ArticlePloS one2011
Whole genome sequencing and complete genetic analysis reveals novel pathways to glycopeptide resistance in Staphylococcus aureus.
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 44 papers.
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Who cites it
44 citing papers in PubMed, 73 citations in OpenAlex.
- Genome-wide screen identifies novel factors for surface protein cross-wall trafficking and cell envelope homeostasis inJournal of bacteriology · 2026Article
- Genome-wide screen identifies novel factors for surface protein cross-wall trafficking and cell envelope homeostasis inbioRxiv : the preprint server for biology · 2025Article
- sRNA-mediated crosstalk between cell wall stress and galactose metabolism in Staphylococcus aureus.Nucleic acids research · 2025Article
- YjbH contributes toVirulence · 2024Article
- Genetic and Phenotypic Changes Related to the Development ofAntibiotics (Basel, Switzerland) · 2024Article
- The Spx stress regulator confers high-level β-lactam resistance and decreases susceptibility to last-line antibiotics in methicillin-resistantAntimicrobial agents and chemotherapy · 2024Article
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- The Role of ArlRS and VraSR in Regulating Ceftaroline Hypersusceptibility in Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2021Article
- MazF toxin causes alterations in Staphylococcus aureus transcriptome, translatome and proteome that underlie bacterial dormancy.Nucleic acids research · 2021Article
- Regulatory circuits controlling Spx levels in Streptococcus mutans.Molecular microbiology · 2020Article
- YjbH Solubility Controls Spx inFrontiers in microbiology · 2020Article
- Regulation of virulence and antibiotic resistance in Gram-positive microbes in response to cell wall-active antibiotics.Current opinion in infectious diseases · 2019Review
- Roles and regulation of Spx family transcription factors in Bacillus subtilis and related species.Advances in microbial physiology · 2019Review
- The Role of Methionine Sulfoxide Reductases in Oxidative Stress Tolerance and Virulence ofAntioxidants (Basel, Switzerland) · 2018Review
- Genetic Diversity among Staphylococcus aureus Isolates Showing Oxacillin and/or Cefoxitin Resistance Not Linked to the Presence ofAntimicrobial agents and chemotherapy · 2018Article
- Whole-Genome Sequencing and Genetic Analysis Reveal Novel Stress Responses to Individual Constituents of Essential Oils in Escherichia coli.Applied and environmental microbiology · 2018Article
- Both exo- and endo-nucleolytic activities of RNase J1 from Staphylococcus aureus are manganese dependent and active on triphosphorylated 5'-ends.RNA biology · 2017Article
- Vancomycin Resistance inThe Yale journal of biology and medicine · 2017Review
- A scalable metabolite supplementation strategy against antibiotic resistant pathogen Chromobacterium violaceum induced by NADBMC systems biology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The precise mechanisms leading to the emergence of low-level glycopeptide resistance in Staphylococcus aureus are poorly understood. In this study, we used whole genome deep sequencing to detect differences between two isogenic strains: a parental strain and a stable derivative selected stepwise for survival on 4 µg/ml teicoplanin, but which grows at higher drug concentrations (MIC 8 µg/ml). We uncovered only three single nucleotide changes in the selected strain. Nonsense mutations occurred in stp1, encoding a serine/threonine phosphatase, and in yjbH, encoding a post-transcriptional negative regulator of the redox/thiol stress sensor and global transcriptional regulator, Spx. A missense mutation (G45R) occurred in the histidine kinase sensor of cell wall stress, VraS. Using genetic methods, all single, pairwise combinations, and a fully reconstructed triple mutant were evaluated for their contribution to low-level glycopeptide resistance. We found a synergistic cooperation between dual phospho-signalling systems and a subtle contribution from YjbH, suggesting the activation of oxidative stress defences via Spx. To our knowledge, this is the first genetic demonstration of multiple sensor and stress pathways contributing simultaneously to glycopeptide resistance development. The multifactorial nature of glycopeptide resistance in this strain suggests a complex reprogramming of cell physiology to survive in the face of drug challenge.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.