P067

1:University of Antwerp; 2:KU Leuven

Among the non-tuberculous mycobacteria (NTM), Mycobacterium abscessus (Mab) raises substantial concern due to its high pathogenicity and pronounced resistance to current treatment options. It is an emerging pathogen primarily responsible for pulmonary and skin infections. With cure rates below  50 %, it is considered the most difficult to treat pathogen of the NTM. Given the chronic nature and high relapse rate of Mab pulmonary disease, there is an increasing interest in understanding the role of persistence in these infections.

Therefore, this study aims to characterize antibiotic-induced persistence in Mab, while also considering other triggers of persistence, such as growth rate, nutrient availability and the lung environment. Firstly, Mab ATCC 19977 was treated with different concentrations of amikacin, clarithromycin, moxifloxacin and rifabutin. Based on biphasic killing and heritability assays, persisters were identified under treatment with 100 times the minimal inhibitory concentration (MIC) of moxifloxacin and rifabutin. Experiments were conducted under nutrient-rich and nutrient-starved conditions with preliminary results indicating that nutrient-starvation increases persister formation. To increase clinical relevance, combinations of different antibiotics are currently being tested. Lastly, given that Mab predominantly causes disease in cystic fibrosis patients, persister formation is studied in artificial sputum medium designed to mimic these lung conditions and future experiments will also include clinical isolates.

This study seeks to contribute to a deeper understanding of the conditions and mechanisms involved in the formation of Mab persistence. This could help clarify why current treatments fail, which could be essential for the identification of new therapeutic targets.