Genomic Analyses of Longitudinal Mycobacterium abscessus Isolates in a Multicenter Cohort Reveal Parallel Signatures of In-Host Adaptation.

Autor:	Choi J; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine in St Louis, St Louis, Missouri, USA., Keen EC; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine in St Louis, St Louis, Missouri, USA., Wallace MA; Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA., Fishbein S; Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA., Prusa J; Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA., Zimbric M; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA., Mejia-Chew CR; Department of Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA., Mehta SB; Department of Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA., Bailey TC; Department of Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA., Caverly LJ; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA., Burnham CD; Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.; Department of Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.; Department of Pediatrics, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.; Department of Molecular Microbiology, Washington University School of Medicine in St Louis, St Louis, Missouri, USA., Dantas G; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.; Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.; Department of Pediatrics, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.; Department of Molecular Microbiology, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.; Department of Biomedical Engineering, Washington University in St Louis, St Louis, Missouri, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2023 Aug 11; Vol. 228 (3), pp. 321-331.
DOI:	10.1093/infdis/jiad187
Abstrakt:	Background: Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an increasingly frequent cause of opportunistic infections. Mycobacterium abscessus complex (MABC) is one of the major NTM lung pathogens that disproportionately colonize and infect the lungs of individuals with cystic fibrosis (CF). MABC infection can persist for years, and antimicrobial treatment is frequently ineffective. Methods: We sequenced the genomes of 175 isolates longitudinally collected from 30 patients with MABC lung infection. We contextualized our cohort amidst the broader MABC phylogeny and investigated genes undergoing parallel adaptation across patients. Finally, we tested the phenotypic consequences of parallel mutations by conducting antimicrobial resistance and mercury-resistance assays. Results: We identified highly related isolate pairs across hospital centers with low likelihood of transmission. We further annotated nonrandom parallel mutations in 22 genes and demonstrated altered macrolide susceptibility co-occurring with a nonsynonymous whiB1 mutation. Finally, we highlighted a 23-kb mercury-resistance plasmid whose loss during chronic infection conferred phenotypic susceptibility to organic and nonorganic mercury compounds. Conclusions: We characterized parallel genomic processes through which MABC is adapting to promote survival within the host. The within-lineage polymorphisms we observed have phenotypic effects, potentially benefiting fitness in the host at the putative detriment of environmental survival. Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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