VraSR Two-Component Regulatory System and Its Role in Induction of
 pbp2
 and
 vraSR
 Expression by Cell Wall Antimicrobials in
 Staphylococcus aureus

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

doi:10.1128/aac.50.1.336-343.2006

Cited by 79 publications

(106 citation statements)

References 22 publications

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“…1A) and includes the genes encoding the LiaFSR system (spr0343/44), thereby verifying the positive autoregulatory feedback loop observed for the homologous systems in B. subtilis, L. lactis, S. aureus, and Streptococcus mutans (21,29,43,47). Induction of the liaFSR operon and its downstream genes by bacitracin has also recently been described for the S. pneumoniae strain D39 (28).…”

Section: Resultsmentioning

confidence: 96%

The Pneumococcal Cell Envelope Stress-Sensing System LiaFSR Is Activated by Murein Hydrolases and Lipid II-Interacting Antibiotics

et al. 2010

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In the Firmicutes, two-component regulatory systems of the LiaSR type sense and orchestrate the response to various agents that perturb cell envelope functions, in particular lipid II cycle inhibitors. In the current study, we found that the corresponding system in Streptococcus pneumoniae displays similar properties but, in addition, responds to cell envelope stress elicited by murein hydrolases. During competence for genetic transformation, pneumococci attack and lyse noncompetent siblings present in the same environment. This phenomenon, termed fratricide, increases the efficiency of horizontal gene transfer in vitro and is believed to stimulate gene exchange also under natural conditions. Lysis of noncompetent target cells is mediated by the putative murein hydrolase CbpD, the key effector of the fratricide mechanism, and the autolysins LytA and LytC. To avoid succumbing to their own lysins, competent attacker cells must possess a protective mechanism rendering them immune. The most important component of this mechanism is ComM, an integral membrane protein of unknown function that is expressed only in competent cells. Here, we show that a second layer of self-protection is provided by the pneumococcal LiaFSR system, which senses the damage inflicted to the cell wall by CbpD, LytA, and LytC. Two members of the LiaFSR regulon, spr0810 and PcpC (spr0351), were shown to contribute to the LiaFSR-coordinated protection against fratricide-induced self-lysis.

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Section: Resultsmentioning

confidence: 96%

The Pneumococcal Cell Envelope Stress-Sensing System LiaFSR Is Activated by Murein Hydrolases and Lipid II-Interacting Antibiotics

et al. 2010

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“…3b) (37). The existence of this potential cis element suggests positive autoregulation, as with other LiaSR homologs (24,37,70).…”

Section: Resultsmentioning

confidence: 97%

“…However, the nature of the envelope stress signal and the regulon genes controlled by this system diverges based on the organism. While liaRS homologs in both L. lactis (cesSR) and S. aureus (vraSR) are transcriptionally induced by lipid II cycle inhibitors, the latter S. aureus system is unique in responding to a wider array of cell envelope antibiotics including teicoplanin, ␤-lactams and D-cycloserine (29,37,70). Moreover, in B. subtilis, LiaR regulates the transcription of its own liaIHGFSR operon and another operon encoding a second TCSTS (24).…”

mentioning

confidence: 99%

The LiaFSR System Regulates the Cell Envelope Stress Response inStreptococcus mutans

et al. 2009

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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.

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“…Also of relevance here are the transcriptional profiles of VSSA and VISA strains exposed to vancomycin and other cell wall-active antibiotics (168,199,202,361,392) or when cell (92,330). These experimental conditions lead to a cell envelope stress response (148) and the upregulation of a "cell wall stimulon" that responds to abnormal cell wall synthesis (199,361).…”

Section: Molecular Mechanisms Of Resistancementioning

confidence: 99%

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

et al. 2010

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SUMMARY The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) over the past decade has provided a challenge to diagnostic microbiologists to detect these strains, clinicians treating patients with infections due to these strains, and researchers attempting to understand the resistance mechanisms. Recent data show that these strains have been detected globally and in many cases are associated with glycopeptide treatment failure; however, more rigorous clinical studies are required to clearly define the contribution of hVISA to glycopeptide treatment outcomes. It is now becoming clear that sequential point mutations in key global regulatory genes contribute to the hVISA and VISA phenotypes, which are associated predominately with cell wall thickening and restricted vancomycin access to its site of activity in the division septum; however, the phenotypic features of these strains can vary because the mutations leading to resistance can vary. Interestingly, changes in the staphylococcal surface and expression of agr are likely to impact host-pathogen interactions in hVISA and VISA infections. Given the subtleties of vancomycin susceptibility testing against S. aureus, it is imperative that diagnostic laboratories use well-standardized methods and have a framework for detecting reduced vancomycin susceptibility in S. aureus.

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VraSR Two-Component Regulatory System and Its Role in Induction of pbp2 and vraSR Expression by Cell Wall Antimicrobials in Staphylococcus aureus

Cited by 79 publications

References 22 publications

The Pneumococcal Cell Envelope Stress-Sensing System LiaFSR Is Activated by Murein Hydrolases and Lipid II-Interacting Antibiotics

The Pneumococcal Cell Envelope Stress-Sensing System LiaFSR Is Activated by Murein Hydrolases and Lipid II-Interacting Antibiotics

The LiaFSR System Regulates the Cell Envelope Stress Response inStreptococcus mutans

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

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