ArticlePLoS pathogens2018
SpdC, a novel virulence factor, controls histidine kinase activity in Staphylococcus aureus.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 44 citations in OpenAlex.
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- Staphylococcus aureus cell wall maintenance - the multifaceted roles of peptidoglycan hydrolases in bacterial growth, fitness, and virulence.FEMS microbiology reviews · 2022Review
- Effect of spdC gene expression on virulence and antibiotic resistance in clinical Staphylococcus aureus isolates.International microbiology : the official journal of the Spanish Society for Microbiology · 2022Article
- Targeting the Achilles' Heel of Multidrug-ResistantInternational journal of molecular sciences · 2022Article
- Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria.Microorganisms · 2022Review
- Drug Resistance and Epigenetic Modulatory Potential of Epigallocatechin-3-Gallate Against Staphylococcus aureus.Current microbiology · 2022Article
- The W-Acidic Motif of Histidine Kinase WalK Is Required for Signaling and Transcriptional Regulation inFrontiers in microbiology · 2022Article
- The Role of SilX in Bacteriocin Production ofFrontiers in microbiology · 2022Article
- Two-Component Systems ofGenes · 2021Review
- Diversity in Sensing and Signaling of Bacterial Sensor Histidine Kinases.Biomolecules · 2021Review
- Regulated cleavage of glycan strands by the murein hydrolase SagB inJournal of bacteriology · 2021Article
- Structure and reconstitution of a hydrolase complex that may release peptidoglycan from the membrane after polymerization.Nature microbiology · 2021Article
- Single Amino Acid Replacements in RocA Disrupt Protein-Protein Interactions To Alter the Molecular Pathogenesis of Group AInfection and immunity · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The success of Staphylococcus aureus, as both a human and animal pathogen, stems from its ability to rapidly adapt to a wide spectrum of environmental conditions. Two-component systems (TCSs) play a crucial role in this process. Here, we describe a novel staphylococcal virulence factor, SpdC, an Abi-domain protein, involved in signal sensing and/or transduction. We have uncovered a functional link between the WalKR essential TCS and the SpdC Abi membrane protein. Expression of spdC is positively regulated by the WalKR system and, in turn, SpdC negatively controls WalKR regulon genes, effectively constituting a negative feedback loop. The WalKR system is mainly involved in controlling cell wall metabolism through regulation of autolysin production. We have shown that SpdC inhibits the WalKR-dependent synthesis of four peptidoglycan hydrolases, SceD, SsaA, LytM and AtlA, as well as impacting S. aureus resistance towards lysostaphin and cell wall antibiotics such as oxacillin and tunicamycin. We have also shown that SpdC is required for S. aureus biofilm formation and virulence in a murine septicemia model. Using protein-protein interactions in E. coli as well as subcellular localization in S. aureus, we showed that SpdC and the WalK kinase are both localized at the division septum and that the two proteins interact. In addition to WalK, our results indicate that SpdC also interacts with nine other S. aureus histidine kinases, suggesting that this membrane protein may act as a global regulator of TCS activity. Indeed, using RNA-Seq analysis, we showed that SpdC controls the expression of approximately one hundred genes in S. aureus, many of which belong to TCS regulons.
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