Enterococcus faecalis is a bacterium found in the intestine of humans as well as in a wide variety of ecological niches. While it is not as virulent as Staphylococcus aureus, it resistance to antibiotics and the ease of its spread among its population has long made E. faecalis a serious therapeutic problem. Our proposed research will examine the mechanism employed for the spread of antibiotic resistance in E. faecalis. The antibiotic resistance gene resides in a plasmid. Different plasmids in the same family carry resistance to different antibiotics. However, each cell does not carry every plasmid, as doing so would increase the metabolic load beyond the point of efficiency. Therefore, each type of plasmid must be spread between cells as necessary. The antibiotic resistant plasmid is spread through a direct cell-cell contact process called conjugation, a process in which the donor cells pass the plasmid with the antibiotic resistance gene to recipient cells. The plasmid carried by donor cells encodes the genes for conjugative transfer of the plasmid as well as for a signal peptide. Upon receipt of the plasmid, the recipient cells then become donor cells. The signal peptide produced by the recipient has long been considered a """"""""mate"""""""" sensing molecule for donors to sense the concentration of recipients. Results from our current work using plasmid pCF10 led us to propose that the plasmid encoded signal is a """"""""self"""""""" (or quorum) sensing molecule for donor to sense its own concentration. We hypothesize that through the interplay of the two signaling molecules, the donor and recipient cells alter their conjugative dynamics to maintain their plasmid-present antibiotic resistant subpopulation and plasmid- free, faster growing recipient subpopulation. We further hypothesize that a heterogeneous response to the """"""""mate"""""""" signal by donor cells in a population provides a competitive advantage;to preserve resources, some donor cells respond earlier and at a low concentration of signaling molecules while others respond later and at a higher concentration of signaling molecules. The titration of the cellular response is mediated by two operons in the plasmid. In our current work we have unveiled a noble mechanism which cells employ to respond to the two signaling molecules. In this proposed research we will develop mathematical models to explore the donor-recipient dynamics. A better understanding of the mechanism of plasmid transfer will help us identify a new way to fight conjugative antibiotic resistance transfer.

Public Health Relevance

Bacterial antibiotic resistance often spreads through conjugative plasmid transfer. The subject of this particular study, Enterococcus faecalis, is a major cause of hospital infection and transmits its antibiotic resistance through conjugation. This work aims to develop better understanding of the pheromone-induced plasmid transfer.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BST-T (02))
Program Officer
Lyster, Peter
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Minnesota Twin Cities
Engineering (All Types)
Schools of Engineering
United States
Zip Code
Breuer, Rebecca J; Bandyopadhyay, Arpan; O'Brien, Sofie A et al. (2017) Stochasticity in the enterococcal sex pheromone response revealed by quantitative analysis of transcription in single cells. PLoS Genet 13:e1006878
Chen, Yuqing; Bandyopadhyay, Arpan; Kozlowicz, Briana K et al. (2017) Mechanisms of peptide sex pheromone regulation of conjugation in Enterococcus faecalis. Microbiologyopen 6:
Bandyopadhyay, Arpan; O'Brien, Sofie; Frank, Kristi L et al. (2016) Antagonistic Donor Density Effect Conserved in Multiple Enterococcal Conjugative Plasmids. Appl Environ Microbiol 82:4537-45
Shu, Che-Chi; Tran, Vu; Binagia, Jeremy et al. (2015) On speeding up stochastic simulations by parallelization of random number generation. Chem Eng Sci 137:828-836
Otto, Lauren M; Mohr, Daniel A; Johnson, Timothy W et al. (2015) Polarization interferometry for real-time spectroscopic plasmonic sensing. Nanoscale 7:4226-33
Mishra, Neeraj K; Urick, Andrew K; Ember, Stuart W J et al. (2014) Fluorinated aromatic amino acids are sensitive 19F NMR probes for bromodomain-ligand interactions. ACS Chem Biol 9:2755-60
Kim, Yungil; Tsuda, Kenichi; Igarashi, Daisuke et al. (2014) Mechanisms underlying robustness and tunability in a plant immune signaling network. Cell Host Microbe 15:84-94
Bloch, Sarah E; Schmidt-Dannert, Claudia (2014) Construction of a chimeric biosynthetic pathway for the de novo biosynthesis of rosmarinic acid in Escherichia coli. Chembiochem 15:2393-401
Barik, Avijit; Otto, Lauren M; Yoo, Daehan et al. (2014) Dielectrophoresis-enhanced plasmonic sensing with gold nanohole arrays. Nano Lett 14:2006-12
Haugner 3rd, John C; Seelig, Burckhard (2013) Universal labeling of 5'-triphosphate RNAs by artificial RNA ligase enzyme with broad substrate specificity. Chem Commun (Camb) 49:7322-4

Showing the most recent 10 out of 35 publications