ArticlePloS one2011
Peptidoglycan crosslinking relaxation plays an important role in Staphylococcus aureus WalKR-dependent cell viability.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 87 citations in OpenAlex.
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- Cell splitting in Staphylococcus aureus is controlled by an adaptor protein facilitating degradation of a peptidoglycan hydrolase.PLoS genetics · 2025Article
- Combination therapy delays antimicrobial resistance after adaptive laboratory evolution ofAntimicrobial agents and chemotherapy · 2025Article
- Berberine inhibits the tarO gene to impact MRSA cell wall synthesis.Scientific reports · 2025Article
- Characterization of VldE (Spr1875), a Pneumococcal Two-State l,d-Endopeptidase with a Four-Zinc Cluster in the Active Site.ACS catalysis · 2024Article
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- DecipheringmSystems · 2024Article
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- Imbalance of peptidoglycan biosynthesis alters the cell surface charge ofCell surface (Amsterdam, Netherlands) · 2022Article
- Staphylococcus aureus cell wall maintenance - the multifaceted roles of peptidoglycan hydrolases in bacterial growth, fitness, and virulence.FEMS microbiology reviews · 2022Review
- Cervimycin-Resistant Staphylococcus aureus Strains Display Vancomycin-Intermediate Resistant Phenotypes.Microbiology spectrum · 2022Article
- Molecular Basis of Non-β-Lactam Antibiotics Resistance inAntibiotics (Basel, Switzerland) · 2022Review
- Targeting the Achilles' Heel of Multidrug-ResistantInternational journal of molecular sciences · 2022Article
- The WalRK Two-Component System Is Essential for Proper Cell Envelope Biogenesis in Clostridioides difficile.Journal of bacteriology · 2022Article
- The W-Acidic Motif of Histidine Kinase WalK Is Required for Signaling and Transcriptional Regulation inFrontiers in microbiology · 2022Article
- Recent Advances in Histidine Kinase-Targeted Antimicrobial Agents.Frontiers in chemistry · 2022Review
- The Role ofAntibiotics (Basel, Switzerland) · 2021Review
- Demonstration of the role of cell wall homeostasis inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The WalKR two-component system is essential for viability of Staphylococcus aureus, a major pathogen. We have shown that WalKR acts as the master controller of peptidoglycan metabolism, yet none of the identified regulon genes explain its requirement for cell viability. Transmission electron micrographs revealed cell wall thickening and aberrant division septa in the absence of WalKR, suggesting its requirement may be linked to its role in coordinating cell wall metabolism and cell division. We therefore tested whether uncoupling autolysin gene expression from WalKR-dependent regulation could compensate for its essential nature. Uncoupled expression of genes encoding lytic transglycosylases or amidases did not restore growth to a WalKR-depleted strain. We identified only two WalKR-regulon genes whose expression restored cell viability in the absence of WalKR: lytM and ssaA. Neither of these two genes are essential under our conditions and a ΔlytM ΔssaA mutant does not present any growth defect. LytM is a glycyl-glycyl endopeptidase, hydrolyzing the pentaglycine interpeptide crossbridge, and SsaA belongs to the CHAP amidase family, members of which such as LysK and LytA have been shown to have D-alanyl-glycyl endopeptidase activity, cleaving between the crossbridge and the stem peptide. Taken together, our results strongly suggest that peptidoglycan crosslinking relaxation through crossbridge hydrolysis plays a crucial role in the essential requirement of the WalKR system for cell viability.
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