| Summary: | <p>Abstract</p> <p>Background</p> <p>Bacteria integrate numerous environmental stimuli when generating cellular responses. Increasing numbers of examples describe how one two-component system (TCS) responds to signals detected by the sensor of another TCS. However, the molecular mechanisms underlying this phenomenon remain poorly defined.</p> <p>Results</p> <p>Here, we report a connector-like factor that affects the activity of the CpxR/CpxA two-component system in <it>Salmonella enterica</it> serovar Typhimurium. We isolated a clone that induced the expression of a <it>cpxP-lac</it> gene fusion from a high-copy-number plasmid pool of random <it>Salmonella</it> genomic fragments. A 63-amino acid protein, CacA, was responsible for the CpxA/CpxR-dependent activation of the <it>cpxP</it> gene. The CpxR-activated genes <it>cpxP</it> and <it>spy</it> exhibited approximately 30% and 50% reductions in transcription, respectively, in a clean <it>cacA</it> deletion mutant strain in comparison to wild-type. From 33 response regulator (RR) deletion mutants, we identified that the RssB regulator represses <it>cacA</it> transcription. Substitution mutations in a conserved -10 region harboring the RNA polymerase recognition sequence, which is well conserved with a known RpoS -10 region consensus sequence, rendered the <it>cacA</it> promoter RpoS-independent. The CacA-mediated induction of <it>cpxP</it> transcription was affected in a <it>trxA</it> deletion mutant, which encodes thioredoxin 1, suggesting a role for cysteine thiol-disulfide exchange(s) in CacA-dependent Cpx activation.</p> <p>Conclusions</p> <p>We identified CacA as an activator of the CpxR/CpxA system in the plasmid clone. We propose that CacA may integrate the regulatory status of RssB/RpoS into the CpxR/CpxA system. Future investigations are necessary to thoroughly elucidate how CacA activates the CpxR/CpxA system.</p>
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