Genomic insights and functional adaptation of Mycobacterium intracellulare strains isolated from patients with inflammatory bowel disease.

In clinical practice, inappropriate diagnosis of inflammatory bowel disease (IBD) ascribing the disease to Mycobacterium avium paratuberculosis (MAP) and resulting mistreatment has been a challenge for healthcare workers. This highlights the need to accurately identify and characterize MAP members in patients with gastrointestinal (GI) ulceration. A total of 889 patients exhibiting symptoms of IBD were examined for MAP infection. While MAP was not recovered from any of the specimens, we successfully isolated and sequenced four clinically relevant Mycobacterium intracellulare genomes from GI samples of patients diagnosed with IBD. In-depth phylogenomic and comparative genomics demonstrated genomic heterogeneity and variable metabolic profile in M. intracellulare species. Analysis of four isolate genomes disclosed an ongoing genome reduction process, which might be crucial for adaptation and increased virulence of intestinal M. intracellulare strains. Findings provide insights into the narrow-spectrum resistance to antibiotics, metabolic adaptation, and potential virulence of M. intracellulare strains, particularly those associated with human infections. Recombination analysis revealed minimal recombination and higher mutational divergence, which indicate evolutionary constraints leading to clonal evolution of M. intracellulare species.

Importance: The present study provides valuable insights on genomic diversity, metabolic adaptability, and virulence of Mycobacterium intracellulare strains infecting human host. Our findings highlight the need for additional research on essential genes as potential drug targets. An updated knowledge on intestinal M. intracellulare strains regarding its genomic characteristics and evolutionary processes is critical to design better diagnostic and treatment approaches for intestinal infections.