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The novel transcriptional regulator SczA mediates protection against Zn 2+ stress by activation of the Zn 2+ ‐resistance gene czcD in Streptococcus pneumoniae
Author(s) -
Kloosterman Tomas G.,
Van Der KooiPol Magdalena M.,
Bijlsma Jetta J. E.,
Kuipers Oscar P.
Publication year - 2007
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 - 10.1111/j.1365-2958.2007.05849.x
Subject(s) - tetr , biology , gene , mutant , regulator , regulation of gene expression , repressor , transcription (linguistics) , gene expression , microbiology and biotechnology , transcription factor , virulence , transcriptional regulation , genetics , linguistics , philosophy
Summary Maintenance of the intracellular homeostasis of metal ions is important for the virulence of many bacterial pathogens. Here, we demonstrate that the czcD gene of the human pathogen Streptococcus pneumoniae is involved in resistance against Zn 2+ , and that its transcription is induced by the transition‐metal ions Zn 2+ , Co 2+ and Ni 2+ . Upstream of czcD a gene was identified, encoding a novel TetR family regulator, SczA, that is responsible for the metal ion‐dependent activation of czcD expression. Transcriptome analyses revealed that in a sczA mutant expression of czcD , a gene encoding a MerR‐family transcriptional regulator and a gene encoding a zinc‐containing alcohol dehydrogenase ( adhB ) were downregulated. Activation of the czcD promoter by SczA is shown to proceed by Zn 2+ ‐dependent binding of SczA to a conserved DNA motif. In the absence of Zn 2+ , SczA binds to a second site in the czcD promoter, thereby fully blocking czcD expression. This is the first example of a metalloregulatory protein belonging to the TetR family that has been described. The presence in S. pneumoniae of the Zn 2+ ‐resistance system characterized in this study might reflect the need for adjustment to a fluctuating Zn 2+ pool encountered by this pathogen during infection of the human body.