Enterococcus group Database
Enterococcus spp. serve as a key reservoir of antibiotic resistance genes, and they disseminate these genes to other species. Enterococci have transferred resistance to the last line antibiotic, vancomycin, to methicillin-resistant Staphylococcus aureus, creating a pan-resistant 'superbug'. Enterococci themselves have emerged as leading causes of multiple antibiotic resistant hospital-acquired infection. Despite this medical importance, few enterococcal isolates have been sequenced with an accessible, annotated database. This project examines the organization of antibiotic resistance genes in enterococcal genomes, as well as those genes that may distinguish infection-related isolates from commensal isolates.
Enterococci are among the most antibiotic resistant bacterial pathogens known. For reasons not well understood, they appear to have served as a key collection point for a wide variety of antibiotic resistance determinants, and they disseminate these to other species. Recently it was shown that enterococci have transferred resistance to the last line antibiotic, vancomycin, to methicillin-resistant Staphylococcus aureus. Enterococci themselves have emerged as leading causes of multiple antibiotic resistant hospital-acquired infection. The strains of Enterococcus that cause multiple antibiotic resistant infections cluster into groups by MultiLocus Sequence Typing (MLST), and are genetically distinct from strains that colonize the gastrointestinal tracts of healthy individuals in the community. In addition to possessing resistances to multiple antibiotics (and with the emergence of vancomycin resistance, to all antibiotics), highly pathogenic strains often possess a set of genes that contribute to virulence.
Only one enterococcal isolate, Enterococcus faecalis strain V583, has been fully sequenced with an accessible, annotated database. The genome is comparatively small at 3 Mb (as are those of other enterococcal species), and one quarter consists of mobile genetic elements, including antibiotic resistance plasmids, transposons and a large pathogenicity island, underscoring the potential for genomic variability between enterococcal strains. We propose to compare genomes of clinical isolates of multiple antibiotic resistant enterococcal strains to each other, and to those of commensal enterococci from healthy individuals in the community, with the goal of identifying how multiple resistant strains differ from commensal strains, and of identifying possible intermediates in the process that may illuminate mechanisms that lead to the emergence of multiple resistant strains. Further, since enterococci colonize the GI tracts of all mammals studied, including animals from agricultural settings where antibiotics are applied, as well as insects exposed to antibiotic producing soil organisms, the hypothesis will be tested that these enterococci are the vectors for antibiotic resistances that occur in human strains.
E. faecalis is not the only enterococcal species to cause multiple antibiotic resistant infection. Therefore, the content and organization of antibiotic resistance genes in the genomes of E. faecalis strains will be compared to those of other antibiotic resistant, disease-causing enterococcal species, including E. faecium, E. gallinarum, and E. casseliflavus. The data gathered from these efforts will provide key insights into the emergence and acquisition of antibiotic resistance in a species that appears to serve as a gathering point for these traits.
The specific questions that will be addressed by comparative genomic analysis of the proposed enterococcal strains are:
- How are antibiotic resistance traits organized within the genomes of multiple antibiotic resistant enterococcal strains from different MLST types and different enterococcal species?
- What traits distinguish infection-related isolates from commensal isolates?
- How do pathogenic and commensal lineages of E. faecium differ from each other, and how do they differ from E. faecalis?
- What set of genes distinguishes a strain adapted for a human host versus a strain adapted for another animal host, and which appear to specifically facilitate colonization of humans?
- What traits are common among the rarer causes of enterococcal infection, and additionally, what traits constitute the main differences among these species?
- What are the genetic differences, and inferred ecologic differences, between motile and non-motile enterococci?
- Michael Gilmore, Schepens Eye Research Institute and Harvard Medical School
- Karen Carniol, Schepens Eye Research Institute and Harvard Medical School
- Janet Manson, Schepens Eye Research Institute and Harvard Medical School
- Kelli Palmer, Schepens Eye Research Institute and Harvard Medical School
Photo credits and captions
For the images in the home page, from left to right:
- Scanning Electron Micrograph of Enterococcus faecalis; Pete Wardell at CDC
- Scanning Electron Micrograph of Enterococcus species; Janice Haney Carrat at CDC
- This scanning electron micrograph (SEM) depicted numbers of bacteria, which were identified as being Gram-positive Enterococcus sp. bacteria. Previously identified as "Group D" Streptococcus organisms, the most clinically relevant of these bacteria are, E. faecalis, and E. faecium. Janice Haney Carr at CDC
- Scanning Electron Micrograph of Enterococcus species.; Janice Haney Carr at CDC