Enterococci rank among most common causes of hospital-acquired infection, making them a leading public health concern. Many of the enterococci that cause these infections are resistant to multiple antibiotics - and with increasing frequency, to all antibiotics. During the 1980's one genetic lineage of E. faecalis emerged that has acquired resistances to all antibiotics and is highly virulent. We and others found members of this lineage to be passed from patient to patient within hospital wards, and from hospital to hospital. Over a quarter of the genome of this E. faecalis lineage consists of acquired mobile DMA. We propose a series of experiments to follow up our description of a pathogenicity island in this virulent, antibiotic resistant lineage of E. faecalis. Initial studies examine the evolution of the PAI in strains collected since the early days of the 20th Century, and are designed to identify its pattern of inheritance and the accretion of traits. The proposed studies then ask about the stability of the element and its rate and mechanism of transfer. In the process, isogenic strains lacking the PAI and plasmids that occur natively will be generated, which then allows comparison of the ability of these strains to acquire new traits to that of other E. faecalis lineages. This tests the hypothesis that the PAI, as well as unlinked genes for vancomycin resistance and b-lactamase production, were independently discovered in one particular E. faecalis lineage because this lineage is prolific at acquiring and exchanging mobile elements. Finally, the availability of isogenic strains permits us to ask whether the PAI confers an advantage either in growth in a complex human Gl tract-derived consortium, or in colonization using a novel Drosophila model. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI072360-01A1
Application #
7319732
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Peters, Kent
Project Start
2007-08-01
Project End
2012-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$437,250
Indirect Cost
Name
Schepens Eye Research Institute
Department
Type
DUNS #
073826000
City
Boston
State
MA
Country
United States
Zip Code
02114
Lieberman, Mia T; Van Tyne, Daria; Dzink-Fox, JoAnn et al. (2018) Long-Term Colonization Dynamics of Enterococcus faecalis in Implanted Devices in Research Macaques. Appl Environ Microbiol 84:
Lebreton, François; Valentino, Michael D; Schaufler, Katharina et al. (2018) Transferable vancomycin resistance in clade B commensal-type Enterococcus faecium. J Antimicrob Chemother 73:1479-1486
Zhang, Sicai; Lebreton, Francois; Mansfield, Michael J et al. (2018) Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium. Cell Host Microbe 23:169-176.e6
Lebreton, François; Manson, Abigail L; Saavedra, Jose T et al. (2017) Tracing the Enterococci from Paleozoic Origins to the Hospital. Cell 169:849-861.e13
Woods, Stephanie E; Lieberman, Mia T; Lebreton, Francois et al. (2017) Characterization of Multi-Drug Resistant Enterococcus faecalis Isolated from Cephalic Recording Chambers in Research Macaques (Macaca spp.). PLoS One 12:e0169293
Van Tyne, Daria; Gilmore, Michael S (2017) Raising the Alarmone: Within-Host Evolution of Antibiotic-Tolerant Enterococcus faecium. MBio 8:
Wurster, Jenna I; Saavedra, José T; Gilmore, Michael S (2016) Impact of Antibiotic Use on the Evolution of Enterococcus faecium. J Infect Dis 213:1862-5
Gaca, Anthony O; Gilmore, Michael S (2016) Killing of VRE Enterococcus faecalis by commensal strains: Evidence for evolution and accumulation of mobile elements in the absence of competition. Gut Microbes 7:90-6
Gaca, Anthony O; Gilmore, Michael S (2016) A lysin to kill. Elife 5:
Varahan, Sriram; Harms, Nathan; Gilmore, Michael S et al. (2014) An ABC transporter is required for secretion of peptide sex pheromones in Enterococcus faecalis. MBio 5:e01726-14

Showing the most recent 10 out of 34 publications