TY - JOUR
T1 - Global phylogenomic analyses of Mycobacterium abscessus provide context for non cystic fibrosis infections and the evolution of antibiotic resistance
AU - Bronson, Ryan A.
AU - Gupta, Chhavi
AU - Manson, Abigail L.
AU - Nguyen, Jan A.
AU - Bahadirli-Talbott, Asli
AU - Parrish, Nicole M.
AU - Earl, Ashlee M.
AU - Cohen, Keira A.
N1 - Funding Information:
This project was funded with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Grant Number U19AI110818 to the Broad Institute, and the National Heart, Lung and Blood Institute under K08HL139994 to K.A.C. Additional funding for K.A.C. includes support from the Burroughs Wellcome Fund Career Award for Medical Scientists. We would like to thank Josephine Bryant and Andres Floto for guidance on the use of their data. We would also like to thank Rauf Salamzade, Lucas Van Dijk, Tim Straub, Colin Worby, and other members of the Broad Bacterial Genomics Group for helpful discussions.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Mycobacterium abscessus (MAB) is an emerging pathogen that leads to chronic lung infections. To date, the global population structure of non-cystic fibrosis (CF) MAB and evolutionary patterns of drug resistance emergence have not been investigated. Here we construct a global dataset of 1,279 MAB whole genomes from CF or non-CF patients. We utilize whole genome analysis to assess relatedness, phylogeography, and drug resistance evolution. MAB isolates from CF and non-CF hosts are interspersed throughout the phylogeny, such that the majority of dominant circulating clones include isolates from both populations, indicating that global spread of MAB clones is not sequestered to CF contexts. We identify a large clade of M. abscessus harboring the erm(41) T28C mutation, predicted to confer macrolide susceptibility in this otherwise macrolide-resistant species. Identification of multiple evolutionary events within this clade, consistent with regain of wild type, intrinsic macrolide resistance, underscores the critical importance of macrolides in MAB.
AB - Mycobacterium abscessus (MAB) is an emerging pathogen that leads to chronic lung infections. To date, the global population structure of non-cystic fibrosis (CF) MAB and evolutionary patterns of drug resistance emergence have not been investigated. Here we construct a global dataset of 1,279 MAB whole genomes from CF or non-CF patients. We utilize whole genome analysis to assess relatedness, phylogeography, and drug resistance evolution. MAB isolates from CF and non-CF hosts are interspersed throughout the phylogeny, such that the majority of dominant circulating clones include isolates from both populations, indicating that global spread of MAB clones is not sequestered to CF contexts. We identify a large clade of M. abscessus harboring the erm(41) T28C mutation, predicted to confer macrolide susceptibility in this otherwise macrolide-resistant species. Identification of multiple evolutionary events within this clade, consistent with regain of wild type, intrinsic macrolide resistance, underscores the critical importance of macrolides in MAB.
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U2 - 10.1038/s41467-021-25484-9
DO - 10.1038/s41467-021-25484-9
M3 - Article
C2 - 34446725
AN - SCOPUS:85113601100
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5145
ER -