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.

Capsule carbohydrate structure determines virulence in Acinetobacter baumannii

“…These results follow the molecular Koch's postulates modified for loss-of-function driving virulence [20], indicating that the bacterial capsule is a primary driver of virulence, as demonstrated across multiple clinical isolates and isogenic strain pairs. BLAST analysis confirmed that this insertion element has previously been characterized as ISAba13 and is present in a variety of A. baumannii clinical isolates, and other work confirms that frequent transposonmediated disruption of genes contributes significantly to A. baumannii virulence in the form of outer molecule structural variation [21], metabolic function, and antimicrobial resistance [22,23].…”

Comparison of the Clinical Characteristics of Hospital-Acquired and Non-Hospital-Acquired Acinetobacter calcoaceticus-baumannii Complex in a Large Midwest US Health Care System

“…Nevertheless, the decrease in HA respiratory, urinary, and blood isolates to near-0 levels unmasked an endemic occurrence of nHA isolates with epidemiologic features similar to nHA isolates from non-BJC1 hospitals (ie, urinary and SST/MSK isolates with ~40% CRAb rates). Consistent with the existence of nHA reservoirs, genomic analysis of A. baumannii isolates in another US Midwest medical center suggested that transmissible isolates at 2 independent hospitals originated from a single, external, nonhospital pool [13]. The location of outpatient Abc pools, their trafficking into hospital environments, and the impact of nHA strains on local Abc disease require further investigation.…”

A New Twist: The Combination of Sulbactam/Avibactam Enhances Sulbactam Activity against Carbapenem-Resistant Acinetobacter baumannii (CRAB) Isolates

“…clinical strains were used to test sulbactam or sulbactam in combination with avibactam or relebactam ( Table S1 ). Among the included strains 152 were A. baumannii , including previously well-characterized strains such as AB5075, AB0057 and ABUH702 [ 40 , 41 , 42 ], and 35 corresponded to non- baumannii species. Among these isolates, 4 were non-ESBL/non-CRAB, 7 were ESBL producing, while 176 were carbapenem-resistant strains.…”