Structure of the Cell Wall of Staphylococcus aureus, Strain Copenhagen. VII. Mode of Action of the Bacteriolytic Peptidase from Myxobacter and the Isolation of Intact Cell Wall Polysaccharides*

Biochemistry ◽  
1967 ◽  
Vol 6 (3) ◽  
pp. 906-920 ◽  
Author(s):  
Donald J. Tipper ◽  
Jack L. Strominger ◽  
Jerald C. Ensign
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Mode Of Action ◽  
Intact Cell ◽  
Aureus Strain ◽  
Cell Wall Polysaccharides

Mode of action of the alpha toxin of Staphylococcus aureus

1970 ◽  
Vol 16 (1) ◽  
pp. 47-50 ◽  
Author(s):  
G. M. Wiseman ◽  
J. D. Caird
Keyword(s):  
Staphylococcus Aureus ◽  
Proteolytic Activity ◽  
Mode Of Action ◽  
Differential Sensitivity ◽  
Aureus Strain ◽  
Red Cell ◽  
Alpha Toxin ◽  
Reaction Products ◽  
Phenol Reagent

Rabbit erythrocytes treated with the alpha toxin of Staphylococcus aureus, strain "Wood-46", liberate substances which contain nitrogen, absorb at 280 mμ, and react with Folin phenol reagent. The susceptibility of different erythrocyte species to alpha toxin is correlated with (a) the quantity of reaction products released by toxin from the cells and (b) the degree of natural proteolytic activity possessed by the cells. Alpha toxin was, however, without effect upon albumin, fibrinogen, casein, and hemoglobin even when these proteins had been denatured with urea. In view of the evidence, it is suggested that the toxin is secreted by the Staphylococcus as an inactive protease which must be activated by another protease. The degree of activity of this protease in various red cell species would explain their differential sensitivity to alpha toxin.

scholarly journals SpoVG Regulates Cell Wall Metabolism and Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus Strain N315

2016 ◽  
Vol 60 (6) ◽  
pp. 3455-3461 ◽  
Author(s):  
Xiaoyu Liu ◽  
Shijie Zhang ◽  
Baolin Sun
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Aureus Strain ◽  
Cell Wall Metabolism ◽  
Mobility Shift ◽  
Entire Family ◽  
Positive Role ◽  
Methicillin Resistant ◽  
Oxacillin Resistance ◽  
Mrsa Strains

Increasing cases of infections caused by methicillin-resistantStaphylococcus aureus(MRSA) strains in healthy individuals have raised concerns worldwide. MRSA strains are resistant to almost the entire family of β-lactam antibiotics due to the acquisition of an extra penicillin-binding protein, PBP2a. Studies have shown thatspoVGis involved in oxacillin resistance, while the regulatory mechanism remains elusive. In this study, we have found that SpoVG plays a positive role in oxacillin resistance through promoting cell wall synthesis and inhibiting cell wall degradation in MRSA strain N315. Deletion ofspoVGin strain N315 led to a significant decrease in oxacillin resistance and a dramatic increase in Triton X-100-induced autolytic activity simultaneously. Real-time quantitative reverse transcription-PCR revealed that the expression of 8 genes related to cell wall metabolism or oxacillin resistance was altered in thespoVGmutant. Electrophoretic mobility shift assay indicated that SpoVG can directly bind to the putative promoter regions oflytN(murein hydrolase),femA, andlytSR(the two-component system). These findings suggest a molecular mechanism in which SpoVG modulates oxacillin resistance by regulating cell wall metabolism in MRSA.

Structure of the Cell Wall of Staphylococcus aureus Strain Copenhagen. VI. The Soluble Glycopeptide and Its Sequential Degradation by Peptidases*

Biochemistry ◽  
1965 ◽  
Vol 4 (10) ◽  
pp. 2245-2254 ◽  
Author(s):  
J. M. Ghuysen ◽  
D. J. Tipper ◽  
Claire H. Birge ◽  
J. L. Strominger
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Aureus Strain

scholarly journals Inhibition of Staphylococcus aureus Cell Wall Biosynthesis by Desleucyl-Oritavancin: a Quantitative Peptidoglycan Composition Analysis by Mass Spectrometry

2017 ◽  
Vol 199 (15) ◽  
Author(s):  
James D. Chang ◽  
Erin E. Foster ◽  
Aanchal N. Thadani ◽  
Alejandro J. Ramirez ◽  
Sung Joon Kim
Keyword(s):  
Mass Spectrometry ◽  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Binding Site ◽  
Mode Of Action ◽  
Composition Analysis ◽  
Edman Degradation ◽  
Glycopeptide Antibiotics ◽  
Content Type ◽  
The Cross

ABSTRACT Oritavancin is a lipoglycopeptide antibiotic that exhibits potent activities against vancomycin-resistant Gram-positive pathogens. Oritavancin differs from vancomycin by a hydrophobic side chain attached to the drug disaccharide, which forms a secondary binding site to enable oritavancin binding to the cross-linked peptidoglycan in the cell wall. The mode of action of secondary binding site was investigated by measuring the changes in the peptidoglycan composition of Staphylococcus aureus grown in the presence of desleucyl-oritavancin at subinhibitory concentration using liquid chromatography-mass spectrometry (LC-MS). Desleucyl-oritavancin is an Edman degradation product of oritavancin that exhibits potent antibacterial activities despite the damaged d-Ala–d-Ala binding site due to its functional secondary binding site. Accurate quantitative peptidoglycan composition analysis based on 83 muropeptide ions determined that cell walls of S. aureus grown in the presence of desleucyl-oritavancin showed a reduction of peptidoglycan cross-linking, increased muropeptides with a tetrapeptide-stem structure, decreased O-acetylation of MurNAc, and increased N-deacetylation of GlcNAc. The changes in peptidoglycan composition suggest that desleucyl-oritavancin targets the peptidoglycan template to induce cell wall disorder and interferes with cell wall maturation. IMPORTANCE Oritavancin is a lipoglycopeptide antibiotic with a secondary binding site that targets the cross-linked peptidoglycan bridge structure in the cell wall. Even after the loss of its primary d-Ala–d-Ala binding site through Edman degradation, desleucyl-oritavancin exhibits potent antimicrobial activities through its still-functioning secondary binding site. In this study, we characterized the mode of action for desleucyl-oritavancin's secondary binding site using LC-MS. Peptidoglycan composition analysis of desleucyl-oritavancin-treated S. aureus was performed by determining the relative abundances of 83 muropeptide ions matched from a precalculated library through integrating extracted ion chromatograms. Our work highlights the use of quantitative peptidoglycan composition analysis by LC-MS to provide insights into the mode of action of glycopeptide antibiotics.

The Peptide Subunit Nα-(L-Alanyl-D-isoglutaminyl)-L-lysyl -D-alanine in Cell Wall Peptidoglycans of Staphylococcus aureus Strain Copenhagen, Micrococcus roseus R 27, and Sreptococcus pyogenes Group A, Type 14

Biochemistry ◽  
1966 ◽  
Vol 5 (12) ◽  
pp. 3748-3764 ◽  
Author(s):  
Emilio Munoz ◽  
Jean-Marie Ghuysen ◽  
Melina Leyh-Bouille ◽  
Jean-Francois Petit ◽  
Hans Heymann ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Aureus Strain ◽  
Group A ◽  
Micrococcus Roseus

scholarly journals Transcriptional Profiling Reveals that Daptomycin Induces the Staphylococcus aureus Cell Wall Stress Stimulon and Genes Responsive to Membrane Depolarization

2007 ◽  
Vol 52 (3) ◽  
pp. 980-990 ◽  
Author(s):  
Arunachalam Muthaiyan ◽  
Jared A. Silverman ◽  
Radheshyam K. Jayaswal ◽  
Brian J. Wilkinson
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Mode Of Action ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Transcriptional Profiling ◽  
Wall Stress ◽  
Membrane Depolarization ◽  
Transcriptional Responses ◽  
Cell Wall Stress

ABSTRACT Daptomycin is a lipopeptide antibiotic that has recently been approved for treatment of gram-positive bacterial infections. The mode of action of daptomycin is not yet entirely clear. To further understand the mechanism transcriptomic analysis of changes in gene expression in daptomycin-treated Staphylococcus aureus was carried out. The expression profile indicated that cell wall stress stimulon member genes (B. J. Wilkinson, A. Muthaiyan, and R. K. Jayaswal, Curr. Med. Chem. Anti-Infect. Agents 4:259-276, 2005) were significantly induced by daptomycin and by the cell wall-active antibiotics vancomycin and oxacillin. Comparison of the daptomycin response of a two-component cell wall stress stimulon regulator VraSR mutant, S. aureus KVR, to its parent N315 showed diminished expression of the cell wall stress stimulon in the mutant. Daptomycin has been proposed to cause membrane depolarization, and the transcriptional responses to carbonyl cyanide m-chlorophenylhydrazone (CCCP) and nisin were determined. Transcriptional profiles of the responses to these antimicrobial agents showed significantly different patterns compared to those of the cell wall-active antibiotics, including little or no induction of the cell wall stress stimulon. However, there were a significant number of genes induced by both CCCP and daptomycin that were not induced by oxacillin or vancomycin, so the daptomycin transcriptome probably reflected a membrane depolarizing activity of this antimicrobial also. The results indicate that inhibition of peptidoglycan biosynthesis, either directly or indirectly, and membrane depolarization are parts of the mode of action of daptomycin.

scholarly journals Structure of the Cell Wall of Staphylococcus aureus, Strain Copenhagen. IV. The Teichoic Acid-Glycopeptide Complex*

Biochemistry ◽  
1965 ◽  
Vol 4 (3) ◽  
pp. 474-485 ◽  
Author(s):  
Jean-Marie Ghuysen ◽  
Donald J. Tipper ◽  
Jack L. Strominger
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Teichoic Acid ◽  
Aureus Strain

scholarly journals Truncation of Fibronectin-Binding Proteins in Staphylococcus aureus Strain Newman Leads to Deficient Adherence and Host Cell Invasion Due to Loss of the Cell Wall Anchor Function

2004 ◽  
Vol 72 (12) ◽  
pp. 7155-7163 ◽  
Author(s):  
Matthias Grundmeier ◽  
Muzaffar Hussain ◽  
Petra Becker ◽  
Christine Heilmann ◽  
Georg Peters ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Host Cell ◽  
Cell Invasion ◽  
Binding Proteins ◽  
Stop Codon ◽  
Aureus Strain ◽  
Host Cell Invasion ◽  
Fibronectin Receptor ◽  
Fibronectin Binding

ABSTRACT Staphylococcus aureus fibronectin-binding proteins (FnBPs) play a critical role in S. aureus pathogenesis. FnBPs mediate adhesion to fibronectin and invasion of mammalian cells, including epithelial, endothelial, and fibroblastic cells, by fibronectin bridging to the host cell fibronectin receptor integrin (α5)β1. Strain Newman is a laboratory strain frequently used for genetic, functional, and in vivo studies. However, despite pronounced production of FnBPs, strain Newman is only weakly adherent to immobilized Fn and weakly invasive. We examined whether these effects are due to a structural difference of FnBPs. Here, we show that both fnbA Newman and fnbB Newman contain a centrally located point mutation resulting in a stop codon. This leads to a truncation of both FnBPs at the end of the C domain at identical positions. Most likely, the stop codon occurred first in fnbB Newman and was subsequently transferred to fnbA Newman by replacement of the entire region encompassing the C, D, and W domains with the respective sequence of fnbB Newman. Using heterologous expression in Staphylococcus carnosus, we found that truncated FnBPs were completely secreted into the culture medium and not anchored to the cell wall, since they lack the sortase motif (LPETG). Consequently, this led to a loss of FnBP-dependent functions, such as strong adhesion to immobilized fibronectin, binding of fibrinogen, and host cell invasion. This mutation may explain some of the earlier reported conflicting data with strain Newman. Thus, care should be taken when drawing negative conclusions about the role of FnBPs as a virulence factor in a given model.

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