Enterococcus faecalis is a normal inhabitant of the mammalian intestinal tract, and is not normally pathogenic in healthy humans. However, it has become a major nosocomial pathogen in compromised patients and it can cause a highly fatal form of endocarditis. The medical importance of the enterococci is enhanced by their high degree of inherent resistance to antimicrobial agents, and their propensity to both acquire and to donate novel resistance genes by horizontal transfer. Enterococci are commonly isolated from biofilms formed on implanted medical devices such as catheters and feeding tubes, and colonization and growth on heart valves may represent a form of the biofilm growth state. A recent report suggests the biofilm environment as a likely niche for transfer of high-level vancomycin resistance from enterococci to Staphylococcus aureus. In this project, the physiology and genetics of biofilm formation in E. faecalis will be analyzed using both in vitro and animal models. This work could lead to the identification of novel gene products required for the adaptation of the organisms from a commensal lifestyle to that of a pathogen.
The specific aims of the project are: 1) To identify the E. faecalis genetic determinants required for biofilm formation. 2) To use reporter gene constructs to monitor expression in biofilms, and to characterize the sensing machinery used by E. faecalis to adapt to biofilm growth from planktonic growth. 3) To analyze the cellular and molecular structure of E. faecalis biofilms using high resolution scanning electron microscopy. 4) To test the virulence of selected biofilm-deficient mutants in experimental endocarditis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI058134-03
Application #
7226681
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Peters, Kent
Project Start
2005-07-01
Project End
2010-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$354,382
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Dale, Jennifer L; Nilson, Jennifer L; Barnes, Aaron M T et al. (2017) Restructuring of Enterococcus faecalis biofilm architecture in response to antibiotic-induced stress. NPJ Biofilms Microbiomes 3:15
Frank, Kristi L; Vergidis, Paschalis; Brinkman, Cassandra L et al. (2015) Evaluation of the Enterococcus faecalis Biofilm-Associated Virulence Factors AhrC and Eep in Rat Foreign Body Osteomyelitis and In Vitro Biofilm-Associated Antimicrobial Resistance. PLoS One 10:e0130187
Dale, Jennifer L; Cagnazzo, Julian; Phan, Chi Q et al. (2015) Multiple roles for Enterococcus faecalis glycosyltransferases in biofilm-associated antibiotic resistance, cell envelope integrity, and conjugative transfer. Antimicrob Agents Chemother 59:4094-105
Cook, Laura C C; Dunny, Gary M (2014) The Influence of Biofilms in the Biology of Plasmids. Microbiol Spectr 2:
Frank, Kristi L; Colomer-Winter, Cristina; Grindle, Suzanne M et al. (2014) Transcriptome analysis of Enterococcus faecalis during mammalian infection shows cells undergo adaptation and exist in a stringent response state. PLoS One 9:e115839
Cook, Laura C C; Dunny, Gary M (2014) The influence of biofilms in the biology of plasmids. Microbiol Spectr 2:0012
Leuck, Anne-Marie; Johnson, James R; Dunny, Gary M (2014) A widely used in vitro biofilm assay has questionable clinical significance for enterococcal endocarditis. PLoS One 9:e107282
Frank, Kristi L; Guiton, Pascale S; Barnes, Aaron M T et al. (2013) AhrC and Eep are biofilm infection-associated virulence factors in Enterococcus faecalis. Infect Immun 81:1696-708
Dunny, Gary M (2013) Enterococcal sex pheromones: signaling, social behavior, and evolution. Annu Rev Genet 47:457-82
Cook, L C; Dunny, G M (2013) Effects of biofilm growth on plasmid copy number and expression of antibiotic resistance genes in Enterococcus faecalis. Antimicrob Agents Chemother 57:1850-6

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