OR18

1:Institut d'investigació en Ciències de la Salut Germans Trias i Pujol; 2:Instituto de Investigación Sanitaria Gregorio Marañón; 3:Hospital Universitari Germans Trias i Pujol

Mycobacterium abscessus is a rapidly growing non-tuberculous mycobacterium associated with chronic pulmonary infections known for its intrinsic antibiotic resistance. With its rising clinical relevance, there is an increasing need for in vivo models that enable rapid and scalable assessment of virulence and host–pathogen interactions. In this study, we employed Drosophila melanogaster as a genetically tractable model to investigate the pathogenicity of different M. abscessus clinical isolates. The selected isolates represent five distinct genotypes collected over a 16-year period from a single patient with a persistent infection, offering a unique perspective on within-host bacterial evolution. Notably, all but one of the genotypes harboured mutations potentially associated with hypermutation, providing an opportunity to explore how genomic changes influence virulence. Adult flies were systemically infected, with survival rates and immune responses monitored over time, and bacterial loads measured at the time of death. Our results revealed distinct virulence strategies among variants: some caused rapid mortality but required higher bacterial loads, while others induced delayed mortality at significantly lower bacterial burdens. These findings suggest that M. abscessus may employ diverse mechanisms to subvert host defences and establish infection. This model not only captures key aspects of infection dynamics observed in more complex organisms but also provides a rapid, cost-effective and ethical platform for preclinical screening of virulence factors and potential therapeutics. Overall, the use of D. melanogaster as an in vivo model offers valuable insights into M. abscessus pathogenesis and within-host evolution.