REVIEW The DSF Family of Cell–Cell Signals: An Expanding Class of Bacterial Virulence Regulators

Many pathogenic bacteria use cell–cell signaling systems involving the synthesis and per-ception of diffusible signal molecules to control virulence as a response to cell density or confinement to niches. Bacteria produce signals of diverse structural classes. Signal mole-cules of the diffusible signal factor (DSF) family are cis-2-unsaturated fatty acids. The para-digm is cis-11-methyl-2-dodecenoic acid from Xanthomonas campestris pv. campestris (Xcc), which controls virulence in this plant pathogen. Although DSF synthesis was thought to be restricted to the xanthomonads, it is now known that structurally related molecules are produced by the unrelated bacteria Burkholderia cenocepacia and Pseudomonas aerugi-nosa. Furthermore, signaling involving these DSF family members contributes to bacterial virulence, formation of biofilms and antibiotic tolerance in these important human patho-gens. Here we review the recent advances in understanding DSF signaling and its regula-tory role in different bacteria. These advances include the description of the pathway/ mechanism of DSF biosynthesis, identification of novel DSF synthases and new members of the DSF family, the demonstration of a diversity of DSF sensors to include proteins with a Per-Arnt-Sim (PAS) domain and the description of some of the signal transduction mecha-nisms that impinge on virulence factor expression. In addition, we address the role of DSF family signals in interspecies signaling that modulates the behavior of other microorgan-isms. Finally, we consider a number of recently reported approaches for the control of bac-terial virulence through the modulation of DSF signaling