Mechanistic Features of the Enterococcal pCF10 Sex Pheromone Response and the Biology of Enterococcus faecalis in Its Natural Habitat

Abstract

Conjugative transfer of plasmids in enterococci is promoted by intercellular communication using peptide pheromones. The regulatory mechanisms that control transfer have been extensively studied However, the complicated systems that regulate the spread of these plasmids did not evolve in the laboratory test tube, and remarkably little is known about this form of signaling in the intestinal tract, the primary niche of these organisms. Because the evolution of strains and their coresident pheromone-inducible plasmids, such as pCF10, have occurred in the gastrointestinal (GI) tract, it is important to consider the functions controlled by pheromones in light of this ecology. This review summarizes our current understanding of the pCF10-encoded pheromone response. We consider how selective pressures in the natural environment may have selected for the complex and very tightly regulated systems controlling conjugation, and we pay special attention to the ecology of enterococci and the pCF10 plasmid as a gut commensal. We summarize the results of recent studies of the pheromone response at the single-cell level, as well as those of the first experiments demonstrating a role for pheromone signaling in plasmid transfer and in GI tract competitive fitness. These results will serve as a foundation for further studies that could lead to novel interventions to reduce opportunistic infections and the spread of antibiotic resistance.

Omadacycline Efficacy against Enterococcus faecalis Isolated in China: In Vitro Activity, Heteroresistance, and Resistance Mechanisms

“…through natural or acquired resistance mechanisms (4,5). Recently, several reports have shown that the increased incidence of multidrug-resistant enterococci, including vancomycin (VAN)-resistant and linezolid (LZD)-resistant strains, has limited our treatment choices, and controlling multidrug-resistant E. faecalis infections has become a critical need in clinics (4)(5)(6).…”

Direct cell–cell contact activates SigM to express the ESX-4 secretion system inMycobacterium smegmatis

“…Coordinated regulation of conjugal transfer genes is critical, as efficient conjugation systems must identify compatible partners and culminate with the stable maintenance of the transferred mobilized DNA in the resulting transconjugant (4). This coordination is exemplified by some conjugative systems that encode pheromones to regulate donor and recipient functions (5)(6)(7).…”

Competent but complex communication: The phenomena of pheromone-responsive plasmids

“…In all cases, animal models were inoculated with donor and recipient strains each at 10 7 colony-forming units (CFU) and above. Typical enterococcal numbers within humans range between 10 5 and 10 7 CFU per gram; thus, the abovementioned results reflect the transfer of PRP under conditions of dysbiosis [17][18][19][20][21].…”

“…The 5 0 region is regulatory and is followed by the adherence module, which mediates cell aggregation. The distal end of the operon encodes the plasmid mobilisation genes, consisting of a type 4 secretion system (T4SS) utilised as a bacterial mating channel between donor and recipient cells, in addition to plasmid processing genes [20].…”