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

Details

• Personal Author:
  Bailey TC ; Brunham C-AD ; Caverly LJ ; Choi J ; Dantas G ; Fishbein S ; Keen EC ; Mehta SB ; Mejia-Chew CR ; Prusa J ; Wallace MA ; Zimbric M
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Cohort Studies Environmental Exposure Genetics Lung Diseases Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Antimicrobial Resistance Author Keywords: Mycobacterium Abscessus Complex Bacterial Infections Cohort Studies Comparative Genomics Environmental Exposure Genes Genomics In-host Adaptation Longitudinal Study Lung Disease Mycobacterium Nontuberculous Mycobacteria Pathogens

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• ISSN:
  0022-1899
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Michigan ; Missouri ; OSHA Region 5 ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  321-331
• Volume:
  228
• Issue:
  3
• NIOSHTIC Number:
  nn:20068225
• Citation:
  J Infect Dis 2023 Aug; 228(3):321-331
• Contact Point Address:
  Carey-Ann D. Burnham, PhD, Washington University in St. Louis, School of Medicine, 660. S Euclid Ave., St. Louis, MO 63110
• Email:
  cburnham@wustl.edu
• Federal Fiscal Year:
  2023
• Performing Organization:
  Washington University, Saint Louis
• Peer Reviewed:
  True
• Start Date:
  20180901
• Source Full Name:
  The Journal of Infectious Diseases
• End Date:
  20220831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:be85ef7ea6e261e6f7d3aa90515e6b207e398bcab32a3a01e3c2e6b0830d9fba6295b4420394da17e9b0c74faac861ca41ce75d0fb5e6269dee8c9d42d44124c
• Download URL:
  https://stacks.cdc.gov/view/cdc/230428/cdc_230428_DS1.pdf
• File Type:
  [PDF - 2.80 MB ]