title: Genomic Analysis of Factors Associated with Low Prevalence of Antibiotic Resistance in Extraintestinal PathogenicEscherichia coliSequence Type 95 Strains.
abstract: Extraintestinal pathogenicEscherichia coli(ExPEC) strains belonging to multilocus sequence type 95 (ST95) are globally distributed and a common cause of infections in humans and domestic fowl. ST95 isolates generally show a lower prevalence of acquired antimicrobial resistance than other pandemic ExPEC lineages. We took a genomic approach to identify factors that may underlie reduced resistance. We fully assembled genomes for four ST95 isolates representing the four majorfimH-based lineages within ST95 and also analyzed draft-level genomes from another 82 ST95 isolates, largely from the western United States. The fully assembled genomes of antibiotic-resistant isolates carried resistance genes exclusively on large (>90-kb) IncFIB/IncFII plasmids. These replicons were common in the draft genomes as well, particularly in antibiotic-resistant isolates, but we also observed multiple instances of a smaller (8.3-kb) ampicillin resistance plasmid that had been previously identified inSalmonella enterica. Among ST95 isolates, pansusceptibility to antibiotics was significantly associated with thefimH6lineage and the presence of homologs of the previously identified 114-kb IncFIB/IncFII plasmid pUTI89, both of which were also associated with reduced carriage of other plasmids. Potential mechanistic explanations for lineage- and plasmid-specific effects on the prevalence of antibiotic resistance within the ST95 group are discussed.IMPORTANCEAntibiotic resistance in bacterial pathogens is a major public health concern. This work was motivated by the observation that only a small proportion of ST95 isolates, a major pandemic lineage of extraintestinal pathogenicE. coli, have acquired antibiotic resistance, in contrast to many other pandemic lineages. Understanding bacterial genetic factors that may prevent acquisition of resistance could contribute to the development of new biological, medical, or public health strategies to reduce antibiotic-resistant infections.
authors.affiliation: Biology Department and Public Health Program, Santa Clara University, Santa Clara, California, USA.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Stephens
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California, USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Adams-Sapper
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California, USA.
authors.forename: Manraj
authors.initials: M
authors.lastname: Sekhon
authors.affiliation: Veterans Affairs Medical Center and University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Johnson
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California, USA.
authors.forename: Lee W
authors.initials: LW
authors.lastname: Riley
keywords: Escherichia coli; ExPEC; ST95; antibiotic resistance; genomics