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Alternative sigma factors in Staphylococcus aureus

Applicant Bischoff Markus
Number 100234
Funding scheme Project funding (Div. I-III)
Research institution Institut für Medizinische Mikrobiologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Medical Microbiology
Start/End 01.05.2003 - 31.05.2007
Approved amount 191'090.00
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Keywords (5)

alternative sigma factors; Sigma B; Sigma H; regulation of virulence determinant production; antibiotic- and stress resistance

Lay Summary (English)

Lead
Lay summary
This project aimed at the identification and characterization of the two alternative transcription factors Sigma B and Sigma H of Staphylococcus aureus. While Sigma H was found to control a very small regulon, encompassing the genes SA1374 and SA1418 only, and appeared to be inactive under all in vitro conditions analyzed, Sigma B was found to control a large regulon of at least 251 genes/operons in response to environmental and growth phase-dependent stimuli (Bischoff et al., 2004). While the majority of genes/operons found to be controlled by Sigma B activity were positively influenced by this transcription factor, still a high number of genes were identified to be repressed in presence of Sigma B. Gene products found to be influenced by Sigma B were involved in all manner of cellular processes, including cell envelope biosynthesis and turnover, intermediary metabolism, and signalling pathways. In vivo studies confirmed Sigma B to be active during the course of infection (Senn et al., 2005), and suggested this transcription factor to have a transient enhancing effect on bacterial density in the early stages of infection that is lost during progression (Entenza et al., 2004). Transcriptional start point analyses allowed to deduce the consensus promoter (GttTaa-N12/15-gGGTAt) for Sigma B in S. aureus, and physical interaction studies of the gene products encoded by the Sigma B operon indicated the presence of a partner-switching mechanism in the Sigma B activation cascade similar to that of Bacillus subtilis. However, findings showing that overexpression of RsbU was sufficient to trigger an immediate and strong activation of Sigma B identified a relevant difference in the regulation of Sigma B activation between B. subtilis and S. aureus in the cascade upstream of RsbU (Senn et al., 2005). The lack of apparent Sigma B consensus sequences in the promoters of a significant number of genes found to be controlled by Sigma B indicated the alternative transcription factor to regulate these genes indirectly. A search for effector molecules that might modulate Sigma B control over Sigma B-dependent genes lacking an apparent Sigma B promoter identified the two putative regulator homologs YabJ and SpoVG. Inactivation of the yabJ-spoVG locus in S. aureus was found to affect capsule formation and the antibiotic resistance levels in methicillin-resistant S. aureus (MRSA) and glycopeptide intermediate-resistant S. aureus (GISA), phenomena that have been associated with Sigma B activity, suggesting that the effector molecules of this locus might indeed function as regulators acting downstream of Sigma B (Meier et al., 2007).
Direct link to Lay Summary Last update: 21.02.2013

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