Involvement of the accessory gene regulator (agr) in expression of type 5 capsular polysaccharide by Staphylococcus aureus

Dassy, Bruno; Hogan, T.; Foster, Timothy J.; Fournier, Jean‐Michel

doi:10.1099/00221287-139-6-1301

Cited by 48 publications

(39 citation statements)

References 51 publications

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“…Although capsule production is very important in the survival of S. aureus during different phases of infection, very little is known about the mechanism that regulates the cap operon. Several global regulators have been shown to affect the production of the capsule, indicating that several environmental and host signals must be integrated to fine-tune this process (Luong et al, , 2003(Luong et al, , 2011Luong & Lee, 2006;Chen et al, 2007;Dassy et al, 1993;Gupta et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Several global regulators have been shown to control the production of the capsule, including agr, sarA, arl and mgrA, as well as others (Luong et al, , 2003(Luong et al, , 2011Luong & Lee, 2006;Chen et al, 2007;Dassy et al, 1993;Gupta et al, 2013). A detailed analysis of the cap operon promoter has revealed that it is highly regulated (Ouyang et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…The deletion of the msaABCR operon alters the expression of several global regulators, including sarA, agr and sigB, all of which have been shown to be indirectly involved in capsule production (Bischoff et al, 2004;Pané-Farré et al, 2006;Meier et al, 2007;Dassy et al, 1993;Sahukhal & Elasri, 2014). The regulatory mechanism for msaABCR has not yet been defined.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MsaB activates capsule production at the transcription level in Staphylococcus aureus

2016

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“…In S. aureus, type 5 capsule has been shown to be downregulated by agr, a global regulatory locus (Dassy et al, 1993). Both type 5 and 8 capsules have been shown to be affected by different growth conditions Dassy et al, 1991;Stringfellow et al, 1991;Mamo et al, 1987), suggesting that they are regulated.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional analysis of type 1 capsule genes in Staphylococcus aureus

Ouyang

Lee

1997

Molecular Microbiology

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SummarySerotype 1 capsule of Staphylococcus aureus plays an important role in staphylococcal infections. A 14.6 kb chromosomal DNA fragment containing 13 cap1 genes responsible for the synthesis of type 1 capsule in S. aureus strain M has been previously cloned and sequenced in our laboratory. These genes are closely linked and are transcribed in one orientation. To study the transcription of these genes, we employed genetic complementation using a set of plasmids with various deletions in the 14.6 kb region to complement mutants mapped in each of the 13 genes. We found that there were six transcriptional units. By Northern hybridization using the entire gene cluster as a probe, we identified a large 14 kb band and several smaller bands ranging from 0.3 to 6 kb. The 14 kb band was also identified by various individual gene probes, suggesting that all 13 genes are transcribed into a large transcript. The 14 kb transcript and the smaller bands were not detected when a 533 bp fragment containing the potential promoter region upstream of the first gene (cap1A) was deleted from the chromosome, suggesting that the small transcripts are the degradation (processing) products of the 14 kb transcript. The activities of the promoters identified by genetic complementation tests were quantitatively measured by transcriptional fusions using xylE as the reporter gene. The result showed that the promoter preceding the first cap1 gene was 45-198-fold higher than the downstream promoters. The result from gene-fusion studies is in agreement with the Northern analysis in that only the transcript transcribed from the first promoter was detected. Taken together, these results suggest that the cap1 genes are organized as a large operon with at least five weak internal promoters, and the long polycistronic transcript is processed (degraded) into several smaller transcripts. The transcription initiation site of the primary transcript was mapped by S1 nuclease mapping and the major promoter was defined by deletion analysis of the promoter-xylE fusion. In addition, we showed that the internal promoters, despite their weak activities, were sufficiently effective at expressing their downstream genes required for producing capsule, compared to the wild-type strain.

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“…One possible role of B in this scenario is to prolong the production of cell surface proteins, such as fibronectin binding proteins, that are positively influenced by SarA and negatively influenced by agr (55,60). Simultaneously, B may down-regulate RNAIII-specific activities, i.e., the repression of protein A and upregulation of exoproteins (36,49) or the production of capsular polysaccharides (22,51). Consistent with this hypothesis is our finding that the rsbU ϩ derivative GP268 possessed a significantly lower fibronectin-clumping titer than its rsbU-defective parent, BB255, signalling the presence of larger quantities of fibronectin binding proteins in GP268 than in BB255.…”

Section: Fig 8 Effect Of Overexpressedmentioning

confidence: 99%

Influence of a Functional sigB Operon on the Global Regulators sar and agr in Staphylococcus aureus

2001

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The growth phase-dependent activity profile of the alternate transcription factor B and its effects on the expression of sar and agr were examined in three different Staphylococcus aureus strains by Northern blot analyses and by the use of reporter gene fusion experiments. Significant B activity was detectable only in the clinical isolates MSSA1112 and Newman, carrying the wild-type rsbU allele, but not in the NCTC8325 derivative BB255, which is defective in rsbU.B activity peaked in the late exponential phase and diminished towards the stationary phase when bacteria were grown in Luria-Bertani medium. Transcriptional analysis and a sarP1-sarP2-sarP3 (sarP1-P2-P3)-driven firefly luciferase (luc؉) reporter gene fusion demonstrated a strong B activity-and growth phase-dependent increase in sar expression that was totally absent in either rsbU or ⌬rsbUVWsigB mutants. In contrast, expression of the agr locus, as measured by RNAIII levels and by an hldp::luc؉ fusion, was found to be higher in the absence of B activity, such as in rsbU or ⌬rsbUVWsigB mutants, than in wild-type strains. Overexpression of B in BB255 derivatives resulted in a clear increase in sarP1-P2-P3::luc؉ expression as well as a strong decrease in hldp::luc؉ expression. The data presented here suggest that B increases sar expression while simultaneously reducing the RNAIII level in a growth phasedependent manner.Staphylococcus aureus is a major human pathogen causing a variety of infections, ranging from minor skin and wound infections to life-threatening diseases (42). Pathogenicity in S. aureus is based on a wide range of cell wall-associated and extracellular proteins that are regulated in a coordinate and growth phase-dependent manner. These virulence determinants are controlled among others by the accessory gene regulator agr and the staphylococcal accessory regulator sar (48). Mutations in either agr or sar result in mutants that are strongly attenuated in virulence compared to their corresponding parental strains (1,8,15,31).The agr locus regulates the expression of cell wall-associated proteins and secreted exoproteins in response to the density of the bacterial population (37). The proposed function of this regulatory system is to enhance the production of wall-associated adhesins, which interact with the host's matrix proteins, and potential defense factors (protein A) in the early stages of infection. This is followed by the expression of excreted invasion factors, such as hemolysins, proteases, and lipases, that are suggested to be involved in the dissemination of the organism from the primary site of infection once the infection has been established (58). The agr locus comprises two divergent transcriptional units, RNAII and RNAIII, which are transcribed from the agrP2 and agrP3 promoters, respectively (Fig. 1B) (reviewed in reference 46). RNAII encodes a four-gene operon, including a two-component signal transduction system that responds to the concentration of a secreted and processed peptide pheromone, which is encoded within the op...

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Involvement of the accessory gene regulator (agr) in expression of type 5 capsular polysaccharide by Staphylococcus aureus

Cited by 48 publications

References 51 publications

MsaB activates capsule production at the transcription level in Staphylococcus aureus

MsaB activates capsule production at the transcription level in Staphylococcus aureus

Transcriptional analysis of type 1 capsule genes in Staphylococcus aureus

Influence of a Functional sigB Operon on the Global Regulators sar and agr in Staphylococcus aureus

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