Mycobacterium avium complex MAC contains clinically important non-tuberculous mycobacteria worldwide and is the second largest medical complex in the Mycobacterium genus after the Mycobacterium tuberculosis complex. MAC is comprised of several species, which are very close phylogenetically related, but they are very diverse regarding their host preference, course of disease, virulence and immune response. In this study, we provide immunological and virulence-related insights into the M. colombiense genome as a model of an opportunistic pathogen in the MAC. By using bioinformatic tools we found that M. colombiense has deletions in the genes involved in the p-HBA/PDIM/PGL, PLC, SL-1 and HspX production, and loss of the ESX-1 locus. This information not only gives us light for understanding the virulence mechanisms employed by opportunistic MAC pathogens, but also it has great potential for the designing of species-specific diagnostic tools.