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A new level in the Vibrio cholerae ToxR virulence cascade: AphA is required for transcriptional activation of the tcpPH operon
Author(s) -
Skorupski Karen,
Taylor Ronald K.
Publication year - 1999
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.1999.01215.x
Subject(s) - operon , vibrio cholerae , virulence , biology , pilus , cholera toxin , plasmid , regulon , mutant , transcription (linguistics) , promoter , gene , transcription factor , pathogenicity island , microbiology and biotechnology , regulation of gene expression , activator (genetics) , gene expression , genetics , bacteria , linguistics , philosophy
The expression of the ToxR virulence regulon is dependent upon the regulatory proteins ToxR/ToxS, TcpP/TcpH and ToxT. We describe here a previously unidentified gene in Vibrio cholerae , aphA (activator of tcpP and tcpH expression), which is required for the transcription of the tcpPH operon. Under conditions normally optimal for virulence gene expression, an in frame aphA deletion decreased the expression of a cholera toxin promoter fusion ( ctx–lacZ ) and prevented the production of the toxin co‐regulated pilus (TCP). Plasmids producing ToxT or TcpP/H, but not ToxR, restored ctx–lacZ expression and TCP production in the ΔaphA strain, suggesting that the mutation interferes with toxT expression by influencing the transcription of tcpPH . Indeed, the expression of a chromosomal tcpP–lacZ fusion was reduced in the ΔaphA mutant and increased in both V. cholerae and Escherichia coli by introducing aphA expressed from an inducible promoter. These results support a model in which AphA functions at a previously unknown step in the ToxR virulence cascade to activate the transcription of tcpPH . TcpP/TcpH, together with ToxR/ToxS, then activate the expression of toxT resulting ultimately in the production of virulence factors such as cholera toxin and TCP.