Regulation of virulence determinants in<i>Staphylococcus aureus</i>: complexity and applications

Bronner, Stéphane; Monteil, H.; Prévost, Gilles

doi:10.1016/j.femsre.2003.09.003

Cited by 372 publications

(370 citation statements)

References 115 publications

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“…The expression of virulence genes in S. aureus is controlled by very complicated regulatory circuitry (Bronner et al, 2004;Cheung et al, 2004;Novick, 2003) in which various regulators form a complex network to coordinately regulate different virulence genes. With regard to capsule, we have previously shown that both agr and mgr positively regulate capsule production mostly at the transcriptional level, whereas sarA does not play a role in transcriptional regulation but may have a minor effect at the post-translational level (Luong et al, , 2003.…”

Section: Discussionmentioning

confidence: 99%

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The arl locus positively regulates Staphylococcus aureus type 5 capsule via an mgrA-dependent pathway

Luong

Lee

2006

Microbiology

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Most clinical Staphylococcus aureus strains produce either type 5 or type 8 capsular polysaccharides. The production of these capsules is influenced by various environmental factors. To study the regulation of capsule, Tn551 transposon mutagenesis and transcriptional reporter gene fusion were employed to identify several putative regulatory loci that influenced capsule gene expression. One of these, the arl locus, was chosen for further analysis. Tn551 was found to insert within the coding region (near the translational start site of the arlR gene). ArlR, along with ArlS, forms a two-component system that has been previously shown to affect autolysis and production of several secreted proteins. Phenotypic analyses of the arlR-specific mutant and gene fusion analyses showed that arlR activated capsule production at the transcriptional level. However, gel mobility shift assays did not support activation of the capsule genes by direct ArlR binding to the primary cap5 promoter region upstream of the operon. In contrast, it was found that arl activated mgrA, an activator for capsule production, whereas mgrA did not have a significant effect on arlR. Genetic studies supported the notion that arlR functions upstream of mgrA with respect to the regulation of capsule production, although gene fusion studies indicated that arl could also regulate capsule independently from mgrA. Collectively, the results suggest that arl positively regulates capsule production at the transcriptional level primarily through an mgrA-dependent pathway.

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Section: Discussionmentioning

confidence: 99%

“…These regulators appear to form a complex network of regulation to coordinately control the virulence gene expression (for reviews see Bronner et al, 2004;Cheung et al, 2004;Novick, 2003). Previously, we showed that agr had a significant effect on capsule production .…”

Section: Introductionmentioning

confidence: 99%

The arl locus positively regulates Staphylococcus aureus type 5 capsule via an mgrA-dependent pathway

Luong

Lee

2006

Microbiology

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“…The ability of this pathogen to cause such infections relies on its many virulence factors and their coordinated regulation (David & Daum, 2010;Lowy, 1998;Cheung et al, 2004;Bronner et al, 2004;Somerville & Proctor, 2009;Novick & Geisinger, 2008). One of the major virulence factors is the capsular polysaccharide (CP) (O'Riordan & Lee, 2004).…”

Section: Introductionmentioning

confidence: 99%

MsaB activates capsule production at the transcription level in Staphylococcus aureus

2016

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Staphylococcus aureus produces several virulence factors that allow it to cause a variety of infections. One of the major virulence factors is the capsule, which contributes to the survival of the pathogen within the host as a way to escape phagocytosis. The production of the capsular polysaccharide is encoded in a 16 gene operon, which is regulated in response to several environmental stimuli including nutrient availability. For instance, the capsule is produced in the late-and post-exponential growth phases, but not in the early-or mid-exponential growth phase. Several regulators are involved in capsule production, but the regulation of the cap operon is still poorly understood. In this study, we show that MsaB activates the cap operon by binding directly to a 10 bp repeat in the promoter region. We show that despite the fact that MsaB is expressed throughout four growth phases, it only activates capsule production in the late-and post-exponential growth phases. Furthermore, we find that MsaB does not bind to its target site in the early and mid-exponential growth phases. This correlates with decreased nutrient availability and capsule production. These data suggest either that MsaB binding ability changes in response to nutrients or that other cap operon regulators interfere with the binding of MsaB to its target site. This study increases our understanding of the regulation of capsule production and the mechanism of action of MsaB.

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“…The highly adaptable nature of S. aureus, including the rapid development of antibiotic resistance and large tissue tropism, has resulted in it being one of the leading causes of infection in the United States (2). This versatility is made possible by the large array of virulence factors encoded in the S. aureus genome and on mobile genetic elements that are regulated by a complex, interactive network of regulatory systems including two-component signal transduction systems (TCSs) (3)(4)(5).…”

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confidence: 99%

Differential regulation of staphylococcal virulence by the sensor kinase SaeS in response to neutrophil-derived stimuli

Flack

Zurek

Meishery

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Two-component systems (TCSs) are highly conserved across bacteria and are used to rapidly sense and respond to changing environmental conditions. The human pathogen Staphylococcus aureus uses the S. aureus exoprotein expression (sae) TCS to sense host signals and activate transcription of virulence factors essential to pathogenesis. Despite its importance, the mechanism by which the histidine kinase SaeS recognizes specific host stimuli is unknown. After mutagenizing the predicted extracellular loop of SaeS, we discovered one methionine residue (M31) was essential for the ability of S. aureus to transcribe sae target genes, including hla, lukAB/lukGH, and hlgA. This single M31A mutation also significantly reduced cytotoxicity in human neutrophils to levels observed in cells following interaction with ΔsaeS. Another important discovery was that mutation of two aromatic anchor residues (W32A and F33A) disrupted the normal basal signaling of SaeS in the absence of inducing signals, yet both mutant kinases had appropriate activation of effector genes following exposure to neutrophils. Although the transcriptional profile of aromatic mutation W32A was consistent with that of WT in response to human α-defensin 1, mutant kinase F33A did not properly transcribe the γ-toxin genes in response to this stimulus. Taken together, our results provide molecular evidence for how SaeS recognizes host signals and triggers activation of select virulence factors to facilitate evasion of innate immunity. These findings have important implications for signal transduction in prokaryotes and eukaryotes due to conservation of aromatic anchor residues across both of these domains and the important role they play in sensor protein structure and function.host-pathogen interactions | membrane proteins

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Regulation of virulence determinants inStaphylococcus aureus: complexity and applications

Cited by 372 publications

References 115 publications

The arl locus positively regulates Staphylococcus aureus type 5 capsule via an mgrA-dependent pathway

The arl locus positively regulates Staphylococcus aureus type 5 capsule via an mgrA-dependent pathway

MsaB activates capsule production at the transcription level in Staphylococcus aureus

Differential regulation of staphylococcal virulence by the sensor kinase SaeS in response to neutrophil-derived stimuli

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