Friend turned foe: evolution of enterococcal virulence and antibiotic resistance

Abstract

The enterococci are an ancient genus that evolved along with the tree of life. These intrinsically rugged bacteria are highly adapted members of the intestinal consortia of a range of hosts that spans the animal kingdom. Enterococci are also leading opportunistic hospital pathogens, causing infections that are often resistant to treatment with most antibiotics. Despite the importance of enterococci as hospital pathogens, the vast majority live outside of humans, and nearly all of their evolutionary history took place before the appearance of modern humans. Because hospital infections represent evolutionary end points, traits that exacerbate human infection are unlikely to have evolved for that purpose. However, clusters of traits have converged in specific lineages that are well adapted to colonize the antibiotic-perturbed gastrointestinal tracts of patients and that thrive in the hospital environment. Here we discuss these traits in an evolutionary context, as well as how comparative genomics is providing new insights into the evolution of the enterococci.

Keywords: Enterococcus; genomics; human-associated microbial flora.

Figure 1

Simplified tree of eukaryotic life, with blue shading indicating animals with which enterococci have been found to be associated. The labels to the left of the tree show approximate geologic periods.

Figure 2

Phylogenetic tree of the genus Enterococcus. Available 16S rRNA gene sequences for each species were compiled using Geneious software (Biomatters, Ltd., San Francisco, California) with a neighbor-joining algorithm. The 16S rRNA sequence of Vagococcus lutrae was used as an outgroup. Bootstrap values are shown for nodes with more than two branches and were generated over 1,000 iterations.

Figure 3

Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas loci and acquired antibiotic resistances in Enterococcus faecalis. Strains are ordered by date of isolation, from oldest to most recent, and approximate decades of isolation are shown to the left of the strain names. Presence of acquired antibiotic resistances is shown with orange shading, and CRISPR/Cas locus presence is shown in blue. Only strains containing an acquired antibiotic resistance or a CRISPR/Cas locus are included. Antibiotic resistances were profiled in Reference 74 and correspond to the following compounds: tetracycline (tetM and tetL), chloramphenicol (cat), gentamicin (aac-aph), erythromycin (ermB), ampicillin (blaZ), and vancomycin (vanA/B). Figure is adapted from Reference 87.

Figure 4

(a) Unrooted Bayesian phylogeny of translated vanA sequences analyzed in Reference 25. Blue denotes strains with VanHAX clusters confirmed to confer resistance to vancomycin; sequences containing stop codons but homology throughout are noted with a single asterisk. The scale bar represents 0.1 substitutions per site. Panel is reproduced from Reference 25. (b) Number of patients and cumulative percentage of New York City (NYC) hospitals with vancomycin-resistant enterococci infection between 1989 and 1991. Panel is reproduced from Reference 35.

Figure 5

RAxML (113) single-nucleotide-polymorphism-based tree based on concatenated alignments of DNA sequences of 1,344 single-copy core genes in 73 Enterococcus faecium genomes. Bootstrapping was performed with 1,000 replicates. The origins of the strains and the dates for the split between the clades, estimated by BEAST analysis (29), are indicated. The infectivity score reflects the number of strains of a particular sequence type, in the MLST database, isolated from infection. Three clades are highlighted: B in blue, A1 in red, and A2 in grey. Figure is reproduced from Reference 61.