Repository logo
 

Stepwise pathogenic evolution of Mycobacterium abscessus.

Accepted version
Peer-reviewed

Type

Article

Change log

Abstract

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.

Description

Keywords

Communicable Diseases, Emerging, Datasets as Topic, Epigenesis, Genetic, Evolution, Molecular, Gene Transfer, Horizontal, Genetic Fitness, Genome, Bacterial, Humans, Lung, Mutation, Mycobacterium Infections, Nontuberculous, Mycobacterium abscessus, Pneumonia, Bacterial, Virulence

Journal Title

Science

Conference Name

Journal ISSN

0036-8075
1095-9203

Volume Title

372

Publisher

American Association for the Advancement of Science (AAAS)

Rights

All rights reserved
Sponsorship
Wellcome Trust (110224/Z/15/Z)
Cystic Fibrosis Trust (IH 001)
Wellcome Trust (107032/B/15/Z)
Wellcome Trust (107032/Z/15/Z)