Genomics of Non-Tuberculosis Mycobacteria

Non-tuberculous mycobacteria (NTM) are a ubiquitous group of diverse environmental mycobacteria related to Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). A significant number of NTMs can also cause clinical disease, although many are non-pathogenic. Diseases caused by NTM infections are important sources of morbidity and mortality throughout the world, with a resurgence of infections in the United States. NTMs, once considered low risk to humans, are now recognized as major opportunistic pathogens, especially in immunocompromised individuals. NTM infection is recognized to play a role in the exacerbation of chronic pulmonary disorders. Over 150 Mycobacterium species have been validly published to date, according to the List of Prokaryotic Names with Standing in Nomenclature (LPSN) (http://www.bacterio.net/mycobacterium.html) and elsewhere (http://www.dsmz.de/bacterial-diversity/prokaryotic-nomenclature-up-to-date).  The most common NTMs capable of causing disease include  M. avium (or M. avium complex - MAC), M. kansasii, and M. fortuitum; less common NTMs include M. intracellulare, M. abscessus, M. szulgae, M. chelonae, M. terrae, M. gordanae, M. xenopi, and M. simiae; three predominantly skin isolates of NTM are M. leprae, M. ulcerans, and M. marinum.

While M. tuberculosis complex strains responsible for tuberculosis have been the subject of much investigation (including M. tuberculosis, M. bovis, M. africanum, M. canettii, M. microti, M. caprae, and M. pinnipedii), the host-pathogen interactions of NTMs remain poorly characterized. Importantly, the background prevalence of NTMs has been shown to interfere with important aspects of TB disease control and management, including the efficacy of new TB vaccines, established immuno-diagnostic methods, and the specificity of diagnostic and immune biomarkers. While the impact of NTMs on TB disease control and management is recognized, the mechanistic actions of NTMs need to be elucidated. Data on NTM prevalence in TB-endemic countries, however, is limited and often under-reported. Possible factors contributing to under-reporting include overlapping clinical manifestations of TB and NTM disease, lack of awareness of NTMs, and insufficient laboratory infrastructure to identify and culture NTMs.

We undertook to sequence, analyze and characterize NTM strains representing geographically diverse TB-endemic areas with high NTM prevalence. Ancillary findings from adolescent and neonatal cohort studies conducted by Aeras to determine the incidence and prevalence of TB in Cambodia, India, Mozambique, South Africa, and Uganda included the prevalence and typing of NTM infections. The sites that participated in these studies collected NTM samples which were sequenced by JCVI.

Funding