Mycobacterium chelonae as an Underrecognized Cause of Granulomatous Disease in Fish and Humans: A Molecular One Health Study

Non-tuberculous mycobacteria are recognized as pathogens affecting aquatic animals and
humans. Although Mycobacterium marinum is traditionally considered the principal etiolog￾ical agent of fish mycobacteriosis and fish-tank granuloma in humans, the contribution of
Mycobacterium chelonae in fish as well as in humans remains underestimated, particularly in
Ziehl–Neelsen (ZN)-negative lesions. In this study, granulomatous lesions of marine fish
species and human skin biopsies were investigated using histopathology and molecular
diagnostics. Following histological evaluation, all samples were analysed by PCR amplifi￾cation and sequencing of the hsp65 gene to identify the causative agent. Fish and human
tissues showed similar chronic granulomatous lesions, with all cases negative for acid-fast
bacilli by ZN staining. Molecular analysis consistently identified M. chelonae in both marine
fish organs and human skin lesions exhibiting clinicopathological features traditionally
attributed to M. marinum. Phylogenetic analysis revealed high genetic similarity between
fish- and human-derived sequences, suggesting shared environmental reservoirs rather
than host-specific lineages. These findings identify M. chelonae as an underrecognized
cause of granulomatous disease in fish and humans and demonstrate the limitations of
histochemical methods in these infections. Incorporating molecular diagnostics into routine
investigations of granulomatous disease supports more accurate diagnosis across veterinary
and human medicine and strengthens One Health surveillance of aquatic non-tuberculous
mycobacterial infections.