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Genomic Analysis Uncovers Population Restructuring Among Hospital Pathogen Isolates

NEW ORLEANS (GenomeWeb) – Using genomic analysis, researchers followed the evolution of a hospital pathogen over the course of nearly a decade, finding that the strain that was common in the early years of the outbreak was replaced by another a few years later.

The prevalence of Acinetobacter baumannii, a common multi-drug resistant pathogen, increased noticeably in 2007 among hospital patients in Cleveland, Mark Adams, the director of Microbial Genomic Services at the Jackson Laboratory for Genomic Medicine, said at the American Society for Microbiology meeting here.

A. baumannii, a soil bacterium, causes infections among hospital patients, especially among those in intensive care. He further noted that just where A. baumannii comes from is unclear.

To examine how the pathogen has been circulating in Cleveland, he and his colleagues from Case Western Reserve University, the Cleveland Clinic, and the J. Craig Venter Institute analyzed nearly 900 A. baumannii isolates collected from University Hospitals and the Cleveland Clinic. They found that there was an extensive overlap of strains between the hospitals and that A. baumannii underwent a major population restructuring in that time.

Adams and his colleagues examined 810 samples from University Hospitals that had been collected between 2007 and 2016, more than 65 percent of which they have sequenced. Most of the samples underwent Illumina shotgun sequencing, though a few were analyzed on a Pacific Biosciences platform.

They also collected 70 recent samples from the Cleveland Clinic for analysis. The two hospitals are about a mile apart, he noted, but have separate feeder hospitals and affiliated physicians, though they share some overlapping long-term care facilities that send patients to them. Adams noted that if hospitals were the main source for A. baumannii, then the two should have distinct populations.

By comparing their isolates to the 1,800 A. baumannii isolates in GenBank, Adams and his colleagues used differences in SNPs in their core genomes to place them on the pathogen's phylogenetic tree. There was, he said, no separation between the University Hospitals and Cleveland Clinic samples. Indeed, there was extensive overlap of the isolates' SNVs and gene content, suggesting that the hospital system wasn't the primary driver of the infections.

At the same time, Adams and his colleagues noticed that the genetic background of their A. baumannii isolates changed over time. Before 2012, their isolates were genetically diverse, but around 2013 that diversity was replaced by a single clade, dubbed clade F.

This replacement was accompanied by a change in resistance genes, Adams said. He added that the armA gene disappeared and was replaced by the aphA6 gene.

All these A. baumannii isolates are multi-drug resistant, and both the armA and aphA6 genes confer resistance, though the shift reflects a change in mechanism behind that resistance. Adams added that they don't know whether drug resistance was driving this replacement in A. baumannii strains or not.

Previously, Adams, then at the J. Craig Venter Institute, reported that A. baumannii appears to amass antibiotic resistance genes, especially genes encoding the beta-lactamase enzyme. Adams also found that most A. baumanni-housed genes encoded the carbapenemase enzyme, though he noted that the bacteria tend to not express them at high levels, meaning that they are sometimes still susceptible to those drugs.

At ASM, Adams noted that Clade F is also associated with virulence genes that  became more prevalent in their research, including hemO, csuE, and TSSM, which are involved in heme oxygenase, pilus assembly, and type VI secretion systems, respectively.

He added that the clade wasn't Cleveland-specific and had been reported in Los Angeles in 2009.

This shift in the genetic background of A. baumannii strains raises further questions about what is driving their population dynamics, Adams said, adding that it justifies further analysis and banking of samples.

"I still really think patients are the reservoir, but that's just supposition," he said.