title: Autoregulation of PhoP/PhoQ and positive regulation of the cyclic AMP receptor protein-cyclic AMP complex by PhoP in Yersinia pestis.
abstract: Yersinia pestis is one of the most dangerous bacterial pathogens. PhoP and cyclic AMP receptor protein (CRP) are global regulators of Y. pestis, and they control two distinct regulons that contain multiple virulence-related genes. The PhoP regulator and its cognate sensor PhoQ constitute a two-component regulatory system. The regulatory activity of CRP is triggered only by binding to its cofactor cAMP, which is synthesized from ATP by adenylyl cyclase (encoded by cyaA). However, the association between the two regulatory systems PhoP/PhoQ and CRP-cAMP is still not understood for Y. pestis. In the present work, the four consecutive genes YPO1635, phoP, phoQ, and YPO1632 were found to constitute an operon, YPO1635-phoPQ-YPO1632, transcribed as a single primary RNA, whereas the last three genes comprised another operon, phoPQ-YPO1632, transcribed with two adjacent transcriptional starts. Through direct PhoP-target promoter association, the transcription of these two operons was stimulated and repressed by PhoP, respectively; thus, both positive autoregulation and negative autoregulation of PhoP/PhoQ were detected. In addition, PhoP acted as a direct transcriptional activator of crp and cyaA. The translational/transcriptional start sites, promoter -10 and -35 elements, PhoP sites, and PhoP box-like sequences were determined for these PhoP-dependent genes, providing a map of the PhoP-target promoter interaction. The CRP and PhoP regulons have evolved to merge into a single regulatory cascade in Y. pestis because of the direct regulatory association between PhoP/PhoQ and CRP-cAMP.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Yiquan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Yanping
authors.initials: Y
authors.lastname: Han
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Yan
authors.forename: Yafang
authors.initials: Y
authors.lastname: Tan
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Yujun
authors.initials: Y
authors.lastname: Cui
authors.forename: Zongmin
authors.initials: Z
authors.lastname: Du
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Wang
authors.forename: Yujing
authors.initials: Y
authors.lastname: Bi
authors.forename: Huiying
authors.initials: H
authors.lastname: Yang
authors.forename: Yajun
authors.initials: Y
authors.lastname: Song
authors.forename: Pingping
authors.initials: P
authors.lastname: Zhang
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhou
authors.forename: Ruifu
authors.initials: R
authors.lastname: Yang
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D002373:Cyclic AMP Receptor Protein / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D009876:Operon; D011401:Promoter Regions, Genetic; D018085:Regulon; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism; D015010:Yersinia pestis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002373:Cyclic AMP Receptor Protein; C079792:PhoQ protein, Bacteria; D037521:Virulence Factors; C061064:PhoP protein, Bacteria; D000242:Cyclic AMP; D000262:Adenylyl Cyclases