In a previous report (1978, Proc. Nat. Acad. Sci. USA 75, 3479-3483), we showed that recipient strains of Streptococcus faecalis excrete a heat-stable substance (sex pheromone) which induces donor cells carrying certain conjugative plasmids to become adherent, generating the cell-to-cell contact necessary for plasmid transfer. Since donors themselves could be induced to aggregate or "clump" by recipient filtrates, the substance was referred to as "clumping-inducing agent" (CIA). In this report, we present a simplified assay for CIA and determine the level of activity in filtrates prepared at various stages of growth. We also present evidence that recipient cells produce multiple pheromones, each specific for donors harboring a particular class of plasmids. Whereas a recipient that acquires a conjugative plasmid no longer produces the corresponding CIA, it still produces CIAs specific for donors with different conjugative plasmids. In addition, an analysis of 100 clinical isolates of S. faecalis showed that drug-resistant strains are significantly more likely to respond to and produce CIA activities than drug-sensitive strains. A model is discussed describing the relationships of sex pheromones to the mating process.
Bibliographical noteFunding Information:
We thank Paul Tomich, Yoshihiko Yagi, and Byron Brown for helpful discussionsa nd assistancei n certain aspects of this work; Karen Kalwaic of University Hospital (Ann Arbor) for providing us with the clinical isolates; and Charles Kowalski for assistancei n the statisticala nalyses.T his work was supportedb y Public Health Research Grant DE02731 from the National Institute of Dental Research and Grant K04 A100061 (Research Career DevelopmentA ward to DBC) from the National Institute of Allergy and Infectious Diseases.G .M.D. was supportedb y a National Science Foundation Graduate Fellowship and an F. G. Novy Fellowship from the Department of Microbiology, University of Michigan School of Medicine.