Stepwise pathogenic evolution of Mycobacterium abscessus

Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as , have evolved to cause transmissible human infection. By analyzing the recent emergence and spread of the environmental organism through the global cystic fibrosis population, we have defined key, gene...

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Bibliographic Details
Published in:	Science (American Association for the Advancement of Science) 2021-04, Vol.372 (6541)
Main Authors:	Bryant, Josephine M, Brown, Karen P, Burbaud, Sophie, Everall, Isobel, Belardinelli, Juan M, Rodriguez-Rincon, Daniela, Grogono, Dorothy M, Peterson, Chelsea M, Verma, Deepshikha, Evans, Ieuan E, Ruis, Christopher, Weimann, Aaron, Arora, Divya, Malhotra, Sony, Bannerman, Bridget, Passemar, Charlotte, Templeton, Kerra, MacGregor, Gordon, Jiwa, Kasim, Fisher, Andrew J, Blundell, Tom L, Ordway, Diane J, Jackson, Mary, Parkhill, Julian, Floto, R Andres
Format:	Article
Language:	eng
Subjects:	Adaptation Bronchopulmonary infection Cell survival Chronic infection Cloning Communicable Diseases, Emerging - microbiology Communicable Diseases, Emerging - transmission Contamination Cross-infection Cystic fibrosis Datasets as Topic Disease control Epigenesis, Genetic Epigenetics Evolution Evolution, Molecular Evolutionary genetics Fitness Fomites Gene transfer Gene Transfer, Horizontal Genes Genetic Fitness Genome, Bacterial Genomic analysis Horizontal transfer Humans Infections Infectivity Inflammation Lung - microbiology Lungs Macrophages Multidrug resistance Mutation Mycobacterium abscessus Mycobacterium abscessus - genetics Mycobacterium abscessus - pathogenicity Mycobacterium Infections, Nontuberculous - microbiology Mycobacterium Infections, Nontuberculous - transmission Mycobacterium tuberculosis Pathogenicity Pathogens Patients Pneumonia, Bacterial - microbiology Pneumonia, Bacterial - transmission Population density Regulators Reproductive fitness Saprophytes Species Survival Transcription Tuberculosis Virulence Virulence - genetics
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Summary:	Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as , have evolved to cause transmissible human infection. By analyzing the recent emergence and spread of the environmental organism 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 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.
ISSN:	0036-8075 1095-9203