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Impact of the catabolite control protein CcpA in "Staphylococcus aureus"


Seidl, K. Impact of the catabolite control protein CcpA in "Staphylococcus aureus". 2008, University of Zurich, Faculty of Science.

Abstract

The catabolite control protein CcpA is the main regulator of carbon catabolite repression and activation in low-GC Gram-positive bacteria. In the presence of glucose, CcpA regulates gene expression by binding to so-called catabolite responsive elements (cre) located upstream of, or within the promoter regions of the regulated genes. CcpA has been extensively studied in different bacteria, and was found to not only regulate metabolic genes but also to control virulence and antimicrobial resistance. In this study, we analysed the role of CcpA in the pathogen Staphylococcus aureus.
Transcriptome analyses showed that more than 150 genes in the exponential growth phase were regulated by glucose in a CcpA-dependent manner, and that even in the absence of
glucose, CcpA regulated more than 200 genes. Many of the regulated genes encode metabolic enzymes, suggesting that CcpA plays a similar role in S. aureus as it does in other
bacteria. However, we also found some aspects of the CcpA regulon, which were specific for S. aureus.
The S. aureus CcpA was also involved in the regulation of some important virulence factors.
Glucose-dependent repression of hla-, spa-, and tst-expression, coding for α-hemolysin, protein A, and toxic shock syndrome toxin, respectively, was dependent on CcpA. The presence of putative cre-sites in the promoter regions of these genes suggested that they were under direct control of CcpA. In contrast, the glucose-mediated and CcpA-dependent downregulation of the capsule genes (cap) was probably indirect. Deletion ccpA reduced the
transcription of RNAIII, which is the effector molecule of the agr operon and regulates the expression of many exoproteins and cell wall associated proteins. The deletion was also found to significantly reduce methicillin resistance and a ΔccpA mutant was significantly
more susceptible to teicoplanin.
Moreover, deletion of ccpA abolished the capacity to form a biofilm under static and flow conditions, and was linked to decreased expression of icaA, a gene responsible for the
expression of PIA, an important component of the S. aureus biofilm matrix. Repression of icaA was presumably achieved via the upregulation of the TCA cycle genes citB and citZ in
the ΔccpA mutant. Loss of biofilm formation in the mutant also correlated with decreased cidA transcription, recently reported to contribute to the production of extracellular DNA, which is a further component of the S. aureus biofilm matrix.
The finding that S. aureus virulence and carbohydrate utilization are directly linked through CcpA shows an important mechanism, by which this pathogen modulates virulence factor production in response to changes in its environment.

The catabolite control protein CcpA is the main regulator of carbon catabolite repression and activation in low-GC Gram-positive bacteria. In the presence of glucose, CcpA regulates gene expression by binding to so-called catabolite responsive elements (cre) located upstream of, or within the promoter regions of the regulated genes. CcpA has been extensively studied in different bacteria, and was found to not only regulate metabolic genes but also to control virulence and antimicrobial resistance. In this study, we analysed the role of CcpA in the pathogen Staphylococcus aureus.
Transcriptome analyses showed that more than 150 genes in the exponential growth phase were regulated by glucose in a CcpA-dependent manner, and that even in the absence of
glucose, CcpA regulated more than 200 genes. Many of the regulated genes encode metabolic enzymes, suggesting that CcpA plays a similar role in S. aureus as it does in other
bacteria. However, we also found some aspects of the CcpA regulon, which were specific for S. aureus.
The S. aureus CcpA was also involved in the regulation of some important virulence factors.
Glucose-dependent repression of hla-, spa-, and tst-expression, coding for α-hemolysin, protein A, and toxic shock syndrome toxin, respectively, was dependent on CcpA. The presence of putative cre-sites in the promoter regions of these genes suggested that they were under direct control of CcpA. In contrast, the glucose-mediated and CcpA-dependent downregulation of the capsule genes (cap) was probably indirect. Deletion ccpA reduced the
transcription of RNAIII, which is the effector molecule of the agr operon and regulates the expression of many exoproteins and cell wall associated proteins. The deletion was also found to significantly reduce methicillin resistance and a ΔccpA mutant was significantly
more susceptible to teicoplanin.
Moreover, deletion of ccpA abolished the capacity to form a biofilm under static and flow conditions, and was linked to decreased expression of icaA, a gene responsible for the
expression of PIA, an important component of the S. aureus biofilm matrix. Repression of icaA was presumably achieved via the upregulation of the TCA cycle genes citB and citZ in
the ΔccpA mutant. Loss of biofilm formation in the mutant also correlated with decreased cidA transcription, recently reported to contribute to the production of extracellular DNA, which is a further component of the S. aureus biofilm matrix.
The finding that S. aureus virulence and carbohydrate utilization are directly linked through CcpA shows an important mechanism, by which this pathogen modulates virulence factor production in response to changes in its environment.

Additional indexing

Item Type:Dissertation
Referees:Eberl L, Berger-Bächi B
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
07 Faculty of Science > Department of Plant and Microbial Biology
Dewey Decimal Classification:570 Life sciences; biology
580 Plants (Botany)
610 Medicine & health
Language:English
Date:2008
Deposited On:15 Feb 2009 16:02
Last Modified:05 Apr 2016 13:01
Number of Pages:137
Related URLs:http://opac.nebis.ch/F/?local_base=NEBIS&con_lng=GER&func=find-b&find_code=SYS&request=005691476

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