title: Protected environments allow parallel evolution of a bacterial pathogen in a patient subjected to long-term antibiotic therapy.
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 pI values of their dominant beta-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 antibiotic-resistant isolates. These data suggest that the infected cysts provide numerous protected environments that are the foci for the separate development of distinct variants.
authors.affiliation: Department of Molecular and Cell Biology, University of Aberdeen, Institute of Medical Sciences, Aberdeen AB25 2ZD, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Low
authors.forename: F M
authors.initials: FM
authors.lastname: MacKenzie
authors.forename: I M
authors.initials: IM
authors.lastname: Gould
authors.forename: I R
authors.initials: IR
authors.lastname: Booth
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins; D001483:Base Sequence; D016767:Caroli Disease / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D004927:Escherichia coli Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D019143:Evolution, Molecular; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D018272:Porins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013997:Time Factors; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C113724:OmpC protein; D018272:Porins; C048795:AmpC beta-lactamases; D001618:beta-Lactamases