Protected environments allow parallel evolution of a bacterial pathogen in a patient subjected to long-term antibiotic therapy

A. S. Low, Fiona MacKenzie, Ian M Gould, Ian Rylance Booth

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Long-term antibiotic treatment offers a rare opportunity to study the evolution of bacteria within the same individual. The appearance of new variants has been suggested to take place via the selection of enhanced resistance in compartments of the body in which the antibiotic concentration is low. Laboratory models of protected compartments have elegantly demonstrated their potential in selecting novel variants. However, comparable data from patients have been rare. In this study, extended antibiotic therapy in a single patient suffering from multiple infected liver cysts has provided the opportunity to observe and analyse the molecular evolution of antibiotic resistance. Each isolate has the same basic ompC gene sequence that is distinct from other Escherichia coli isolates, which suggests that they derive from the same founder population. However, the isolates differ in their auxotrophic markers, in the pl values of their dominant P-lactamase activities and in the mutations in the promoter region of the ampC gene leading to increased expression of the AmpC enzyme. The data provide strong evidence for a single focal infection expanding via parallel pathways of evolution to give a range of anti biot ic-resistant isolates. These data suggest that the infected cysts provide numerous protected environments that are the foci for the separate development of distinct variants.

Original languageEnglish
Pages (from-to)619-630
Number of pages11
JournalMolecular Microbiology
Volume42
Issue number3
DOIs
Publication statusPublished - 2001

Keywords

  • NONENCAPSULATED HAEMOPHILUS-INFLUENZAE
  • OUTER-MEMBRANE PROTEIN
  • ESCHERICHIA-COLI
  • PSEUDOMONAS-AERUGINOSA
  • CYSTIC-FIBROSIS
  • BETA-LACTAMASE
  • NEISSERIA-MENINGITIDIS
  • HELICOBACTER-PYLORI
  • ADAPTIVE EVOLUTION
  • BIOLOGICAL COST

Cite this