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Enterococcus I

Enterococci are ubiquitous members of the gastrointestinal tract flora of most mammals, reptiles, birds1 and insects2 3. Although originating as commensals, enterococci currently rank second behind only the staphylococci as leading agents of usually multiple antibiotic resistant health care associated infection (HAI)4. As antibiotic resistant HAI add over $20 billion annually in excess health care costs in the USA5, approximately $2.42 billion, along with ~ 12,000 deaths, can be ascribed to HAI caused by enterococci. Enterococci rank among leading causes of central line associated bloodstream infection (CLABSI), catheter associated urinary tract infection (CAUTI), and surgical site infection4.

Although enterococci are often not speciated in healthcare facilities, historically 75% - 90% of enterococcal infections are found to be caused by the species E. faecalis6 7. Since the entry of vancomycin resistance into clinical isolates in the mid 80s, there has been an increase in E. faecium infection associated with this resistance, bringing them to closer to parity as causes of enterococcal infection5. E. faecium infection appears to be highly dependent on resistance to last line drugs, whereas E. faecalis infection is believed to have a greater innate capacity to cause infection irrespective of resistance6 7. Interestingly, E. faecalis is the primary species that has transmitted vancomycin resistance to S. aureus8.

Project Goals

In this study we compare the 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. Our goal is to identify how multiple resistant strains differ from commensal strains, and to identify 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.

Since E. faecalis is not the only enterococcal species to cause multiple antibiotic resistant infection, we will compare the content and organization of antibiotic resistance genes in this genome with 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:

  1. How are antibiotic resistance traits organized within the genomes of multiple antibiotic resistant enterococcal strains from different MLST types and different enterococcal species?
  2. What traits distinguish infection-related isolates from commensal isolates?
  3. How do pathogenic and commensal lineages of E. faecium differ from each other, and how do they differ from E. faecalis?
  4. What set of genes distinguishes a strain adapted for a human host versus a strain adapted for an animal host, and which genes appear to specifically facilitate colonization of humans?
  5. What traits are common among the rare causes of enterococcal infection, and additionally, what traits constitute the main differences among these species?
  6. What are the genetic differences, and inferred ecologic differences, between motile and non-motile enterococci?

References


  1. Mundt JO. 1963, Occurrence of enterococci in animals in a wild environment. Appl Microbiol. 11:136-40. 

  2. Martin JD, Mundt JO. 1972. Enterococci in insects. Appl Microbiol. 24(4):575-80. 

  3. Cox CR, Gilmore MS. 2007. Native microbial colonization of Drosophila melanogaster and its use as a model of Enterococcus faecalis pathogenesis. Infect Immun. 2007 Apr;75(4):1565-76. 

  4. Alicia I. Hidron, MD; Jonathan R. Edwards, MS; Jean Patel, PhD; Teresa C. Horan, MPH; Dawn M. Sievert, PhD; Daniel A. Pollock, MD; Scott K. Fridkin, MD; for the National Healthcare Safety Network Team and Participating National Healthcare Safety Network Facilities. 2008. NHSN Annual Update- Antimicrobial-Resistant Pathogens Associated With Healthcare-Associated Infections: Annual Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 20062007. Infect Control Hosp Epidemiol 29:996-1011. 

  5. CDC. 2011. Antimicrobial Resistance Posing Growing Health Threat. http://www.cdc.gov/media/releases/2011/p0407_antimicrobialresistance.html 

  6. M M Huycke, C A Spiegel and M S Gilmore. 1991. Bacteremia caused by hemolytic, high-level gentamicin-resistant Enterococcus faecalis. Antimicrob. Agents Chemother. 35:1626-1634 

  7. Mundy LM, Sahm DF, Gilmore M. 2000. Relationships between enterococcal virulence and antimicrobial resistance. Clin Microbiol Rev. 2000 Oct;13(4):513-22. 

  8. Kos VN, Desjardins CA, Griggs A, Cerqueira G, Van Tonder A, Holden MT, Godfrey P, Palmer KL, Bodi K, Mongodin EF, Wortman J, Feldgarden M, Lawley T, Gill SR, Haas BJ, Birren B, Gilmore MS. 2012. Comparative Genomics of Vancomycin-Resistant Staphylococcus aureus Strains and Their Positions within the Clade Most Commonly Associated with Methicillin-Resistant S. aureus Hospital-Acquired Infection in the United States. MBio. 3(3). pii: e00112-12. 

Citation

Please cite all data relating to this initiative (including individual genes and genomes) as:
"Enterococcus I initiative, Broad Institute (broadinstitute.org)"