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Work Package 5

Investigating the micro-evolution of E. faecalis isolated in a bacteremia context

Project specific informations

Enterococcus faecalis is a core constituent of the intestinal flora of humans and an important cause of nosocomial infections worldwide. Importantly, the enterococci are a leading cause of hospital-acquired bacteremia that is associated with high mortality when caused by a multi-drug resistant strain1. In 1991, Huycke and collaborators reported a 3 year survey of bloodstream infections due to E. faecalis at the University of Wisconsin Hospital and Clinics. These authors reported that the isolates were closely related and shared a high-level of gentamicin resistance and were able to produce hemolysin2.

In this project, 66 of these gentamicin-resistant E. faecalis strains, isolated during an 18th month period, were sequenced. The central aim of this research is to determine the microevolution of E. faecalis within the host as the microbe spreads among patients in the hospital and in response to the antibiotics used to control the bacteremia. The analyses will be correlated with meta-information, as in vivo selection for antibiotic resistances or patient related information (e.g., antibiotic treatment, cohorting, care team, etc.), collected along with the isolated strains.

Work plan

The genome corresponding to the progenitor strain will be assembled de novo and will serve as a reference. The sequence of subsequent isolates will be compared to the reference and a SNP analysis will be perform, and any other changes in genome sequence will be determined. This will allow us to determine the SNP rate of E. faecalis in the host in an infection context, as described previously in the literature for other genera3 4. The role of the identified SNPs in the evolution of the strain including acquisition of mobile elements and other genetic variations will be further investigated. Importantly, to identify genes that are under selection in E. faecalis during infection, areas of rapid genetic drift will be examined by determining the ratio of the rate of non-synonymous substitutions to the rate of synonymous substitutions. Finally, the relationships between isolates from different patients will be investigated to address the phylogeny and the structure of this E. faecalis population as well as the pattern of transmission as previously described5.

References


  1. Edmond MB, Ober JF, Dawson JD, Weinbaum DL, Wenzel RP. Vancomycin-resistant enterococcal bacteremia: natural history and attributable mortality. Clin Infect Dis. 1996 Dec;23(6):12341239. 

  2. Huycke MM, Spiegel CA, Gilmore MS. Bacteremia caused by hemolytic, high-level gentamicin-resistant Enterococcus faecalis. Antimicrob Agents Chemother. 1991 August; 35(8): 16261634. 

  3. Ford CB, Lin PL, Chase MR, Shah RR, Iartchouk O, Galagan J, Mohaideen N, Ioerger TR, Sacchettini JC, Lipsitch M, Flynn JL, Fortune SM. Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection. Nat Genet. 2011 May;43(5):482-6. 

  4. McAdam PR, Holmes A, Templeton KE, Fitzgerald JR. Adaptive evolution of Staphylococcus aureus during chronic endobronchial infection of a cystic fibrosis patient. PLoS One. 2011;6(9):e24301. 

  5. Lieberman TD, Michel JB, Aingaran M, Potter-Bynoe G, Roux D, Davis Jr. MR, Skurnik D, Leiby N, LiPuma JJ, Goldberg JB, McAdam AJ, Priebe GP, Kishony R. Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes. Nat Genet. 2011 November 13; 43(12): 12751280. 

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)"