title: Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer.
abstract: Conjugation is one of the most common ways bacteria acquire antibiotic resistance, contributing to the emergence of multidrug-resistant "superbugs." Bacteria of the genus Enterococcus faecalis are highly antibiotic-resistant nosocomial pathogens that use the mechanism of conjugation to spread antibiotic resistance between resistance-bearing donor cells and resistance-deficient recipient cells. Here, we report a unique quorum sensing-based communication system that uses two antagonistic signaling molecules to regulate conjugative transfer of tetracycline-resistance plasmid pCF10 in E. faecalis. A "mate-sensing" peptide sex pheromone produced by recipient cells is detected by donor cells to induce conjugative genetic transfer. Using mathematical modeling and experimentation, we show that a second antagonistic "self-sensing" signaling peptide, previously known to suppress self-induction of donor cells, also serves as a classic quorum-sensing signal for donors that functions to reduce antibiotic-resistance transfer at high donor density. This unique form of quorum sensing may provide a means of limiting the spread of the plasmid and present opportunities to control antibiotic-resistance transfer through manipulation of intercellular signaling, with implications in the clinical setting.
authors.affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Anushree
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Laura C C
authors.initials: LC
authors.lastname: Cook
authors.forename: Che-Chi
authors.initials: CC
authors.lastname: Shu
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Manias
authors.forename: Doraiswami
authors.initials: D
authors.lastname: Ramkrishna
authors.forename: Gary M
authors.initials: GM
authors.lastname: Dunny
authors.forename: Wei-Shou
authors.initials: WS
authors.lastname: Hu
mesh_terms: D003227:Conjugation, Genetic / Q000502:physiology*; D024881:Drug Resistance, Bacterial / Q000235:genetics* / Q000502:physiology; D013293:Enterococcus faecalis / Q000235:genetics* / Q000502:physiology; D008954:Models, Biological; D010957:Plasmids / Q000235:genetics; D021382:Protein Sorting Signals / Q000235:genetics*; D053038:Quorum Sensing / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D012724:Sex Attractants / Q000378:metabolism; D013752:Tetracycline
chemical_list: D021382:Protein Sorting Signals; D012724:Sex Attractants; D013752:Tetracycline