CadC Regulates cad and tdc Operons in Response to Gastrointestinal Stresses and Enhances Intestinal Colonization of Klebsiella pneumoniae

Background. To explore the mechanisms that enable Klebsiella pneumoniae to survive in the gastrointestinal tract, we characterized the roles of the cad and tdc operons during the bacterial response to acid and bile stress. Methods. The transcriptional units of the cad and tdc loci were identified by reverse-transcription polymerase chain reaction (RT-PCR). Transcriptional regulation of the cad and tdc operons under either acid or bile stress was analyzed by real-time RT-PCR. The ability of the mutant strains to colonize the gastrointestinal tract was examined through competition with the wild-type strain during intragastric infection of mice. Results. The cad and tdc operons were single transcriptional units. The NTUH-K2044 wild-type strain displayed an acid tolerance response to inorganic acid and was able to survive in bile encountered in vivo. Altered transcription of the cad and tdc operons by acid depended on CadC. Under either bile stress or acidic conditions, the transcriptional regulation of the tdc operon depended on TdcA. Both the cadCBA and the tdcABCDE mutant strains were impaired in their ability to colonize the mouse intestine, compared with that of the wild-type strain. Conclusion. These results suggest that the cad and tdc loci in K. pneumoniae are involved in the adaptation of the organism to gastrointestinal stress and intestinal colonization.