Accepted postdoctoral position in Infectious Diseases at The M.D. Anderson Cancer Center after receiving PhD
Enterococci are currently among the leading causes of hospital-acquired infections in the United States. The basis for the recent transition of E. faecium from a primarily commensal organism to an opportunistic pathogen is not yet understood. Assessment of isolates from early USA outbreaks and outbreaks in South America showed that clinical isolates possess virulence and antibiotic resistance determinants that are not present in community isolates. One observation was that the level of ampicillin resistance increased over time in the hospital-associated strains analyzed. Although there was ~5% difference in the pbp5 gene between susceptible (≤4ug/ml) strains and all other strains, no specific sequence variation correlated with specific increases in MICs in strains with MICs >4ug/ml. This nucleotide difference was also seen in three other genes, which led to the analyses of concatenated core gene sequences, SNPs, and 16S rRNA of 21 E. faecium genomes. These studies along with phylogenetic analysis pointed to the existence of two subpopulations of E. faecium, a community-associated (CA) clade and hospital-associated (HA) clade. Molecular clock calculations indicate that these two clades may have diverged ~ 300,000 to > 1 million years ago, long preceding the modern antibiotic era. In addition to core genomic differences, HA clonal lineages harbor specific genetic elements which may confer selection advantages over the more heterogeneous enterococcal CA E. faecium isolates. Further analysis searching for putative surface proteins, adhesins, and virulence factors discovered 6 genes with the newly identified “WxL” domain. Analyses indicate that E. faecium WxL genes exist in putative operons and encode bacterial cell surface localized proteins. Proteins encoded by these operons can bind a number of different host extracellular matrix proteins, as well as to each other, suggesting a novel cell-surface complex. Proteins with the “WxL” domain seem to be more exposed on the surface of clinical isolates versus community isolates, even though they are present in both subpopulations. The data also indicate that WxL proteins are antigenic in humans and may be involved in bile salt stress.
Molecular and genomic based insights into Enterococcus faecium’s evolution from commensal to hospital-adapted pathogen