The increasing incidence of antibiotic resistance in bacterial pathogens, coupled with a continuing decrease in the rate of introduction of new antimicrobial agents, constitutes one of the most serious problems in modern Medicine. The research carried out under this grant involves the study of the most efficient system for rapid dissemination of resistance determinants known in the bacterium Enterococcus faecalis, a species which is the most important contributor to the emergence of resistance in gram positive bacterial pathogens. This research is focused on the molecular and genetic basis for the ability of a small peptide pheromone produced by plasmid-free cells to induce donor cells carrying the antibiotic resistance plasmid pCF10 to transfer a copy of the plasmid to a recipient. This form of cell-cell communication is highly complex, specific, and efficient. The research proposed in this application will focus on several of the key components involved in control of the pheromone response, and how they function at the molecular level.
The specific aims are as follows: 1. Elucidate the molecular mechanism by which pheromone binding to the pheromone receptor protein PrgX leads to induction of conjugation functions. 2. Determine the mechanism by which the pCF10-encoded Qa regulatory RNA inhibits extension of transcription of the pheromone-inducible conjugative transfer operon. 3. Determine the mechanism of action of PrgY, a novel membrane protein that acts at the cell surface to prevent self-induction in donor cells by endogenously produced, cell-associated pheromone.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM049530-24
Application #
7329819
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Portnoy, Matthew
Project Start
1992-09-01
Project End
2009-11-30
Budget Start
2007-12-01
Budget End
2008-11-30
Support Year
24
Fiscal Year
2008
Total Cost
$294,949
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
Chen, Yuqing; Bandyopadhyay, Arpan; Kozlowicz, Briana K et al. (2017) Mechanisms of peptide sex pheromone regulation of conjugation in Enterococcus faecalis. Microbiologyopen 6:
Dunny, Gary M; Berntsson, Ronnie Per-Arne (2016) Enterococcal Sex Pheromones: Evolutionary Pathways to Complex, Two-Signal Systems. J Bacteriol 198:1556-1562
Bhatty, Minny; Cruz, Melissa R; Frank, Kristi L et al. (2015) Enterococcus faecalis?pCF10-encoded surface proteins PrgA, PrgB (aggregation substance) and PrgC contribute to plasmid transfer, biofilm formation and virulence. Mol Microbiol 95:660-77
Borrero, Juan; Chen, Yuqing; Dunny, Gary M et al. (2015) Modified lactic acid bacteria detect and inhibit multiresistant enterococci. ACS Synth Biol 4:299-306
Cook, Laura C C; Dunny, Gary M (2014) The Influence of Biofilms in the Biology of Plasmids. Microbiol Spectr 2:
Cook, Laura C C; Dunny, Gary M (2014) The influence of biofilms in the biology of plasmids. Microbiol Spectr 2:0012
Johnson, Christopher M; Chen, Yuqing; Lee, Heejin et al. (2014) Identification of a conserved branched RNA structure that functions as a factor-independent terminator. Proc Natl Acad Sci U S A 111:3573-8
Chatterjee, Anushree; Cook, Laura C C; Shu, Che-Chi et al. (2013) Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer. Proc Natl Acad Sci U S A 110:7086-90
Dunny, Gary M (2013) Enterococcal sex pheromones: signaling, social behavior, and evolution. Annu Rev Genet 47:457-82
Berntsson, Ronnie P-A; Schuurman-Wolters, Gea K; Dunny, Gary et al. (2012) Structure and mode of peptide binding of pheromone receptor PrgZ. J Biol Chem 287:37165-70

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