Microevolution, reinfection and highly complex genomic diversity in patients with sequential isolates of Mycobacterium abscessus

Nat Commun. 2024 Mar 28;15(1):2717. doi: 10.1038/s41467-024-46552-w.

Abstract

Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent infections. Our aim was to characterize microevolution/reinfection events in persistent infections. Fifty-three sequential isolates from 14 patients were sequenced to determine SNV-based distances, assign resistance mutations and characterize plasmids. Genomic analysis revealed 12 persistent cases (0-13 differential SNVs), one reinfection (15,956 SNVs) and one very complex case (23 sequential isolates over 192 months), in which a first period of persistence (58 months) involving the same genotype 1 was followed by identification of a genotype 2 (76 SNVs) in 6 additional alternating isolates; additionally, ten transient genotypes (88-243 SNVs) were found. A macrolide resistance mutation was identified from the second isolate. Despite high diversity, the genotypes shared a common phylogenetic ancestor and some coexisted in the same specimens. Genomic analysis is required to access the true intra-patient complexity behind persistent infections involving M. abscessus.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Drug Resistance, Bacterial / genetics
  • Genomics
  • Humans
  • Macrolides
  • Microbial Sensitivity Tests
  • Mycobacterium Infections, Nontuberculous* / microbiology
  • Mycobacterium abscessus*
  • Persistent Infection
  • Phylogeny
  • Reinfection

Substances

  • Anti-Bacterial Agents
  • Macrolides