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.
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