-CoV-2 mostly leads to a mild self-limiting respiratory tract illness, however, some patients develop severe progressive pneumonia, multiorgan failure, and death. This project aims to determine factors that dictate the course of COVID19 beyond cytokines. We have prior data that specific aberrantly expressed mucins, triggered by SARS-CoV-2, regulate ACE2 expression and affect lung barrier integrity. Such mucin alterations are clinically relevant as excessive mucin production is seen in severe COVID-19 illness obstructing the respiratory tract and complicating recovery. Here, we will first identify differentially expressed mucin isoforms in COVID-19 patients exhibiting the entire spectrum of disease severity. Thereafter, therapeutics currently used for COVID-19 will be screened for their ability to reduce mucin abundance. As mucin expression is also a critical factor in microbiome homeostasis and dysbiosis might modulate COVID-19 severity, this project secondly aims to map the microbiome associated with different degrees of disease severity. Unravelling mucin isoform-microbiome interactions that shape the course of SARS-CoV-2 infection will lead to the future identification of those patients who are in danger of progressing to severe disease. This project will also improve the choice for an appropriate treatment as well as the time frame of treatment options once infection occurs.

Researcher(s)

• Promoter: De Winter Benedicte
• Co-promoter: Malhotra Surbhi
• Co-promoter: Smet Annemieke
• Co-promoter: Verstraeten Aline

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

Antimicrobial resistance (AMR) is on the rise, resulting in 700 000 deaths worldwide every year. In Croatia and Hungary, AMR is responsible for the rapid increase in morbidity and mortality rates. The EU-funded AmReSu project will strengthen the innovation capacity in AMR surveillance in both countries, focussing on whole genome sequencing in correlation with next-generation sequencing techniques. It will also establish an "AMR surveillance vision." The project relies on the cooperation of Semmelweis University in Budapest and Klinika za infektivne bolesti "Dr. Fran Mihaljevic" in Zagreb with two internationally leading research institutions, the Laboratory of Medical Microbiology at the University of Antwerp and the Health Research Institute of the Balearic Islands. AmReSu will facilitate knowledge transfer, exchanges of best practices via training activities and the promotion of research excellence.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Infection with SARS-CoV-2 mostly leads to a mild self-limiting respiratory tract illness, however, some patients progress to develop severe progressive pneumonia, multiorgan failure, and death. The project aims to determine factors that dictate the severity of COVID-19. Firstly, guided by our prior data of interaction of certain mucins with the ACE2 receptor and the clinical evidence of excessive mucin production in severe COVID-19 illness, we intend to characterize different mucins for their role in both the initiation and progression of COVID-19. Secondly, based on a severe degree of edematous interstitial lung tissue pathology observed in COVID-19 autopsies and its hypothesized link to abnormally low PaO2 observed clinically, the project intends to characterize aquaporin (AQP) water channels that are responsible for fluid transport across cells. This has important therapeutic relevance for COVID-19 as specific AQP inhibitors have been shown to attenuate inflammation and lung injury and to block mucin hypersecretion. Lastly, mucin expression is also a critical factor in microbiome homeostasis and based on, so far, scarce data that co-infection with other respiratory pathogens and other microbial interactions might modulate COVID-19 severity, the project aims to characterize the microbiome associated with different degrees of disease severity. Identifying factors that shape the course of SARS-CoV-2 infection will lead to identification of plausible targets to treat COVID-19.

Researcher(s)

• Promoter: De Winter Benedicte
• Co-promoter: Jorens Philippe
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Malhotra Surbhi
• Co-promoter: Smet Annemieke
• Co-promoter: Verstraeten Aline

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

CAP-IT is a multicenter randomized double-blind 2x2 factorial noninferiority trial investigating the efficacy, safety and impact on antimicrobial resistance of amoxicillin administered as a shorter or longer course at a lower or higher dose for uncomplicated childhood pneumonia. The analysis at the University of Antwerp (UA) will comprise two parts: (i) research on S. pneumoniae colonization with respect to circulating (vaccine) serotypes in the UK and pneumococcal penicillin resistance; and (ii) evaluation of the microbial communities present in the respiratory tract of patients to identify and quantify the microbial shift as well as changes in the presence of antimicrobial resistance genes related to the effect of the different durations and doses of amoxicillin administered in CAP-IT. These data will be generated using metagenomics and metatranscriptomic sequencing using both PacBio and Illumina technologies.

Researcher(s)

• Promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Clostridioides difficile constitutes the main source of healthcare-associated infectious diarrhea across the globe, causing a disease known as C. difficile infection (CDI) associated with prolonged hospital stay and increased mortality. Whole-genome sequencing (WGS) approaches applied to the study of C. difficile have revealed a highly variable 4.1-4.3 Mb genome that is not only rich in mobile genetic elements but is also highly complex to assemble due to the presence of numerous repeat regions. Thus, conventional short-read sequencing technologies have had limited success in resolving C. difficile genomes and have led to incomplete, and incorrectly assembled genomes. In this study, we intend to employ single-molecule real-time (SMRT) long-read sequencing to obtain complete, gapless C. difficile genomes and enable a high-resolution genome-wide analysis and comparison of clinical reference strains isolated from patients across Europe contained in the ECDC/Leeds-Leiden reference collection. This sequenced collection will be made publicly available in the European Nucleotide Archive (ENA)/NCBI to stimulate further research on different aspects, both fundamental and clinical, of CDI with the aim of developing better preventive, therapeutic/diagnostic, and typing strategies.

Researcher(s)

• Promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Colistin (CL) is a last line antibiotic used to treat hospital-associated infections due to multi- and extremely-drug resistant Gram-negative bacterial pathogens, and also in veterinary medicine to treat post-weaning diarrhoea in food animals. Increasing use has led to the emergence of both chromosomal and transferable plasmid-mediated (mcr) colistin resistance in pathogens. While the chromosomal mechanisms involve mutations in several genes, which also modify the bacterial metabolic pathways, the mcr-mediated mechanism confers low-level colistin resistance, and its role, relevance and fate in mediating colistin resistance in human pathogens remain to be explored. Another phenomenon that remains to be understood is of heteroresistance wherein bacterial subpopulations exhibit different susceptibilities to colistin and can lead to treatment failures during infection. Recent advances in next-generation sequencing have made it possible to study the genome and gene expression at the single cell level. In this project, we intend to study the complexities of resistance and heteroresistance evolution in a population utilizing whole genome sequencing and beyond state of the art NGS techniques of single-cell sequencing and gene expression analysis on pathogenic bacteria, Klebsiella pneumoniae and E. coli, evoluted in vitro under colistin pressure as well as in a mouse model of infection and finally in respiratory samples from patients treated with colistin.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Xavier Basil Britto
• Fellow: Rajakani Sahaya Glingston

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Infectious diseases (ID) and antimicrobial resistance (AMR) pose a continuous and serious threat to humans and animals (One Health). Five research units from the UAntwerpen, with strong international records and collaboration, will continue to jointly capitalize on their ID expertise. EVECO studies distribution, evolution and ecology of pathogens (plague, arenaviruses, …) and wildlife hosts, offering insights for emerging ID management. LMM has established large consortia (COMBACTE, PREPARE) leading to pan-European infrastructures for ID and antimicrobial consumption research. Next to developing rapid diagnostics, LMM investigates AMR mechanisms and pathogen dynamics in vitro, in humans/livestock, and in animal models to study host-immune response (biomarker discovery) and bacterial pathogenicity. LEH performs cutting-edge research on cell-based immunotherapies, in collaboration with the UZA Center for Cell Therapy & Regenerative Medicine. LEH investigates host-immune responses in vaccine trials using multi-parametric flow cytometry and systems biology to discover novel immune correlates of protection in next-generation vaccines. CEV studies the epidemiology of vaccine-preventable diseases and performs state-of-the-art vaccine trials with large national/international networks, including maternal immunization trials and quarantine studies with genetically-modified polioviruses. Given the global need for EID vaccines (Lassa, Ebola, …) , CEV engages in several innovative (non)-human challenge-phase 1-2 studies. CHERMID undertakes methodological and applied research on the intersection between health economics, biomedicine and mathematics. CHERMID is internationally renowned for developing models of dynamic ID processes within and between hosts and integrating these with cutting edge economic models. By integrating these complementary expertises, this COE will address current and future challenges in ID management.

Researcher(s)

• Promoter: Van Damme Pierre
• Co-promoter: Beutels Philippe
• Co-promoter: Leirs Herwig
• Co-promoter: Malhotra Surbhi
• Co-promoter: Van Tendeloo Vigor

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

Antimicrobial resistance (AMR) is of great public health concern, causing numerous losses of lives worldwide and threatening to reverse many of the considerable strides modern medicine has made over the last century. There is a need to stratify antibiotic and alternative treatments in terms of the actual benefit for the patient, improving patient outcome and limit the impact on AMR. High quality, effective and appropriate diagnostic tests to steer appropriate use of antibiotics are available. However, implementation of these tests into daily healthcare practice is hampered due to lack of insight in the medical, technological and health economical value and limited knowledge about psychosocial, ethical, regulatory and organisational barriers to their implementation into clinical practice. VALUE-Dx will define and understand these value indicators and barriers to adoption of diagnostics of Community-Acquired Acute Respiratory Tract Infections (CA-ARTI) in order to develop and improve health economic models to generate insight in the whole value of diagnostics and develop policy and regulatory recommendations. In addition, efficient clinical algorithms and user requirement specifications of tests will be developed fuelling the medical and technological value of CA-ARTI diagnostics. The value of diagnostics will be tested and demonstrated in a unique pan-European clinical and laboratory research infrastructure allowing for innovative adaptive trial designs to evaluate novel CA-ARTI diagnostics. Close and continuous interaction with the VALUE-Dx multi-stakeholder platform provides for optimal alignment of VALUE-Dx activities with stakeholder opinions, expert knowledge and interests. A variety of dissemination and advocacy measures will promote wide-spread adoption of clinical and cost-effective innovative diagnostics to achieve more personalized, evidence-based antibiotic prescription in order to transform clinical practice, improve patient outcomes and combat AMR.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Coenen Samuel
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

New interventions are required to prevent the emergence of antimicrobial resistance in contemporary sexually transmitted infection (STI) epidemics in men who have sex with men (MSM). Here, we perform a double-blinded single centre, crossover, randomized controlled trial of antibacterial vs. placebo mouthwash to study reduction in incidence of gonorrhoea/chlamydia/syphilis in MSM taking preexposure prophylaxis.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Hens Niel

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Colorectal cancer (CRC) is the second most common malignancy in the world. With an estimated recurrence rate of 20-30%, CRC represents an important health and socioeconomical burden. Recent data based on metagenomics and experimental models suggest a strong contribution of the gut microbiome in modulating CRC development. This project aims to understand the role of microbiome in CRC development and recurrence, specifically in studying if CRC recurrence is significantly affected by the radiation induced dysbiosis and if faecal microbiota transplantation can resolve radiation-induced dysbiosis and attenuate CRC development.

Researcher(s)

• Promoter: Kumar-Singh Samir
• Co-promoter: Malhotra Surbhi
• Fellow: Wouters Shari

Research team(s)

• Laboratory of cell biology and histology

Project type(s)

• Research Project

Abstract

General use of vaccines against Streptococcus pneumoniae (S. pneumoniae) in infants has led to a decrease in the presence of the serotypes against which the vaccine was developed. It is a pathogen of which more than 90 different serotypes exist, of whom 10 to 13 are covered by the current vaccines. In order to gain a clear understanding of the S. pneumoniae serotypes carried by infants, and the impact of the vaccine used in the vaccination program, the current study was set up. As early as the first months of our lives S. pneumoniae is present in the nasal cavity and in the pharynx, mostly only temporary and innocuous, yet in some cases, in infants it may lead to infections such as otitis, pneumonia or meningitis. Since the presence of S. pneumoniae is more abundant in some circumstances, the current study focuses on infants between the age of 6 and 30 months either healthy and residing in day-care centres or suffering from an acute middle ear infection. Over a 4 year period, a swab will be taken from the nasal cavity of these infants (700 in first year, 900 in subsequent years, 6800 in total) to investigate presence, density and type of S. pneumoniae carriage, if any, as well as its resistance against antibiotics. The presence of some other pathogens that can cause airway or ear infections will be investigated too. The findings of this study will be extremely valuable to guide decisions on vaccine development, vaccine program, and recommendations on antibiotic treatment.

Researcher(s)

• Promoter: Van Damme Pierre
• Co-promoter: Malhotra Surbhi
• Co-promoter: Theeten Heidi
• Fellow: Wouters Ine

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

This project aims to advance the currently available sequencing technologies at the University of Antwerp (UA) by acquiring a third generation sequencing (3GS) platform. The flagship of the third generation, single-molecule longread sequencers, PacBio Sequel, harnesses the natural process of DNA replication and enables real-time observation of DNA synthesis. 3GS promises to open new avenues for sequencing-based research beyond the current state-of-the-art for this consortium, which consists of more than 14 UA research groups in various disciplines of medicine, biology and bioinformatics. Furthermore, several third parties have also committed to utilize this technology for their ongoing and future research studies. 3GS will be utilized by this consortium to (i) sequence prokaryotic and eukaryotic genomes, and difficult-to-sequence genome regions, (ii) identify new genes and mutations in various rare Mendelian disorders, (iii) identify epigenetic modifications to better understand biological processes like gene expression and host-pathogen interactions, (iv) precisely profile the human, murine, and environmental microbiome in disease and under various environmental stressors, and (v) develop novel preventive therapies for infection-prone disorders for better drug targeting. The analysis of the large amount of genomic and transcriptomic data generated by the various research groups will be coordinated by the UZA/UA bioinformatics group Biomina.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Laukens Kris
• Co-promoter: Mortier Geert
• Co-promoter: Smet Annemieke
• Co-promoter: Vanden Berghe Wim
• Co-promoter: Van Rie Annelies

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Since two decades, methicillin-resistant Staphylococcus aureus (MRSA) has become a major cause of medical device-associated and postsurgical wound infections in hospitals and of pneumonia in the community. In these infections, MRSA favors the biofilm phenotype, living in a community encased in an extracellular matrix that affords protection against the host immune system and antibiotics, making these infections recalcitrant to treatment. Our laboratory has shown that two highly pathogenic and globally successful MRSA clones, USA300 and EMRSA-15, are prolific biofilm formers. Interestingly, our transcriptomics data has revealed spectacularly different mechanisms of biofilm formation between these two clones. For instance, in USA300-S391 biofilms, Hfq, a global regulator of small non-coding RNAs which in turn control rapid bacterial virulence gene expression as well as mecR, which regulates the expression of ß-lactam resistance conferring mecA gene, were both found to be highly upexpressed. EMRSA-15 biofilms, however, were not found to be MecR- or Hfq-dependent, but instead showed upexpression of multiple prophages. This fundamental project aims to dissect the role of mecR, Hfq, and prophages in mediating biofilm formation in USA300 and EMRSA-15. Identifying genes regulated by these key determinants could be better alternatives for biofilm disruption or additive therapies to antibiotics that are currently ineffective against MRSA.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman
• Fellow: De Backer Sarah

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Selection and transmission are key determinants for the dissemination of antimicrobial resistance (AMR) across the planet. These determinants of AMR are frequently studied in laboratory settings while in reality they occur in complex systems, e.g. in microbial communities that colonize human and animal guts or in environmental ecosystems. The central aim of STARCS (Selection and Transmission of Antimicrobial Resistance in Complex Systems) is to characterize and quantify the processes of selection and transmission of AMR genes and drug-resistant bacteria in complex (eco)systems from a 'One Health' perspective and to integrate these elements into predictive mathematical models, which will be used to inform policy development. To reach this goal, the consortium will (i) develop and implement innovative metagenomic methodologies to map the expression of AMR genes and their linkage to bacterial hosts and mobile genetic elements in human, animal and environmental samples, (ii) use relevant animal models (using mice and ducks) and observational studies (in hospitals and in dogs and their owners) to analyse and quantify the processes of selection and transmission of drug-resistant Enterobacteriaceae (specifically Extended Spectrum Beta-Lactamase producing Escherichia coli) and (iii) implement state-of-the-art epidemiological modelling to quantify the spread of ESBL-producing E. coli between humans and animals. STARCS will develop technological breakthroughs to assess selection and transmission dynamics on the level of the resistance gene, the mobile genetic element, the bacterium, the human-animalenvironment interface and in clinical settings. This project will deliver important knowledge into selection and transmission of AMR, will provide the scientific community with novel tools to study selection and transfer of AMR in complex systems and will result in much-needed guidance towards policy decisions by international and national institutions. Ultimately the results from STARCS will form an evidence-based foundation for the development of new regulations, aimed at curbing the spread of AMR.

Researcher(s)

• Promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

General use of vaccines against Streptococcus pneumoniae (S. pneumoniae) in infants has led to a decrease in the presence of the serotypes against which the vaccine was developed. It is a pathogen of which more than 90 different serotypes exist, of whom 10 to 13 are covered by the current vaccines. In order to gain a clear understanding of the S. pneumoniae serotypes carried by infants, and the impact of the vaccine used in the vaccination program, the current study was set up. As early as the first months of our lives S. pneumoniae is present in the nasal cavity and in the pharynx, mostly only temporary and innocuous, yet in some cases, in infants it may lead to infections such as otitis, pneumonia or meningitis. Since the presence of S. pneumoniae is more abundant in some circumstances, the current study focuses on infants between the age of 6 and 30 months either healthy and residing in day-care centres or suffering from an acute middle ear infection. Over a 4 year period, a swab will be taken from the nasal cavity of these infants (700 in first year, 900 in subsequent years, 6800 in total) to investigate presence, density and type of S. pneumoniae carriage, if any, as well as its resistance against antibiotics. The presence of some other pathogens that can cause airway or ear infections will be investigated too. The findings of this study will be extremely valuable to guide decisions on vaccine development, vaccine program, and recommendations on antibiotic treatment.

Researcher(s)

• Promoter: Van Damme Pierre
• Co-promoter: Malhotra Surbhi
• Co-promoter: Theeten Heidi
• Fellow: Wouters Ine

Research team(s)

Project type(s)

• Research Project

Abstract

The general objective of this research group is to gain a better understanding of the formation process and structural characteristics of bacterial and fungal biofilms in humans to ensure future effective therapeutic interventions.

Researcher(s)

• Promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Since two decades, methicillin-resistant Staphylococcus aureus (MRSA) are major causes of medical device-associated and postsurgical wound infections in hospitals and of pneumonia in the community. Recent research shows that in these infections, MRSA favour the biofilm phenotype, living in a community encased in an extracellular matrix that affords protection against the host immune system and antibiotics, making these infections recalcitrant to treatment. Recent data from our laboratory shows that the two most highly pathogenic and globally successful MRSA clones, USA300 and EMRSA-15, are also prolific biofilm formers. Interestingly, transcriptomics has revealed spectacularly different mechanisms of biofilm formation between the two clones. This fundamental project thus aims to dissect the role of novel regulators in mediating biofilm formation in USA300 and EMRSA-15. Identifying genes regulated by these key determinants would initialize identification of targets for biofilm disruption that might be better alternatives to antibiotics that are currently ineffective against MRSA.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

Global (mis)use of antibiotics has led to an alarming emergence and spread of antibiotic resistant bacteria (ARB). Countries like Vietnam with unrestricted, over-the-counter antibiotic use are especially prone to the emergence of pan-resistant 'superbugs' and alarmingly, very few treatment options for life-threatening infections. A burgeoning population and inadequate sanitation facilities have likely exacerbated the ARB reservoir in the Vietnamese environment. This study, carried out in Hanoi city and its surroundings, aims to obtain a longitudinal and holistic view of ARB in the community and hospital environments to identify the ARB selection hotspots in Vietnam. To achieve this, we will determine and finely dissect the ARB burden in various ecosystems (water, food, soil) and in the human gut, and link to the burden of ARB in nosocomial and community-related infections. Also, fitness costs of resistance and the impact of residual antibiotics in the maintenance of ARB in reservoirs and in patients will be elucidated. We will utilize state-of-the-art techniques to characterize ARB and beyond state-of-the-art functional metagenomics to elucidate the resistant metamobilome existing in Vietnamese ecosystems. This transnational study between IEHSD, Vietnam and UA, Belgium will not only facilitate extensive exchange of knowledge and expertise between partners but the results generated here will help to target intervention strategies to tackle this public health crisis.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

Since two decades, methicillin-resistant Staphylococcus aureus (MRSA) has become a major cause of medical device-associated and postsurgical wound infections in hospitals and of pneumonia in the community. In these infections, MRSA favors the biofilm phenotype, living in a community encased in an extracellular matrix that affords protection against the host immune system and antibiotics, making these infections recalcitrant to treatment. Our laboratory has shown that two highly pathogenic and globally successful MRSA clones, USA300 and EMRSA-15, are prolific biofilm formers. Interestingly, our transcriptomics data has revealed spectacularly different mechanisms of biofilm formation between these two clones. For instance, in USA300-S391 biofilms, Hfq, a global regulator of small non-coding RNAs which in turn control rapid bacterial virulence gene expression as well as mecR, which regulates the expression of ß-lactam resistance conferring mecA gene, were both found to be highly upexpressed. EMRSA-15 biofilms, however, were not found to be MecR- or Hfq-dependent, but instead showed upexpression of multiple prophages. This fundamental project aims to dissect the role of mecR, Hfq, and prophages in mediating biofilm formation in USA300 and EMRSA-15. Identifying genes regulated by these key determinants could be better alternatives for biofilm disruption or additive therapies to antibiotics that are currently ineffective against MRSA.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman
• Fellow: De Backer Sarah

Research team(s)

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: Malhotra Surbhi
• Co-promoter: Goossens Herman

Research team(s)

• Laboratory of Medical Microbiology (LMM)

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: Goossens Herman
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

COMPARE aims to harness the rapid advances in molecular technology to improve identification and mitigation of emerging infectious diseases and foodborne outbreaks. To this purpose COMPARE will establish a "One serves all" analytical framework and data exchange platform that will allow real time analysis and interpretation of sequencebased pathogen data in combination with associated data (e.g. clinical, epidemiological data) in an integrated inter-sectorial, interdisciplinary, international, "one health" approach.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

This project addresses the alarming rise of multiple resistant organisms in an holistic approach by analysing simultaneously different reservoirs of antibiotic resistant bacteria (ARB). These findings will be correlated to the presence of ARB in humans (healthy & patients).

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

Incidence of infections caused by multi- and pan-drug resistant Enterobacteriaceae, such as Escherichia coli and Klebsiella, is increasing worldwide. Consequently, colistin, an old and out-of-use antibiotic, had to be re-introduced into clinical practice as a last resort therapeutic option as it is the only antibiotic to which such bacteria still remain susceptible. However, increasing use has inevitably led to emergence of colistin resistance (CR) among Gram-negative bacteria. The main goal of this project is to examine key elements of colistin resistant Enterobacteriaceae (CRE) that have hitherto not been fully investigated. We have established a unique collection of CR E. coli and Klebsiella spp., originating from hospitalized patients and sick animals as well as generated in vivo in a Galleria mellonella moth model, that will form the basis of this project. With these isolates and their colistin sensitive counterparts, we plan to undertake the following: 1, Strain typing; 2, Selection of CR in-vitro; 3, Genome sequencing and comparative genome analysis; 4, Targeted gene sequencing and protein expression; 5, Stability studies; 6, Fitness studies and 7, Assessment of mortality and pathogenicity. While strain typing has been done on few Klebsiella, we will type other CRE to examine if CR is associated with certain strain types. Continuous culture experiments in a morbidostat set-up will allow in vitro selection of CRE under continuous drug pressure that will be studied temporally at various stages of resistance development. Whole genome sequencing of in-vivo and in-vitro CRE isogenic strains will identify the sites of mutations potentially responsible for CR. Gene targets identified by genome analysis will be re-sequenced to confirm the changes conferring CR and those will be further characterized by real-time PCR and proteomics. The stability of CR and fitness of such strains will be assessed either by passaging in colistin-free medium, or under constant colistin pressure on the morbidostat model. The effects of CR on mortality will be investigated in the high-throughput reproducible in vivo Galleria mellonella model. Finally, the impact of CR on virulence and pathogenicity will be studied in a higher animal model i.e., a ventilator-associated pneumonia rat model that is already established in our laboratory.

Researcher(s)

• Promoter: Malhotra Surbhi
• Co-promoter: Goossens Herman
• Co-promoter: Sabirova Julia
• Fellow: Xavier Basil Britto

Research team(s)

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

In ROUTINE, 3 SMEs and 2 Universities will develop a prototype benchtop instrument that will rapidly (< 30 min) detect bacteria and characterize key antibiotics resistance profiles of ESBL (extended spectrum betalactamase) and carbapenemase producing GNB directly from the patient urine at the point of care in outpatients and hospitals at a low cost (~20 €/test) and with near 100% sensitivity and specificity.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

Our study proposes to firstly identify early predictors of pneumonia and secondly, utilize both human samples and rodent models to investigate distinct host-pathogen signatures during colonization and development of VAP by two marker organisms, Pseudomonas aeruginosa and Escherichia coli that not only show diverse pathogenetic profiles but are also most important for VAP etiology.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

In this project, we aim to: (1) Investigate gene expression profiles of planktonic cultures and of MRSA biofilms developed in vitro and, (2) Validate the identified 'biofilm markers' on patient samples (blood, wound swabs and sputum).

Researcher(s)

• Promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

The research of Surbhi Malhotra has focused on the molecular epidemiology and genetics of resistance to antimicrobials in oral streptococci. Applying molecular biological techniques on oro-pharyngeal streptococcal flora in healthy individuals as a model, she demonstrated that antibiotic use is the single most important driver of antibiotic-resistance in vivo, that antibiotics belonging to the same class can differ widely in resistance gene selection, and that differences in predominance of certain resistance genes in geographically distinct areas might be linked to the preferential use of specific antibiotic subclasses. Her current research interests include studying the impact of antibiotic use on the naso-oro-pharyngeal and intestinal microflora, mechanisms of biofilm formation, bacterial pathogenetic mechanisms, and developing rapid diagnostic assays for pathogens causing community-acquired and nosocomial infections.

Researcher(s)

• Promoter: Malhotra Surbhi
• Fellow: Malhotra Surbhi

Research team(s)

• Laboratory of Medical Microbiology (LMM)

Project type(s)

• Research Project

Abstract

R-GNOSIS (2011-2015) combines 5 international clinical intervention studies, all supported by highly innovative microbiology and mathematical modelling, to determine - in the most relevant patient populations - the efficacy and effectiveness of cutting-edge interventions to reduce acquisition, carriage, infection and spread of Multi-Drug Resistant Gram-negative Bacteria (MDR-GNB). All clinical work-packages (WPs) will progress science beyond the state-of-the-art in generating new and translational clinically relevant knowledge, through hypothesis-driven studies with a focus on patient-centred outcomes that matter to the people of Europe and beyond. The studies and analyses proposed in R-GNOSIS will generate a step-change in identifying evidence-based preventive measures and clinical guidance for primary care and hospital-based physicians, as well as health-care authorities, to combat the spread and impact of the unprecedented rise of infections caused by MDR-GNB in Europe. The University of Antwerp (UA) is leading the work package on 'Functional microbiology and within-host transmission dynamics of genes, plasmids and clones of MDR-GNB'. Here, we will apply a "bedside-to-bench" translational approach to study the impact of antibiotics and gut decolonization on MDR-GNB pathogens and commensals in the community or hospital utilizing state-of-the-art microbiological tools. Our sophisticated in vitro analyses to investigate resistance gene transfer and the ecology and evolution of resistance will also facilitate ground-breaking modelling studies. Results from the diagnostic interventions planned here will revolutionize current screening practices for MDR-GNBs in hospitals and introduce the use of point-of-care testes (POCTs) in primary care.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

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

The present study aims to combine culture-independent high-resolution sequencing techniques with functional screens to fully characterize the human naso-oro-pharyngeal microbiome and study variations in the antibiotic resistance reservoir in geographically diverse European populations.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

The main aim of this study is to provide a comprehensive picture of the level of clinical relevant antibiotic resistant bacteria (ARB) in the environment and commensal flora in Gauteng/South Africa. Besides, the genetic relatedness of these ARB will be studied to understand the mechanisms of antibiotic resistance dissemination in the community.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Colebunders Robert
• Co-promoter: Malhotra Surbhi
• Fellow: Paasch Fabienne

Research team(s)

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

SATURN (Impact of Specific Antibiotic Therapies on the prevalence of hUman host ResistaNt bacteria; 2010-2014) is a collaborative research project that is funded as part of the 7th framework programme by the EU. SATURN aims to improve methodological standards and conduct research that will help to better understand the impact of antibiotic use on acquisition, selection and transmission of antimicrobial resistance (AMR) in different environments, by combining analyses of molecular, individual patient-level as well as ecologic data. The anticipated results may guide clinical and policy decisions to ultimately reduce the burden of AMR in Europe. Several clinical trials conducted both in hospitals and in the community will serve as a platform for basic microbiological and pharmacological research carried out by several academic institutions throughout Europe. The University of Antwerp (UA) is coordinating the work package on bacterial genetics and functional studies. The main objective of this WP is to study the abilities of various antibiotics to select for resistance in the respiratory and intestinal flora of patients and their contacts or in nonantibiotic-treated controls and compare the persistence of the selected resistant bacteria over time following antibiotic administration. The functional and genetic studies planned here will utilize both in vitro and in vivo models to dissect the human microbiome. Further studies on the population biology, clonal fitness, and virulence potential of antibiotic-resistant and antibiotic-sensitive bacteria will uncover the mechanisms underlying the successful dissemination of major AMR clones in Europe.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

A first objective of the project is the identification of genes encoding novel virulence factors, which are expressed at the bacterial surface of MRSA. A second objective is to study the differences in biofilm-forming capabilities between hospital-acquired (HA) and community-acquired (CA)-MRSA in the presence and absence of antibiotic pressure. A third objective of this project is to find an explanation why certain MRSA clones are highly epidemic.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

This is a fundamental research project financed by the Research Foundation - Flanders (FWO). The project was subsidized after selection by the FWO-expert panel.

Researcher(s)

• Promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

InTopSens aims to design fast photonic label-free smart biosensors with detection limits below 1 pg/mm2, and integrate multiple biosensors on a disposable label-free photonic biochip capable of identifying and determining antibiotic resistance of bacteria causing sepsis. Severe sepsis or septic shock is characterized by multi-organ dysfunction, failure and finally death. In the EU, sepsis is estimated to cause a loss of up to 146,000 lives every year and up to EUR 7.6 billion in patient health care costs. The most important intervention is rapid diagnosis followed by appropriate antibiotic treatment. However, the currently available 'rapid' assays are laboratory based with a total assay time of up to 12 hours, e.g. PCR. Hence, more often than not, antibiotic treatment has to be instituted empirically before test results arrive and this non-targeted, and quite often inappropriate, antibiotic use has led to multidrug resistance amongst bacteria including those causing sepsis. We intend to develop the InTopSens device into a modular assay for sepsis to detect the causative pathogen and also profile its antibiotic resistance at the patient's bed-side in Emergency/Intensive Care Units in hospitals. Upon introduction of a large drop of blood (~ 50 µl) onto the chip, presence of bacteria and identification to the genus/species level will be obtained within 5-10 mins, while the antibiotic resistance profile of the bacterial pathogen will be available within 30 mins. Some 120 sensing areas/datapoints are needed to identify this profile and as such due to the very high integration up to 5 assays can be integrated onto a 1cm2 chip of the same bacteria for higher sensitivity and selectivity or for other bacteria. A final prototype consisting of a packaged biochip will be validated both preclinically and clinically to assess the potential of this sepsis assay in preventing/reducing inappropriate antibiotic therapy and mortality in sepsis patients.

Researcher(s)

• Promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

Telithromycin (Tel), an advanced macrolide was developed to combat macrolide-resistant pathogens, although some S. pyogenes harbouring the erm(B) methylase can exhibit Tel resistance (Tel-R). However, we have evidenced, for the first time, Tel efflux mediated by a reserpine-sensitive pump in high-level Tel-R S. pyogenes that also harbour erm(B). Gene expression studies are planned to unequivocally establish the contribution of this pump to Tel-R.

Researcher(s)

• Promoter: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of this project is 1. Analyse baseline resistance and changes effected by amoxicillin use on the oropharyngeal bacteria of LRTI patients and study the mechanisms of phenotypic tolerance in this patient population. 2. Elucidate telithromycin resistance mechanisms in SPY. 3. Determine the fitness costs and any compensatory mutations in macrolide- (including telithromycin) resistant SPY and amoxicillin-resistant SPN.

Researcher(s)

• Promoter: Goossens Herman
• Fellow: Malhotra Surbhi

Research team(s)

Project type(s)

• Research Project