Studies on the Expression of Regulatory Locus sae in Staphylococcus aureus

Giraudo, Ana T.; Mansilla, María C.; Chan, Ana; Raspanti, Claudia; Nagel, Rosa

doi:10.1007/s00284-002-3853-z

Cited by 48 publications

(46 citation statements)

References 20 publications

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“…SigB may act indirectly on sae expression due to SigB-dependent inhibition of the agr system (20). The agr-dependent P1 activation is consistent with previous results from others (12,33) emphasizing that within the regulatory cascade of virulence gene regulation, the sae system is placed as a central downstream regulator.…”

Section: Vol 190 2008supporting

confidence: 78%

The Virulence Regulator Sae ofStaphylococcus aureus:Promoter Activities and Response to Phagocytosis-Related Signals

et al. 2008

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The two-component system SaeRS of Staphylococcus aureus is closely involved in the regulation of major virulence factors. However, little is known about the signals leading to saeRS activation. A total of four overlapping transcripts (T1 to T4) from three different transcription starting points are expressed in the sae operon. We used a ␤-galactosidase reporter assay to characterize the putative promoter regions within the saeRS upstream region. The main transcript T2 is probably generated by endoribonucleolytic processing of the T1 transcript. Only two distinct promoter elements (P1 and P3) could be detected within the saeRS upstream region. The P3 promoter, upstream of saeRS, generates the T3 transcript, includes a cis-acting enhancer element and is repressed by saeRS. The most distal P1 promoter is strongly autoregulated, activated by agr, and repressed by sigma factor B. In strain Newman a mutation within the histidine kinase SaeS leads to a constitutively activated sae system. Evaluation of different external signals revealed that the P1 promoter in strain ISP479R and strain UAMS-1 is inhibited by low pH and high NaCl concentrations but activated by hydrogen peroxide. The most prominent induction of P1 was observed at subinhibitory concentrations of ␣-defensins in various S. aureus strains, with the exception of strain ISP479R and strain COL. P1 was not activated by the antimicrobial peptides LL37 and daptomycin. In summary, the results indicate that the sensor molecule SaeS is activated by alteration within the membrane allowing the pathogen to react to phagocytosis related effector molecules.Staphylococcus aureus asymptomatically colonizes the noses of healthy individuals but also causes a variety of infections in humans. Polymorphonuclear neutrophils (PMNs) provide an effective line of defense against infections. However, S. aureus has developed a variety of mechanisms to avoid being killed by PMNs, including the expression of a number of immune modulators and toxins (for a review, see reference 8). The expression of most virulence and adherence factors is directly or indirectly influenced by diverse regulators such as agr, the alternative sigma factor B (SigB), sarA homologues or sae (for reviews, see references 4, 6, 17, and 32). Within this network sae appears to be a central downstream regulator that controls the expression of major virulence genes such as hla (coding for alpha-hemolysin), coa (coding for coagulase), or fnbA (coding for fibronectin-binding protein A) (11,33,39). Microarray analysis and proteomics have revealed that most of the genes activated by sae are involved in bacterial adhesion, immune modulation, or toxicity (25,29,38). In addition, the importance of gene regulation by sae in vivo was shown in several animal models (3,15,16,29,43).The sae locus consists of four open reading frames, two of which (saeR and saeS) show strong sequence homology to response regulators and to histidine kinases (HKs) of bacterial two-component regulators (10). Two additional open reading frames, saeP ...

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Section: Vol 190 2008supporting

confidence: 78%

The Virulence Regulator Sae ofStaphylococcus aureus:Promoter Activities and Response to Phagocytosis-Related Signals

et al. 2008

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“…For example, it has been reported that expression of the saeRS locus is activated by agr (Giraudo et al, 2003;Novick & Jiang, 2003). However, we did not observe a significant difference between the levels of saeRS expression between UAMS-1 and its agr mutant (Table 4).…”

Section: Transcriptional Profiling Of the Uams-1 Agr Reguloncontrasting

confidence: 49%

Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390

Cassat

Dunman

Murphy³

et al. 2006

Microbiology

147

157

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The production of Staphylococcus aureus virulence factors is under the control of complex regulatory circuits. Most studies aimed at defining these regulatory networks have focused on derivatives of the strain NCTC 8325, most notably RN6390. However, all NCTC 8325 derivatives, including RN6390, possess an 11 bp deletion in rsbU. This deletion renders NCTC 8325 derivatives naturally sigma-factor-B deficient. Recent studies have shown that RN6390 is also deficient, in comparison to clinical isolates, with respect to biofilm formation, a process which is important for both pathogenesis and antimicrobial resistance. Based on these considerations, the authors carried out genome-scale transcriptional profiling, comparing RN6390 with the virulent rsbU-positive clinical isolate UAMS-1. The results revealed significant genome-wide differences in expression patterns between RN6390 and UAMS-1, and suggested that the overall transcriptional profile of UAMS-1 is geared toward expression of factors that promote colonization and biofilm formation. In contrast, the transcriptional profile of RN6390 was heavily influenced by RNAIII expression, resulting in a phenotype characterized by increased production of exoproteins, and decreased capacity to form a biofilm. The greater influence of agr in RN6390 relative to UAMS-1 was also evident when the transcriptional profile of UAMS-1 was compared with that of its isogenic sarA and agr mutants. Specifically, the results indicate that, in contrast to NCTC 8325 derivatives, agr plays a limited role in overall regulation of gene expression in UAMS-1, when compared with sarA. Furthermore, by defining the sarA regulon in a biofilm-positive clinical isolate, and comparing the results with transcriptional profiling experiments defining biofilm-associated gene expression patterns in the same strain, the authors identified a sarA-regulated operon (alsSD) that is also induced in biofilms, and demonstrated that mutation of alsSD results in reduced capacity to form a biofilm.

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“…Evidence to support this hypothesis comes from the observation that L. reuteri RC-14 repressed the two-component signal-transduction system saeRS independently of agr. The saeRS system has been suggested to regulate the expression of many virulence factors downstream of agr, and to coordinate the agr quorum-sensing-dependent regulation with the effects of environmental signals (35)(36)(37). It has also been previously demonstrated in S. aureus Newman that saeRS is involved in the regulation of SSL11 expression (38), and that L. reuteri RC-14 inhibited SSL11 synthesis independently of the agr system (17).…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus reuteri -produced cyclic dipeptides quench agr -mediated expression of toxic shock syndrome toxin-1 in staphylococci

Wang²,

Xu³

et al. 2011

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

195

144

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The production of the staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) by Staphylococcus aureus has been associated with essentially all cases of menstruation-associated toxic shock syndrome (TSS). In this work, we show that the human vaginal isolate Lactobacillus reuteri RC-14 produces small signaling molecules that are able to interfere with the staphylococcal quorum-sensing system agr, a key regulator of virulence genes, and repress the expression of TSST-1 in S. aureus MN8, a prototype of menstrual TSS S. aureus strains. Quantitative real-time PCR data showed that transcription from the Ptst promoter, as well as the P2 and P3 promoters of the agr system from all four agr subgroups of S. aureus, was strongly inhibited in response to growth with L. reuteri RC-14 cultural supernatant. Alterations in the transcriptional levels of two other virulence-associated regulators sarA and saeRS were also observed, indicating a potential overall influence of L. reuteri RC-14 signals on the production of virulence factors in S. aureus. S. aureus promoter-lux reporter strains were used to screen biochemically fractionated L. reuteri RC-14 supernatant, and the cyclic dipeptides cyclo(L-Phe-L-Pro) and cyclo(L-Tyr-L-Pro) were identified as the signaling molecules. The results from this work contribute to a better understanding of interspecies cell-to-cell communication between Lactobacillus and Staphylococcus, and provide a unique mechanism by which endogenous or probiotic strains may attenuate virulence factor production by bacterial pathogens.diketopiperazine | two-component systems

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Studies on the Expression of Regulatory Locus sae in Staphylococcus aureus

Cited by 48 publications

References 20 publications

The Virulence Regulator Sae ofStaphylococcus aureus:Promoter Activities and Response to Phagocytosis-Related Signals

The Virulence Regulator Sae ofStaphylococcus aureus:Promoter Activities and Response to Phagocytosis-Related Signals

Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390

Lactobacillus reuteri -produced cyclic dipeptides quench agr -mediated expression of toxic shock syndrome toxin-1 in staphylococci

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