In Salmonella Typhimurium, YiiD Modulates cAMP Levels in Lag Phase During Growth on Succinate

In Salmonella Typhimurium (S. Typhimurium), yiiD encodes a two-domain protein, with one domain having bona fide malonyl-ACP decarboxylase activity, and the other showing sequence similarity to Gcn5-type acetyltransferases (GNATs). Recent work on this enzyme was motivated by the essentiality of its decarboxylase domain to initiation of fatty acid biosynthesis in a strain devoid of β-ketoacyl-[acyl-carrier-protein, ACP] synthase III (FabH) activity. A function for the putative GNAT domain has not been established. We find that a ∆yiiD strain has an unconventional, slow-growth lag phenotype during growth on succinate that is only weakly dependent on YiiD decarboxylase activity, implicating the putative GNAT domain. The ∆yiiD mutation suppresses the effect of a ∆rpoS mutation that is known to shorten the lag phase during growth on succinate, suggesting the function of the YiiD protein may also be regulatory. Isolation of spontaneous suppressor mutations in a ∆yiiD strain revealed changes in the promoter of cpdA, the gene encoding cyclic-AMP phosphodiesterase. Exogenous addition of cAMP to the medium fully abrogated the ∆yiiD phenotype, and intracellular cAMP measurements revealed that the ∆yiiD strain fails to accumulate cAMP during lag phase, with levels about half of those measured in the wildtype strain. During the lag phase, the ∆yiiD strain was also measured to have increased expression of the adenylate cyclase gene, cyaA, implying that the mechanism altering cAMP levels occurs posttranscriptionally. We conclude YiiD function is necessary for early cAMP accumulation during transitions into some non-phosphotransferase system (non-PTS) growth conditions. We suggest changing the name of the YiiD protein to LcmM (for lipid and carbon metabolism modulator) to encapsulate its roles in S. Typhimurium physiology.