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Work Package 6

A genomic perspective on evolution and niche-adaptation of Enterococcus faecalis

Project specific informations

Enterococcus faecalis is a core constituent of the intestinal flora of humans and a leading cause of nosocomial infections worldwide. The ability of E. faecalis to cause serious infection is due to its inherent capability to persist in the hospital environment, survive host defenses, damage the host cells through various virulence determinants and resist various antibiotics like vancomycin1 2. However, E. faecalis is also the predominant species of the Enterococcus genus in various animals (insects, reptiles, birds and mammals) and in other environments (water, plants and fermented food)3 4. Previous comparative genome studies highlighted the diversity of this species and the importance of mobile genetic elements in the evolution of the Enterococcus genus5 6. In addition, we recently reported the role of CRISPR elements in the evolution of E. faecalis from commensal to hospital-adapted, multi-drug resistant organism and the first description of the genetic basis for daptomycin resistance in enterococci7 8. In this current study, we will examine 89 E. faecalis genomes representing strains from a variety of niches, hosts and countries between the 1900s and 2006, and representing the full breadth of Multi Locus Sequence Types (MLST). These newly sequenced strains expand upon the 16 E. faecalis strains previously analyzed from the collection reported in 20075 9. Through this study, we aim to better understand the mechanisms of host adaptation and the emergence of antibiotic resistance by determining the relatedness among strains and correlating strain-specific meta-information including drug resistance profiles and site of isolation. This study will also lead to the identification of genes and genetic elements that play a role in the adaptation of E. faecalis to different environments.

Work plan

Divergence among isolates will be examined using a SNP-based phylogenomic approach based on the E. faecalis core genome that will take into account recombination10. This will improve upon the previously published phylogeny5. In addition, we will quantify diversity using:

  • pan-genome analyses to estimate E. faecalis capacity to incorporate genetic material in its genome
  • gene content and metabolic pathway analyses to determine how gain and loss of specific genes and pathways influences E. faecalis adaptation to different niches
  • comparative analyses of mobile genetic elements including the pathogenicity island carrying the esp gene11, plasmids, bacteriophages and others genomic islands to understand how these elements influence host adaptation
  • CRISPR comparative analyses
  • whole genome analyses that report signatures of positive or purifying selection that can explain niche adaptation and drug resistance among E. faecalis

References


  1. Pillar CM, Gilmore MS. Enterococcal virulence–pathogenicity island of E. faecalis. Front Biosci. 2004 Sep 1;9:2335-46. Review. 

  2. Arias CA, Murray BE. The rise of the Enterococcus: beyond vancomycin resistance. Nat Rev Microbiol. 2012 Mar 16;10(4):266-78. 

  3. Gilmore MS, Clewell DB, Courvalin P, Dunny GM, Murray BE, Rice LB. The Enterococci: Pathogenesis, Molecular Biology, and Antibiotic Resistance. ASM Press, Washington, D.C. 2002 

  4. Franz CM, Stiles ME, Schleifer KH, Holzapfel WH. Enterococci in foods, a conundrum for food safety. Int J Food Microbiol. 2003 Dec 1;88(2-3):105-22. Review. 

  5. 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. 

  6. 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. 

  7. Palmer KL, Gilmore MS. Multidrug-resistant enterococci lack CRISPR-cas. MBio. 2010 Oct 12;1(4). pii: e00227-10. 

  8. Palmer KL, Daniel A, Hardy C, Silverman J, Gilmore MS. Genetic basis for daptomycin resistance in enterococci. Antimicrob Agents Chemother. 2011 Jul; 55(7):3345-56. Epub 2011 Apr 18. 

  9. McBride SM, Fischetti VA, Leblanc DJ, Moellering RC Jr, Gilmore MS. Genetic diversity among Enterococcus faecalis. PLoS One. 2007 Jul 4;2(7):e582. 

  10. Marttinen P, Hanage WP, Croucher NJ, Connor TR, Harris SR, Bentley SD, Corander J. Detection of recombination events in bacterial genomes from large population samples. Nucleic Acids Res. 2012 Jan;40(1):e6. Epub 2011 Nov 7. 

  11. McBride SM, Coburn PS, Baghdayan AS, Willems RJ, Grande MJ, Shankar N, Gilmore MS. Genetic variation and evolution of the pathogenicity island of Enterococcus faecalis. J Bacteriol. 2009 May;191(10):3392-402. Epub 2009 Mar 6. 

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 II initiative, Broad Institute (broadinstitute.org)"