Rapid Replacement of Acinetobacter baumannii Strains Accompanied by Changes in Lipooligosaccharide Loci and Resistance Gene Repertoire

Abstract

The population structure of health care-associated pathogens reflects patterns of diversification, selection, and dispersal over time. Empirical data detailing the long-term population dynamics of nosocomial pathogens provide information about how pathogens adapt in the face of exposure to diverse antimicrobial agents and other host and environmental pressures and can inform infection control priorities. Extensive sequencing of clinical isolates from one hospital spanning a decade and a second hospital in the Cleveland, OH, metropolitan area over a 3-year time period provided high-resolution genomic analysis of the Acinetobacter baumannii metapopulation. Genomic analysis demonstrated an almost complete replacement of the predominant strain groups with a new, genetically distinct strain group during the study period. The new group, termed clade F, differs from other global clone 2 (GC2) strains of A. baumannii in several ways, including its antibiotic resistance and lipooligosaccharide biosynthesis genes. Clade F strains are part of a large phylogenetic group with broad geographic representation. Phylogenetic analysis of single-nucleotide variants in core genome regions showed that although the Cleveland strains are phylogenetically distinct from those isolated from other locations, extensive intermixing of strains from the two hospital systems was apparent, suggesting either substantial exchange of strains or a shared, but geographically restricted, external pool from which infectious isolates were drawn. These findings document the rapid evolution of A. baumannii strains in two hospitals, with replacement of the predominant clade by a new clade with altered lipooligosaccharide loci and resistance gene repertoires.IMPORTANCE Multidrug-resistant (MDR) A. baumannii is a difficult-to-treat health care-associated pathogen. Knowing the resistance genes present in isolates causing infection aids in empirical treatment selection. Furthermore, knowledge of the genetic background can assist in tracking patterns of transmission to limit the spread of infections in hospitals. The appearance of a new genetic background in A. baumannii strains with a different set of resistance genes and cell surface structures suggests that strong selective pressures exist, even in highly MDR pathogens. Because the new strains have levels of antimicrobial resistance similar to those of the strains that were displaced, we hypothesize that other features, including host colonization and infection, may confer additional selective advantages and contribute to their increased prevalence.

Keywords: Acinetobacter; antibiotic resistance; genome analysis.

FIG 1

Phylogenetic tree of A. baumannii global clone 2 isolates. A phylogenetic tree was constructed using a core set of SNVs present in GC2 genomes. The rings of annotation extending outward from the inner ring depict clade, Oxford MLST type; year of isolation; K locus; OC locus; the presence of a pABUH1-like plasmid; OXA-23; the ISAba1-bla_OXA insertion; Tn2006; AphA6; AphA1; the HUMC1-type integron; AadB; AadA2; the TCDC-AB7015-type integron; AacC1; AadA1; ArmA; two alternative PilA alleles, A-type PilA (GenBank accession number WP_000993717.1) and B-type PilA (GenBank accession number WP_000993718.1); two alternative PglC alleles, A-type PglC (GenBank accession number WP_000826956.1) and B-type PglC (GenBank accession number WP_000977704.1); and isolation location.

FIG 2

Change in clade abundance over time. The proportions of A. baumannii isolates from hospital system A (A) and hospital system B (B) belonging to each major clade are shown, grouped by the year in which they were isolated. The number of isolates per year is shown as a black dotted line, with units provided on the secondary axis (n = 443 for UH strains and n = 70 for CC strains).

FIG 3

Integron structures in clade F strains. (A) A complex transposon structure was inserted into the HUMC1 genome at coordinates 1513187 to 1528810 (GenBank accession number LQRQ01000007.1). A partial deletion of this region was found at the corresponding location in the GC1 strain AB0057 and in other GC2 strains, including TYTH-1, ACICU, and the clade F strain UH7007. Most clade F genomes carried only the integron (labeled “b”) and not the Tn6020 segment (labeled “a”) from HUMC1. Yellow arrows indicate copies of IS26. (B) Gene diagram corresponding to the region in purple in panel A. (C) The complex transposon structure from ABUH585 and other clade F genomes. This region is similar to the integron present in the TCDC-AB0715 genome at bases 274173 to 281008 under GenBank accession number CP002522.2. Resistance genes are in purple. The * gene in panel B is qacEΔ1.

FIG 4

Variation in the OCL locus among clade F strains. The inferred genetic structure of the OCL locus is shown, with variants present in different genomes. The OCL3 locus from GenBank accession number KC118540.6 is shown. Asterisks denote the locations of IS element insertions in a subset of genomes. The OCL3 variants found among clade F genomes are depicted, along with the number of genomes in which the variant was observed.