Genomic transition of enterococci from gut commensals to leading causes of multidrug-resistant hospital infection in the antibiotic era

Abstract

The enterococci evolved over eons as highly adapted members of gastrointestinal consortia of a wide variety of hosts, but for reasons that are not entirely clear, emerged in the 1970s as leading causes of multidrug resistant hospital infection. Hospital-adapted pathogenic isolates are characterized by the presence of multiple mobile elements conferring antibiotic resistance, as well as pathogenicity islands, capsule loci and other variable traits. Enterococci may have been primed to emerge among the vanguard of antibiotic resistant strains because of their occurrence in the GI tracts of insects and simple organisms living and feeding on organic matter that is colonized by antibiotic resistant, antibiotic producing micro-organisms. In response to the opportunity to inhabit a new niche--the antibiotic treated hospital patient--the enterococcal genome is evolving in a pattern characteristic of other bacteria that have emerged as pathogens because of opportunities stemming from anthropogenic change.

Figure 1

Dendrogram of the genus Enterococcus. A dendrogram of all available 16S rDNA sequences for members of the Enterococcus genus was compiled using the Geneious software (Biomatters Ltd) using the neighbour-joining algorithm and the 16S sequence of Tetragenococcus solitarius as an outgroup. Boostrap values were generated over 1000 iterations. The species E. faecalis and E. faecium are highlighted in blue.

Figure 2

Microevolution of the E. faecalis pathogenicity island showing the basis for variation between PAI copies in CC2 strains MMH594, V583 and V586 (35). MMH594 is a highly virulent clone that caused approximately 85 E. faecalis bacteremias over a 17 month period (17). V583 and V586 were obtained from the bloodstream of a chronically infected patient (21), and show a process of steady attenuation common in strains associated with chronic infection. In evolving from the prototype PAI of MMH594, IS expansion occurred resulting in new insertions of IS256 and IS905 in strain V586, followed by high frequency excision of a 17 kb fragment encoding half of the cytolysin operon and the esp gene (35). Adapted from (35).

Figure 3

Comparative mobile element content of the genomes of the commensal-like strain OG1RF, and the hospital-adapted strain V583. (V583 diagram adapted from (38)).