Stepwise pathogenic evolution of Mycobacterium abscessus

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works..

Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as Mycobacterium tuberculosis, have evolved to cause transmissible human infection. By analyzing the recent emergence and spread of the environmental organism M. abscessus through the global cystic fibrosis population, we have defined key, generalizable steps involved in the pathogenic evolution of mycobacteria. We show that epigenetic modifiers, acquired through horizontal gene transfer, cause saltational increases in the pathogenic potential of specific environmental clones. Allopatric parallel evolution during chronic lung infection then promotes rapid increases in virulence through mutations in a discrete gene network; these mutations enhance growth within macrophages but impair fomite survival. As a consequence, we observe constrained pathogenic evolution while person-to-person transmission remains indirect, but postulate accelerated pathogenic adaptation once direct transmission is possible, as observed for M. tuberculosis Our findings indicate how key interventions, such as early treatment and cross-infection control, might restrict the spread of existing mycobacterial pathogens and prevent new, emergent ones.

Errataetall:

CommentIn: Science. 2021 Apr 30;372(6541):465-466. - PMID 33926941

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:372

Enthalten in:

Science (New York, N.Y.) - 372(2021), 6541 vom: 30. Apr.

Sprache:

Englisch

Beteiligte Personen:

Bryant, Josephine M [VerfasserIn]
Brown, Karen P [VerfasserIn]
Burbaud, Sophie [VerfasserIn]
Everall, Isobel [VerfasserIn]
Belardinelli, Juan M [VerfasserIn]
Rodriguez-Rincon, Daniela [VerfasserIn]
Grogono, Dorothy M [VerfasserIn]
Peterson, Chelsea M [VerfasserIn]
Verma, Deepshikha [VerfasserIn]
Evans, Ieuan E [VerfasserIn]
Ruis, Christopher [VerfasserIn]
Weimann, Aaron [VerfasserIn]
Arora, Divya [VerfasserIn]
Malhotra, Sony [VerfasserIn]
Bannerman, Bridget [VerfasserIn]
Passemar, Charlotte [VerfasserIn]
Templeton, Kerra [VerfasserIn]
MacGregor, Gordon [VerfasserIn]
Jiwa, Kasim [VerfasserIn]
Fisher, Andrew J [VerfasserIn]
Blundell, Tom L [VerfasserIn]
Ordway, Diane J [VerfasserIn]
Jackson, Mary [VerfasserIn]
Parkhill, Julian [VerfasserIn]
Floto, R Andres [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 13.05.2021

Date Revised 31.10.2021

published: Print

CommentIn: Science. 2021 Apr 30;372(6541):465-466. - PMID 33926941

Citation Status MEDLINE

doi:

10.1126/science.abb8699

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM324801661