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Cyclic AMP receptor protein is a repressor of adenylyl cyclase gene cyaA in Yersinia pestis.

Yersinia pestis is one of the most dangerous pathogens. The cyclic AMP receptor protein (CRP) is required for the full virulence of Y. pestis, and it acts as a transcriptional regulator to control a large regulon, which includes several virulence-associated genes. The regulatory action of CRP is triggered only by binding to the small molecule cofactor cyclic AMP (cAMP). cAMP is synthesized from adenosine triphosphate by the adenylyl cyclase encoded by cyaA. In the present work, the regulation of crp and cyaA by CRP was investigated by primer extension, LacZ fusion, electrophoretic mobility shift assay, and DNase I footprinting. No transcriptional regulatory association between CRP and its own gene could be detected under the growth conditions tested. In contrast, CRP bound to a DNA site overlapping the core promoter -10 region of cyaA to repress the cyaA transcription. The determination of cellular cAMP levels further verified that CRP negatively controlled cAMP production. Repression of cAMP production by CRP through acting on the cAMP synthesase gene cyaA would represent a mechanism of negative automodulation of cellular CRP function.