scholarly journals Cell Wall Composition and Decreased Autolytic Activity and Lysostaphin Susceptibility of Glycopeptide-Intermediate Staphylococcus aureus

2004 ◽  
Vol 48 (10) ◽  
pp. 3749-3757 ◽  
Author(s):  
Jennifer L. Koehl ◽  
Arunachalam Muthaiyan ◽  
Radheshyam K. Jayaswal ◽  
Kerstin Ehlert ◽  
Harald Labischinski ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Walls ◽  
Northern Blot Analysis ◽  
Teichoic Acid ◽  
Cell Wall Composition ◽  
Wall Teichoic Acid ◽  
Whole Cells ◽  
Autolytic Activity ◽  
Increased Susceptibility

ABSTRACT The cell wall composition and autolytic properties of passage-selected glycopeptide-intermediate Staphylococcus aureus (GISA) isolates and their parent strains were studied in order to investigate the mechanism of decreased vancomycin susceptibility. GISA had relatively modest changes in peptidoglycan composition involving peptidoglycan interpeptide bridges and somewhat decreased cross-linking compared to that of parent strains. The cell wall phosphorus content of GISA strains was lower than that of susceptible parent strains, indicating somewhat lower wall teichoic acid levels in the GISA strains. Similar to whole cells, isolated crude cell walls retaining autolytic activity of GISA had drastically reduced autolytic activity compared to that of parent strains, and this arose early in the development of the GISA phenotype. This was due to an alteration in the autolytic enzymes of GISA as revealed by normal susceptibility of GISA-purified cell walls to parental strain autolysin extract and lower activity and altered peptidoglycan hydrolase activity profiles in GISA autolysin extracts compared to those of parent strains. Northern blot analysis indicated that expression of atl, the major autolysin gene, was significantly downregulated in a GISA strain compared to that of its parent strain. In contrast to whole cells, which showed decreased lysostaphin susceptibility, purified cell walls of GISA showed increased susceptibility to lysostaphin. We suggest that in our GISA strains, decreased autolytic activity is involved in the tolerance of vancomycin and the activities of endogenous autolysins are important in conferring sensitivity to lysostaphin on whole cells.

scholarly journals Glycosylation of Staphylococcus aureus cell wall teichoic acid is influenced by environmental conditions

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Noëlle Mistretta ◽  
Marina Brossaud ◽  
Fabienne Telles ◽  
Violette Sanchez ◽  
Philippe Talaga ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Environmental Conditions ◽  
Teichoic Acid ◽  
Wall Teichoic Acid

scholarly journals YycH and YycI Regulate Expression of Staphylococcus aureus Autolysins by Activation of WalRK Phosphorylation

2020 ◽  
Vol 8 (6) ◽  
pp. 870
Author(s):  
Mike Gajdiss ◽  
Ian R. Monk ◽  
Ute Bertsche ◽  
Janina Kienemund ◽  
Tanja Funk ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Teichoic Acid ◽  
Regulatory System ◽  
Regulatory Function ◽  
Wall Teichoic Acid ◽  
Dependent Cell ◽  
Severe Infections

Staphylococcus aureus is a facultative pathogen that can encode numerous antibiotic resistance and immune evasion genes and can cause severe infections. Reduced susceptibility to last resort antibiotics such as vancomycin and daptomycin is often associated with mutations in walRK, an essential two-component regulatory system (TCS). This study focuses on the WalK accessory membrane proteins YycH and YycI and their influence on WalRK phosphorylation. Depletion of YycH and YycI by antisense RNA caused an impaired autolysis, indicating a positive regulatory function on WalK as has been previously described. Phosphorylation assays with full-length recombinant proteins in phospholipid liposomes showed that YycH and YycI stimulate WalK activity and that both regulatory proteins are needed for full activation of the WalK kinase. This was validated in vivo through examining the phosphorylation status of WalR using Phos-tag SDS-PAGE with a yycHI deletion mutant exhibiting reduced levels of phosphorylated WalR. In the yycHI knockdown strain, muropeptide composition of the cell wall was not affected, however, the wall teichoic acid content was increased. In conclusion, a direct modulation of WalRK phosphorylation activity by the accessory proteins YycH and YycI is reported both in vitro and in vivo. Taken together, our results show that YycH and YycI are important in the direct regulation of WalRK-dependent cell wall metabolism.

scholarly journals LcpB Is a Pyrophosphatase Responsible for Wall Teichoic Acid Synthesis and Virulence in Staphylococcus aureus Clinical Isolate ST59

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting Pan ◽  
Jing Guan ◽  
Yujie Li ◽  
Baolin Sun
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Molecular Mechanisms ◽  
Teichoic Acid ◽  
Acid Synthesis ◽  
Cell Wall Synthesis ◽  
Wall Teichoic Acid ◽  
Independent Manner ◽  
Methicillin Resistant

The community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes severe pandemics primarily consisting of skin and soft tissue infections. However, the underlying pathomechanisms of the bacterium are yet to fully understood. The present study identifies LcpB protein, which belongs to the LytR-A-Psr (LCP) family, is crucial for cell wall synthesis and virulence in S. aureus. The findings revealed that LcpB is a pyrophosphatase responsible for wall teichoic acid synthesis. The results also showed that LcpB regulates enzyme activity through specific key arginine sites in its LCP domain. Furthermore, knockout of lcpB in the CA-MRSA isolate ST59 resulted in enhanced hemolytic activity, enlarged of abscesses, and increased leukocyte infiltration. Meanwhile, we also found that LcpB regulates virulence in agr-independent manner and the key sites for pyrophosphatase of LcpB play critical roles in regulating the virulence. In addition, the results showed that the role of LcpB was different between methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). This study therefore highlights the dual role of LcpB in cell wall synthesis and regulation of virulence. These insights on the underlying molecular mechanisms can thus guide the development of novel anti-infective strategies.

scholarly journals The impact of Staphylococcus aureus cell wall glycosylation on langerin recognition and Langerhans cell activation

2020 ◽  
Author(s):  
A Hendriks ◽  
R van Dalen ◽  
S Ali ◽  
D Gerlach ◽  
GA van der Marel ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Activation ◽  
Teichoic Acid ◽  
Binding Studies ◽  
Wall Teichoic Acid ◽  
Linkage Position ◽  
Antigen Presenting ◽  
The Impact

AbstractStaphylococcus aureus is the leading cause of skin and soft tissue infections. It remains incompletely understood how skin-resident immune cells respond to S. aureus invasion and contribute to an effective immune response. Langerhans cells (LCs), the only professional antigen-presenting cell type in the epidermis, sense S. aureus through their pattern-recognition receptor langerin, triggering a pro-inflammatory response. Langerin specifically recognizes the β-1,4-linked N-acetylglucosamine (β-GlcNAc) modification, which requires the glycosyltransferase TarS, on the cell wall glycopolymer Wall Teichoic Acid (WTA). Recently, an alternative WTA glycosyltransferase, TarP, was identified in methicillin-resistant S. aureus strains belonging to clonal complexes (CC) 5 and CC398. TarP also modifies WTA with β-GlcNAc but at the C-3 position of the WTA ribitol phosphate (RboP) subunit. Here, we aimed to unravel the impact of β-GlcNAc linkage position for langerin binding and LC activation. In addition, we performed structure-binding studies using a small panel of unique chemically-synthesized WTA molecules to assess langerin-WTA binding requirements. Using FITC-labeled recombinant human langerin and genetically-modified S. aureus strains, we observed that langerin similarly recognized bacteria that produce either TarS- or TarP-modified WTA. Furthermore, using chemically-synthesized WTA, representative of the different S. aureus WTA glycosylation patterns, established that β-GlcNAc is sufficient to confer langerin binding. Functionally, tarP-expressing S. aureus induce increased cytokine production and maturation of in vitro-generated LCs compared to tarSexpressing S. aureus. Overall, our data suggest that LCs are able to sense all β-GlcNAc-WTA producing S. aureus strains, likely performing an important role as first responders upon S. aureus skin invasion.

scholarly journals Inactivation of the monofunctional peptidoglycan glycosyltransferase SgtB allowsStaphylococcus aureusto survive in the absence of lipoteichoic acid

2018 ◽  
Author(s):  
Eleni Karinou ◽  
Christopher F. Schuster ◽  
Manuel Pazos ◽  
Waldemar Vollmer ◽  
Angelika Gründling
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Teichoic Acid ◽  
Fold Increase ◽  
Lipoteichoic Acid ◽  
Wall Teichoic Acid ◽  
Anionic Polymers ◽  
Peptidoglycan Structure ◽  
Intimate Link ◽  
Inactivating Mutations

AbstractThe cell wall ofStaphylococcus aureusis composed of peptidoglycan and the anionic polymers lipoteichoic acid (LTA) and wall teichoic acid. LTA is required for growth and normal cell morphology inS. aureus.Strains lacking LTA are usually only viable when grown under osmotically stabilizing conditions or after the acquisition of compensatory mutations. LTA negative suppressor strains with inactivating mutations ingdpP, resulting in an increase in intracellular c-di-AMP levels, have been described previously. Here, we sought to identify factors other than c-di-AMP that allowS. aureusto survive without LTA. LTA-negative strains able to grow in un-supplemented medium were obtained and found to contain mutations insgtB, mazE, clpXorvraT. The growth improvement through mutations inmazEandsgtBwas confirmed by complementation analysis. We also show that anS. aureus sgtBtransposon mutant, inactivated for the monofunctional peptidoglycan glycosyltransferase SgtB, displays a 4-fold increase in the MIC towards a number of cell wall-targeting antibiotics, suggesting that alteration in the peptidoglycan structure could help bacteria compensate for the lack of LTA. Muropeptide analysis of peptidoglycan isolated from a WT andsgtBmutant strains did not reveal any sizable alternations in the peptidoglycan structure. In contrast, the peptidoglycan isolated from an LTA-negativeltaSmutant strain showed a significant reduction in the fraction of highly crosslinked peptidoglycan, which was partially rescued in thesgtB/ltaSdouble mutant suppressor strain. Taken together, these data point towards an important function of LTA in cell wall integrity through its requirement for proper peptidoglycan assembly.ImportanceThe bacterial cell wall acts as primary defence against environmental insults such as changes in osmolarity. It is also a vulnerable structure as defects in its synthesis can lead to growth arrest or cell death. The important human pathogenStaphylococcus aureushas a typical Gram-positive cell wall, which consists of peptidoglycan and the anionic polymers lipoteichoic acid (LTA) and wall teichoic acid. Several clinically relevant antibiotics inhibit the synthesis of peptidoglycan; hence it and teichoic acids are considered attractive targets for the development of new antimicrobials. We show that LTA is required for efficient peptidoglycan crosslinking inS. aureusand inactivation of a peptidoglycan glycosyltransferase can partially rescue this defect, altogether revealing an intimate link between peptidoglycan and LTA synthesis.

scholarly journals CHEMICAL BASIS FOR AN IMMUNOLOGICAL SPECIFICITY OF A STRAIN OF STAPHYLOCOCCUS AUREUS

1963 ◽  
Vol 117 (6) ◽  
pp. 925-935 ◽  
Author(s):  
William G. Juergens ◽  
Arnold R. Sanderson ◽  
Jack L. Strominger
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Degradation Product ◽  
Cell Walls ◽  
Horse Serum ◽  
Teichoic Acid ◽  
Aureus Strain ◽  
Chemical Basis ◽  
Immunological Specificity ◽  
Group A

Antisera, prepared against formalin-killed cells of Staphylococcus aureus, strain Copenhagen, agglutinated the cell walls of this strain. The agglutination was inhibited by the teichoic acid from the cell wall of this strain, by any degradation product of this teichoic acid which contained the α-acetylglucosaminyl-ribitol unit, by α-phenyl-acetylglucosaminide, and by N-acetylglucosamine, but not by a large number of other haptens related to the cell wall. In quantitative experiments, however, only 40 to 50 per cent of antibody adsorption to cell wall could be inhibited by teichoic acid or by N-acetylglucosamine. The α-acetylglucosaminyl-ribitol unit in the teichoic acid is, therefore, an important immunological determinant in the cell wall of this strain, although other immunological specificities may also exist. The cell walls were also agglutinated by heterologous antisera prepared against streptococcal Group A carbohydrate or against horse serum azophenyl-ß-acetylglucosaminide. The heterologous agglutination, however, was specific for the ß-acetylglucosaminyl-ribitol units in the teichoic acid.

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