Bacterial Pheromone for Sex and Abstinence

Abstract

Bacteria can transfer DNA through a process called conjugation, and the transfer of these extrachromasomal plasmid DNAs contributes to virulence and antibiotic resistance. Chandler et al. report that in Enterococcus faecalis , a mammalian pathogen, the same pheromone that stimulates donor bacteria to initiate conjugation with plasmid-free recipients is also produced by the donor bacteria and regulates the donor sensitivity to recipient-produced pheromone. The bacterial chromosome encodes the pheromone (cCF10), so both the donor and the recipient can produce this molecule. To prevent conjugation with other donor cells, the donor cells have two mechanisms for suppressing the response to the endogenously produced pheromone. The plasmid in the donor cells contains the prgQ operon, which encodes genes responsible for conjugation and genes responsible for inhibition of conjugation. One of the conjugation inhibitors is a secreted inhibitor protein, iCF10, which binds and sequesters secreted cCF10, and another is the membrane protein PrgY, which degrades or binds cCF10 as it is released. Using mutant bacterial strains that lacked functional cCF10, Chandler et al. show that cCF10 produced by the donor cells stimulates the production of iCF10. Donor cells grown in human plasma or in vivo produce the plasmid-encoded aggregation factor Asc10, which contributes to cellular invasion and virulence of the bacteria. The mutant bacteria that did not produce functional cCF10 did not aggregate when exposed to plasma. Albumin was identified by iCF10 affinity chromatography as the protein that bound to iCF10, thereby shifting the balance between iCF10 and cCF10, allowing self-induction of the conjugation genes, including the one encoding the aggregation factor Asc10. Donor bacteria use self-produced cCF10 to set the sensitivity to recipient-produced cCF10 through an autocrine signaling pathway from cCF10 to iCF10. When only self-produced cCF10 is present, the majority is inactivated, and that which is not stimulates iCF10 production. Under conditions where iCF10 abundance is decreased or cCF10 is secreted in abundance by recipient cells, the iCF10 to cCF10 ratio is decreased and conjugation is initiated. J. R. Chandler, J. Hirt, G. M. Dunny, A paracrine peptide sex pheromone also acts as an autocrine signal to induce plasmid transfer and virulence factor expression in vivo . Proc. Natl. Acad. Sci. U.S.A. 102 , 15617-15622 (2005). [Abstract] [Full Text]