TY - JOUR
T1 - Comparative genomics of mycobacterium avium complex reveals signatures of environment-specific adaptation and community acquisition
AU - Keen, Eric C.
AU - Choi, Joo Hee
AU - Wallace, Meghan A.
AU - Azar, Michelle
AU - Mejia-Chew, Carlos R.
AU - Mehta, Shail B.
AU - Bailey, Thomas C.
AU - Caverly, Lindsay J.
AU - Burnham, Carey Ann D.
AU - Dantasa, Gautam
N1 - Funding Information:
This work was supported in part by awards to G.D. from the National Institute for Occupational Safety and Health of the U.S. Centers for Disease Control and Prevention (R01 OH011578) and from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI123394) and to L.J.C. from the Cystic Fibrosis Foundation (CAVERL17A0) and the National Heart, Lung, and Blood Institute of the NIH (K23HL136934). E.C.K. is supported by a Graduate Research Fellowship from the National Science Foundation (DGE-1143945).
Publisher Copyright:
Copyright © 2021 Keen et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution 4.0 International license.
PY - 2021/9
Y1 - 2021/9
N2 - Nontuberculous mycobacteria, including those in the Mycobacterium avium complex (MAC), constitute an increasingly urgent threat to global public health. Ubiquitous in soil and water worldwide, MAC members cause a diverse array of infections in humans and animals that are often multidrug resistant, intractable, and deadly. MAC lung disease is of particular concern and is now more prevalent than tuberculosis in many countries, including the United States. Although the clinical importance of these microorganisms continues to expand, our understanding of their genomic diversity is limited, hampering basic and translational studies alike. Here, we leveraged a unique collection of genomes to characterize MAC population structure, gene content, and within-host strain dynamics in unprecedented detail. We found that different MAC species encode distinct suites of biomedically relevant genes, including antibiotic resistance genes and virulence factors, which may influence their distinct clinical manifestations. We observed that M. avium isolates from different sources-human pulmonary infections, human disseminated infections, animals, and natural environments-are readily distinguished by their core and accessory genomes, by their patterns of horizontal gene transfer, and by numerous specific genes, including virulence factors. We identified highly similar MAC strains from distinct patients within and across two geographically distinct clinical cohorts, providing important insights into the reservoirs which seed community acquisition. We also discovered a novel MAC genomospecies in one of these cohorts. Collectively, our results provide key genomic context for these emerging pathogens and will facilitate future exploration of MAC ecology, evolution, and pathogenesis.
AB - Nontuberculous mycobacteria, including those in the Mycobacterium avium complex (MAC), constitute an increasingly urgent threat to global public health. Ubiquitous in soil and water worldwide, MAC members cause a diverse array of infections in humans and animals that are often multidrug resistant, intractable, and deadly. MAC lung disease is of particular concern and is now more prevalent than tuberculosis in many countries, including the United States. Although the clinical importance of these microorganisms continues to expand, our understanding of their genomic diversity is limited, hampering basic and translational studies alike. Here, we leveraged a unique collection of genomes to characterize MAC population structure, gene content, and within-host strain dynamics in unprecedented detail. We found that different MAC species encode distinct suites of biomedically relevant genes, including antibiotic resistance genes and virulence factors, which may influence their distinct clinical manifestations. We observed that M. avium isolates from different sources-human pulmonary infections, human disseminated infections, animals, and natural environments-are readily distinguished by their core and accessory genomes, by their patterns of horizontal gene transfer, and by numerous specific genes, including virulence factors. We identified highly similar MAC strains from distinct patients within and across two geographically distinct clinical cohorts, providing important insights into the reservoirs which seed community acquisition. We also discovered a novel MAC genomospecies in one of these cohorts. Collectively, our results provide key genomic context for these emerging pathogens and will facilitate future exploration of MAC ecology, evolution, and pathogenesis.
UR - http://www.scopus.com/inward/record.url?scp=85117792009&partnerID=8YFLogxK
U2 - 10.1128/mSystems.01194-21
DO - 10.1128/mSystems.01194-21
M3 - Article
C2 - 34665012
AN - SCOPUS:85117792009
SN - 2379-5077
VL - 6
JO - mSystems
JF - mSystems
IS - 5
M1 - e01194-21
ER -