Complex function for SicA, a Salmonella enterica serovar Typhimurium type III secretion-associated chaperone

Salmonella enterica encodes a type III secretion system within a pathogenic ity island located at centisome 63 that is essential for virulence. All typ e III secretion systems require the function of a family of low-molecular-w eight proteins that aid the secretion process by acting as partitioning fac tors and/or secretion pilots, One such protein is SicA, which is encoded im mediately upstream of the type III secreted proteins SipB and SipC. We foun d that the absence of SicA results in the degradation of both SipB and SipC . Interestingly, in the absence of SipC, SipB was not only stable but also secreted at wild-type levels in a sicA mutant background, indicating that S icA is not required for SipB secretion. We also found that SicA is capable of binding both SipB and SipC. These results are consistent with a SicA rol e as a partitioning factor for SipB and SipC, thereby preventing their prem ature association and degradation. We also found that introduction of a sic A null mutation results in the lack of expression of SopE, another type III -secreted protein. Such an effect was shown to be transcriptional. Introduc tion of a loss-of-function sipC mutation into the sicA mutant background re scued sopE expression. These results indicate that the effect of sicA on so pE expression is indirect and most likely exerted through a regulatory fact or(s) partitioned by SicA from SipC. These studies therefore describe a sur prisingly complex function for the Salmonella enterica type III secretion-a ssociated chaperone SicA.