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EnteroGenome

Comparative analysis of Enterococcus genomes

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.

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 most antibiotics, highly pathogenic strains often possess a pathogenicity island and other genes that contribute to a destabilized host/microbe relationship.

Project goals

The EnteroGenome study was designed to examine and compare the genomes of multiple antibiotic resistant hospital adapted lineages of enterococci to each other, and to commensal strains from healthy individuals, to illuminate the selection pressures and mechanisms that led to the emergence of the problematic multiple resistant hospital strains. Since many of the mobile elements that have accumulated in hospital adapted strains appear to have come from low GC gram-positive bacteria9 10, it was of interest to examine the genomes of other enterococcal species – both to determine what is common to all members of this genus, and also to determine whether some of the factors viewed as contributing to virulence of hospital strains originated as adaptive modules in other related species. To answer these questions the genomes of representatives of most species of Enterococcus, as well as clinical and commensal isolates of the leading causes of enterococcal infection, will be sequenced, examined and compared. 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. A total of 408 enterococcal genomes will be sequenced. The strains of which the genomes are sequenced have been provided by a number of research groups around the world, making this a community effort.

Study organization

This project is a basis for multiple international collaborations as described in the following work packages (WP) that constitute the EnteroGenome project:

Work Package 1
A genomic perspective on evolution and niche-adaptation of Enterococcus faecium
Work Package 2
Comparative genome analysis of Enterococcus genus
Work Package 3
Investigating the microevolution of E. faecalis serially isolated in a bacteremia context
Work Package 4
Survey on antibiotic resistances determinants in E. faecalis and E. feacium
Work Package 5
Microevolution of E. faecalis serial isolates during an epidemic rise in a North-American Hospital
Work Package 6
Genomic perspective on evolution and niche adaptation of E. faecalis
Work Package 7
A genomic survey of vancomycin-resistant E. faecium isolated from swine
Work Package 8
A comparative analysis of Enterococci from animal and human reservoirs in Europe

Project Data can also be found at NCBI

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. 

  9. Paulsen IT, Banerjei L, Myers GS, Nelson KE, Seshadri R, Read TD, Fouts DE, Eisen JA, Gill SR, Heidelberg JF, Tettelin H, Dodson RJ, Umayam L, Brinkac L, Beanan M, Daugherty S, DeBoy RT, Durkin S, Kolonay J, Madupu R, Nelson W, Vamathevan J, Tran B, Upton J, Hansen T, Shetty J, Khouri H, Utterback T, Radune D, Ketchum KA, Dougherty BA, Fraser CM. Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus faecalis. Science. 2003 Mar 28;299(5615):2071-4. 

  10. Palmer KL, Godfrey P, Griggs A, Kos VN, Zucker J, Desjardins C, Cerqueira G, Gevers D, Walker S, Wortman J, Feldgarden M, Haas B, Birren B, Gilmore MS. Comparative genomics of enterococci: variation in Enterococcus faecalis, clade structure in E. faecium, and defining characteristics of E. gallinarum and E. casseliflavus. MBio. 2012 Mar 1;3(1):e00318-11. 

Bermuda principles and public data release

Our goal is to make the genome sequence of organisms rapidly and broadly available to the scientific community. The genome sequencing community recently adopted a statement of principles for the distribution and acceptable uses of large-scale sequencing data. It is our intention to publish the work of this project in a timely fashion, and we welcome collaborative interaction on the project and analyses.

Citation

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