P118

1:CNC - Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3004-504 Coimbra, Portugal; 2:CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, 3004-504 Coimbra, Portugal; 3:Department of Life Sciences, University of Coimbra, Coimbra, 3000-456 Coimbra, Portugal; 4:TimeUp Lda, IPN incubator, Coimbra, 3030-199 Coimbra, Portugal

Nontuberculous mycobacteria (NTM) are opportunistic pathogens of growing public health concern, owing to their intrinsic antibiotic resistance and persistence in human-engineered environments. This study explores microbial interactions involving NTM from both environmental and clinical origins, aiming to uncover competitive relationships and identify potential sources of antimycobacterial compounds. We investigated interactions between NTM and methylobacteria, co-inhabitants of drinking water systems, as well as with skin-associated bacteria. Co-culture and mixed biofilm assays demonstrated that several methylobacterial and skin-derived isolates effectively inhibited the growth and biofilm formation of both environmental and clinical NTM strains. Clinical NTM isolates showed markedly higher antibiotic resistance and biofilm-forming capacity, aligning with their enhanced pathogenic potential. Whole-genome sequencing of active isolates revealed biosynthetic gene clusters (BGCs) potentially encoding diverse secondary metabolites, including candidates related to known antimycobacterial agents. Overall, antimicrobial activity was attributed to diffusible molecules, with some strains requiring competitive conditions to trigger bioactivity. These findings highlight the dynamic competitive ecology of NTM in both environmental and host-associated niches and emphasize the potential of microbial interactions and/or antagonism as a source of novel antimycobacterials. By integrating perspectives from waterborne and skin-associated microbiota, this work advances our understanding of NTM ecology and pathogenesis and suggests new strategies for targeted control of NTM infections.

Funding: PTDC/BIA-MIC/0122/2021, 2022.06809.PTDC, UIDB/04539/2020, UIDP/04539/2020, LA/P/0058/2020, DL57/2016-SFRH/BPD/108299/2015.