The VraS/VraR two-component regulatory system required for oxacillin resistance in community-acquired methicillin-resistant<i>Staphylococcus aureus</i>

Boyle-Vavra, Susan; Yin, Shaohui; Daum, Robert S.

doi:10.1111/j.1574-6968.2006.00384.x

Cited by 96 publications

(95 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MIC/MBC assays conducted with non-lipid II interacting ␤-lactams (penicillin G and oxacillin) that prevent the later transpeptidation step of PG biosynthesis, as well as Dcycloserine, which competitively inhibits the completion of the PG subunit pentapeptide side chain, revealed no effect on the sensitivities of lia mutants relative to parent (Table 2) (10). Unlike S. mutans LiaSR, resistance to these antibiotics in S. aureus partly involves the homologous VraSR system (8,18,29). Indeed, oxacillin showed drastic (at most 64-fold) reduction in the MICs of a vraSR mutant compared to the parent methicillin-resistant S. aureus strain (8).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The LiaFSR System Regulates the Cell Envelope Stress Response inStreptococcus mutans

et al. 2009

View full text Add to dashboard Cite

Maintaining cell envelope integrity is critical for bacterial survival, including bacteria living in a complex and dynamic environment such as the human oral cavity. Streptococcus mutans, a major etiological agent of dental caries, uses two-component signal transduction systems (TCSTSs) to monitor and respond to various environmental stimuli. Previous studies have shown that the LiaSR TCSTS in S. mutans regulates virulence traits such as acid tolerance and biofilm formation. Although not examined in streptococci, homologs of LiaSR are widely disseminated in Firmicutes and function as part of the cell envelope stress response network. We describe here liaSR and its upstream liaF gene in the cell envelope stress tolerance of S. mutans strain UA159. Transcriptional analysis established liaSR as part of the pentacistronic liaFSR-ppiB-pnpB operon. A survey of cell envelope antimicrobials revealed that mutants deficient in one or all of the liaFSR genes were susceptible to Lipid II cycle interfering antibiotics and to chemicals that perturbed the cell membrane integrity. These compounds induced liaR transcription in a concentration-dependent manner. Notably, under bacitracin stress conditions, the LiaFSR signaling system was shown to induce transcription of several genes involved in membrane protein synthesis, peptidoglycan biosynthesis, envelope chaperone/proteases, and transcriptional regulators. In the absence of an inducer such as bacitracin, LiaF repressed LiaR-regulated expression, whereas supplementing cultures with bacitracin resulted in derepression of liaSR. While LiaF appears to be an integral component of the LiaSR signaling cascade, taken collectively, we report a novel role for LiaFSR in sensing cell envelope stress and preserving envelope integrity in S. mutans.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Unlike S. mutans LiaSR, resistance to these antibiotics in S. aureus partly involves the homologous VraSR system (8,18,29). Indeed, oxacillin showed drastic (at most 64-fold) reduction in the MICs of a vraSR mutant compared to the parent methicillin-resistant S. aureus strain (8).…”

Section: Resultsmentioning

confidence: 99%

The LiaFSR System Regulates the Cell Envelope Stress Response inStreptococcus mutans

et al. 2009

View full text Add to dashboard Cite

show abstract

“…A LiaRS homologue, the VraSR system of Staphylococcus aureus, has also been reported to contribute to antibiotic resistance in clinical isolates of Staph. aureus (Boyle-Vavra et al, 2006;Gardete et al, 2006;Kuroda et al, 2003Kuroda et al, , 2000. Other than the cell wall stress responses, LiaS (formerly designated HK11) has been found to play a role in acid resistance; it may act as a pH sensor (Li et al, 2002) and regulate virulence factor expression in Streptococcus mutans (Chong et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Analysis of two-component sensor proteins involved in the response to acid stimuli in Streptococcus pyogenes

et al. 2011

View full text Add to dashboard Cite

The virulence of Streptococcus pyogenes depends on proteins that are produced by this bacterium. The production of virulence proteins depends on environmental factors, and twocomponent regulatory systems are considered to be involved in sensing these factors. One of the environmental factors is acid stimuli. We established knockout strains in all speculated twocomponent regulatory sensor proteins of the M1 clinical strain of S. pyogenes and examined their relevance to acid stimuli. The parental strain and its derived knockout strains were cultured in a medium adjusted to pH 7.6 or 6.0, and their growth in broth was compared. The spy1622 sensor knockout strain showed significant growth reduction compared with the parental strain in broth at pH 6.0, suggesting that the Spy1622 two-component sensor protein is involved in sensing acid stimuli. To further examine the role of the Spy1622 two-component sensor protein in virulence, blood bactericidal assays and mouse infection model experiments were performed. We found that the spy1622 knockout strain was less virulent than the parental strain, which suggests that the Spy1622 two-component sensor protein could play an important role in virulence. INTRODUCTIONStreptococcus pyogenes is a Gram-positive bacterium that infects the upper respiratory tract, for example the tonsils and pharynx, and causes serious post-infectious diseases such as rheumatic fever and glomerulonephritis. Furthermore, S. pyogenes causes even more serious human diseases such as streptococcal toxic shock syndrome (STSS), whose mortality rate is considerable (Cone et al., 1987;Cunningham, 2000). Because of the worldwide prevalence of STSS, a number of studies have been undertaken to identify relevant virulence factors (Hauser et al., 1991;Reichardt et al., 1992). These factors include M protein, streptococcal inhibitor of complement, streptococcal pyrogenic toxins, haemolysins, and several DNases (Cunningham, 2000).The production of virulence proteins depends on environmental factors such as pH. Bacterial growth and the host environment, such as that in phagocytic cells, can cause local and temporal pH changes, and bacteria can subsequently sense the pH change as a signal to modify their growth mode. In addition, bacteria can modulate their gene expression in response to changes in pH (Loughman & Caparon, 2006). Hence, pH is considered to play an important role in host colonization and infection by S. pyogenes.The regulation of virulence protein expression in S. pyogenes is mainly controlled by stand-alone response regulators and two-component regulatory systems (TCSs). Stand-alone transcriptional regulators have no identified sensory domain (Kreikemeyer et al., 2003). The three characterized stand-alone regulators include Mga, Rgg and RofA-like family members (McIver et al., 1995;Beckert et al., 2001;Chaussee et al., 1999;Lyon et al., 1998;Molinari et al., 2001;Podbielski et al., 1999). A TCS consists of a sensor protein and a regulatory protein.Thirteen TCSs have been identified in the available S. ...

show abstract

“…Strain LAC⌬pvl was a gift from Michael Otto (National Institutes of Health, Bethesda, MD). Strain 923 is a highly virulent USA300 CA-MRSA strain isolated at the University of Chicago Medical Center from a patient with an abscess (3,23). Its virulence phenotype in rodent models of necrotizing pneumonia and skin infection has been described (23)(24)(25).…”

Section: Methodsmentioning

confidence: 99%

CodY Deletion Enhances In Vivo Virulence of Community-Associated Methicillin-Resistant Staphylococcus aureus Clone USA300

et al. 2012

Self Cite

View full text Add to dashboard Cite

ABSTRACTTheStaphylococcus aureusglobal regulator CodY responds to nutrient availability by controlling the expression of target genes.In vitro, CodY represses the transcription of virulence genes, but it is not known if CodY also represses virulencein vivo. The dominant community-associated methicillin-resistantS. aureus(CA-MRSA) clone, USA300, is hypervirulent and has increased transcription of global regulators and virulence genes; these features are reminiscent of a strain defective in CodY. Sequence analysis revealed, however, that thecodYgenes of USA300 and other sequencedS. aureusisolates are not significantly different from thecodYgenes in strains known to have active CodY.codYwas expressed in USA300, as well as in other pulsotypes assessed. Deletion ofcodYfrom a USA300 clinical isolate resulted in modestly increased expression of the global regulatorsagrandsaeRS, as well as the gene encoding the toxin alpha-hemolysin (hla). A substantial increase (>30-fold) in expression of thelukF-PVgene, encoding part of the Panton-Valentine leukocidin (PVL), was observed in thecodYmutant. All of these expression differences were reversed by complementation with a functionalcodYgene. Moreover, purified CodY protein bound upstream of thelukSF-PVoperon, indicating that CodY directly represses expression oflukSF-PV. Deletion ofcodYincreased the virulence of USA300 in necrotizing pneumonia and skin infection. Interestingly, deletion oflukSF-PVfrom thecodYmutant did not attenuate virulence, indicating that the hypervirulence of thecodYmutant was not explained by overexpression of PVL. These results demonstrate that CodY is active in USA300 and that CodY-mediated repression restrains the virulence of USA300.

show abstract

The VraS/VraR two-component regulatory system required for oxacillin resistance in community-acquired methicillin-resistantStaphylococcus aureus

Cited by 96 publications

References 31 publications

The LiaFSR System Regulates the Cell Envelope Stress Response inStreptococcus mutans

The LiaFSR System Regulates the Cell Envelope Stress Response inStreptococcus mutans

Analysis of two-component sensor proteins involved in the response to acid stimuli in Streptococcus pyogenes

CodY Deletion Enhances In Vivo Virulence of Community-Associated Methicillin-Resistant Staphylococcus aureus Clone USA300

Contact Info

Product

Resources

About