New Insights into Dissemination and Variation of the Health Care-Associated Pathogen Acinetobacter baumannii from Genomic Analysis

Abstract

Acinetobacter baumannii is a globally important nosocomial pathogen characterized by an increasing incidence of multidrug resistance. Routes of dissemination and gene flow among health care facilities are poorly resolved and are important for understanding the epidemiology of A. baumannii, minimizing disease transmission, and improving patient outcomes. We used whole-genome sequencing to assess diversity and genome dynamics in 49 isolates from one United States hospital system during one year from 2007 to 2008. Core single-nucleotide-variant-based phylogenetic analysis revealed multiple founder strains and multiple independent strains recovered from the same patient yet was insufficient to fully resolve strain relationships, where gene content and insertion sequence patterns added additional discriminatory power. Gene content comparisons illustrated extensive and redundant antibiotic resistance gene carriage and direct evidence of gene transfer, recombination, gene loss, and mutation. Evidence of barriers to gene flow among hospital components was not found, suggesting complex mixing of strains and a large reservoir of A. baumannii strains capable of colonizing patients.

A multidrug resistance plasmid contains the molecular switch for type VI secretion in Acinetobacter baumannii

“…However, our data suggest that A. baumannii loses this plasmid readily without antibiotic selection, indicating plasmid loss is a true mechanism for T6SS activation. In the human host, plasmid loss has been documented in A. baumannii strains isolated from the same patient over time (35). Furthermore, the finding that this plasmid can be conjugated from a T6-cell to a T6+ cell raises the possibility that the plasmid can be disseminated back into those cells that have lost it.…”

“…Under conditions where antibiotics are present, MDR A. baumannii may derive enough of a survival advantage from antibiotic resistance alone that an active T6SS is neither necessary nor beneficial (35). In fact, genome sequencing of several recent MDR A. baumannii isolates revealed that some lack a full T6SS locus, suggesting some strains have inactivated their secretion system in favor of antibiotic resistance (35,38,39). The plasmid present in the old isolate Ab 17978 strain encodes a single antibiotic resistance.…”

Utility of Whole-Genome Sequencing in Characterizing Acinetobacter Epidemiology and Analyzing Hospital Outbreaks

“…The inclusion of the strain types for the relevant Acinetobacter species within these phylogenies would allow for easy assignment of an individual isolate to a species. Although not examined in this study, WGS can also provide ancillary information, such as the presence or absence of virulence factors and antibiotic resistance islands, which are important for developing effective and timely treatment strategies (74,86). In contrast, the band-based technique Rep-PCR was not able to separate ACB complex isolates into distinct species.…”

“…Clade C (ST406) is most closely related to IC-I strains, although the tight clustering of the clade C isolates and the phylogenetic distance separating them from the IC-I reference strains suggest that clade C may be a distinct clonal group. Clade A (ST79) isolates do not clearly cluster with any reported IC lineage but are closely related to published strains from the United States and other parts of the world (74)(75)(76)(77). Group D (ST499) represents a collection of isolates distinct from known clonal lineages or reported strains.…”

“…A phylogenetic analysis based on WGS also clustered the majority of A. baumannii strains into four groups corresponding to these STs. ST2 (clade B) is part of the IC-II lineage, which is widely prevalent throughout Europe and the United States and is frequently implicated in nosocomial outbreaks (20,74,75). ST406 (clade C) was first reported in an epidemiological study of CRAB clinical isolates from Japan (87) and was subsequently identified in Brazil (88).…”