cholerae are induced in response to purified CAI-1 and AI-2, and also by autoinducers derived from other Vibrios co-cultured with V. cholerae within a mixed-species biofilm. These results suggest that autoinducer communication within a consortium may promote DNA exchange among Vibrios, perhaps contributing to the evolution of these bacterial pathogens. Vibrio cholerae, a common marine bacterium and the causative agent of the disease cholera, produces and then responds to extracellular small molecules called autoinducers

(AIs) to collectively control gene expression and coordinate group behaviors, a process called quorum sensing (QS) (Fuqua et al., 1994; Ng & Bassler, Osimertinib mw 2009). Specifically, V. cholerae produces two autoinducers: CAI-I (the product of the CqsA synthase), which is restricted to Vibrios,

and AI-2 (the product of the LuxS synthase), an interspecies autoinducer molecule produced by many bacteria (Chen et al., 2002; Xavier & Bassler, 2005; Higgins et al., 2007). At low cell density (low autoinducer levels) the phosphorylated response regulator LuxO activates transcription of multiple small RNAs that base-pair with and alter translation of several mRNAs, most notably repressing the translation find protocol of hapR, which encodes the master regulator of QS (Lenz et al., 2004; Hammer & Bassler, 2007; Svenningsen et al., 2009; Rutherford et al., 2011). At high cell density (high autoinducer levels), the binding of autoinducers to their cognate

receptors results in dephosphorylation and inactivation of LuxO, leading to the production of HapR. HapR represses multiple genes, and also activates others, such as the gene coding for ComEA, a ssDNA-binding protein required for DNA uptake or horizontal gene transfer (HGT) (Meibom et al., 2005) (Fig. 1). Thus, wild-type (WT) V. cholerae strains are naturally competent at high cell density, a ΔhapR mutant does not take up DNA, and a ΔluxO strain that constitutively expresses HapR is capable of comEA-dependent DNA uptake even at low cell density (Meibom et al., 2005; Blokesch & Schoolnik, 2008). A V. cholerae-like QS pathway is well conserved in other Vibrio species, such as Vibrio harveyi, which also produces both CAI-1 and AI-2 (Hammer & Bassler, 2008). Vibrios commonly form biofilms in marine environments Methocarbamol on abiotic and biotic surfaces and it was recently shown that QS-dependent DNA uptake by V. cholerae requires the presence of chitin, such as found in copepods molts and crab shells (Kaneko & Colwell, 1975; Huq et al., 1983; Meibom et al., 2005). A chitin-responsive pathway induces transcription of several genes including tfoX that encodes an additional regulator required along with HapR for positive control of comEA transcription (Kulshina et al., 2009; Smith et al., 2009; Yamamoto et al., 2010) (Fig. 1). Vibrio species can often be found together in marine settings (Kaneko & Colwell, 1975; Kaper et al., 1979; Sochard et al.