aeruginosa. Cellular motility and biofilm formation are highly complex processes that need

precise regulation and many regulators have already been identified by different groups (Brinkman et al., 2001; Heurlier et al., 2004; Whitchurch et al., 2004; Leech & Mattick, 2006; Shrout et al., 2006; Kuchma et al., 2007; Merritt et al., 2007; Sakuragi & Kolter, 2007). Among them, the virulence-related two-component system PhoP/PhoQ plays an important role (Brinkman et al., 2001; McPhee et al., 2003, 2006; Gooderham & Hancock, 2009). We observed Alectinib chemical structure that the response regulator protein PhoP accumulated in the lipC mutant as revealed by proteome analysis. On the other hand, real-time PCR experiments did not show any differences between the expression levels of phoP genes in the wild type and lipC mutant strains (data not shown). The observed increase of PhoP in the lipC mutant may therefore be the result of a post-transcriptional process. Our proteome analysis additionally revealed the accumulation of protein PA3554. The corresponding gene is part of an operon and its homologue is involved in lipopolysaccharide modification in S. typhimurium (Noland et al., 2002). This gene has been shown to be regulated by PhoP in P. aeruginosa (McPhee et al., 2006), which is confirmed by our finding. Hancock and coworkers have shown previously that a PhoP

knockout mutation resulted in a hyperswarming phenotype in P. aeruginosa (Brinkman et al., 2001). MI-503 mouse This result coincides with our finding that a significant increase of PhoP in the lipC mutant resulted in a swarming deficiency. Inactivation of the cognate sensor kinase PhoQ, in contrast, resulted in defects in swarming and twitching, altered biofilm formation and significantly influenced virulence of P. aeruginosa (Gooderham et al., 2009). Moreover, in this PhoQ-negative background, expression

of the response regulator PhoP was induced considerably by a factor of about 80 (Gooderham et al., 2009). These phenotypes are in parallel with the phenotypes observed with the lipC mutant in several aspects. Interestingly, the expression of the lipase LipA was shown to be reduced in the phoQ mutant on the transcriptional level (Gooderham this website et al., 2009). Both lipases LipA and LipC require the action of the lipase-specific chaperone LipH to acquire proper folding and enzyme activity (Martinez et al., 1999; Rosenau & Jaeger, 2000). This foldase is encoded and coregulated in an operon with the lipA gene, and the presence of a second lipase has been suspected to indicate a specific role of this closely related enzyme (Rosenau et al., 2004). Thus, although this needs to be proven, an additional consequence of the phoQ inactivation may be a decrease in LipC production in this strain, which may explain the phenotypic similarities and suggest a role of LipC in mediating PhoQ-dependent signal transduction and regulation, which is in part independent of the cognate PhoP regulator (Gooderham et al., 2009).