ArticleACS chemical biology2013
Inhibition of WTA synthesis blocks the cooperative action of PBPs and sensitizes MRSA to β-lactams.
Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
111 citing papers in PubMed, 212 citations in OpenAlex.
- An Achilles' heel for methicillin-resistantAntimicrobial agents and chemotherapy · 2026Review
- Structure-based computational investigation of potential TarA inhibitors in Staphylococcus aureus.Molecular diversity · 2026Article
- Wall teichoic acids regulate peptidoglycan synthesis to maintain rod shape in Bacillus subtilis.Nature microbiology · 2026Article
- Phage Intolerance Impacts Antibiotic Susceptibility and Virulence in Staphylococcus aureus.Current microbiology · 2026Article
- Article
- Synergistic action of peptidoglycan and teichoic acid synthesis inhibitors leads to cell death by oxidative damage.Communications biology · 2026Article
- Evaluating the ability of in silico identified hit compounds to bind Staphylococcus aureus LcpAMolecular diversity · 2026Article
- Mechanistic studies on the effect of berberine on methicillin-resistant Staphylococcus aureus drug resistance through modulation of wall teichoteic acid.Scientific reports · 2025Article
- SpbR controls lipoteichoic acid length by directly inhibiting signal peptidase SpsB inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Design, synthesis and optimization of TarO inhibitors as multifunctional antibiotics against Methicillin-resistant Staphylococcus aureus.npj antimicrobials and resistance · 2025Article
- Cryo-EM analyses unveil details of mechanism and targocil-II mediated inhibition of S. aureus WTA transporter TarGH.Nature communications · 2025Article
- NaHCO3 modulates the bla operon and β-lactam susceptibility in borderline oxacillin-resistant Staphylococcus aureus (BORSA).The Journal of antimicrobial chemotherapy · 2025Article
- Berberine inhibits the tarO gene to impact MRSA cell wall synthesis.Scientific reports · 2025Article
- Bicarbonate Within: A Hidden Modulator of Antibiotic Susceptibility.Antibiotics (Basel, Switzerland) · 2025Review
- Combatting melioidosis with chemical synthetic lethality.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Synergistic potential of LeuBMC microbiology · 2024Article
- Article
- Endophytes: a uniquely tailored source of potential antibiotic adjuvants.Archives of microbiology · 2024Review
- Sensitizing methicillin-resistantAntimicrobial agents and chemotherapy · 2024Article
- A mobile CRISPRi collection enables genetic interaction studies for the essential genes of Escherichia coli.Cell reports methods · 2024Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Rising drug resistance is limiting treatment options for infections by methicillin-resistant Staphylococcus aureus (MRSA). Herein we provide new evidence that wall teichoic acid (WTA) biogenesis is a remarkable antibacterial target with the capacity to destabilize the cooperative action of penicillin-binding proteins (PBPs) that underlie β-lactam resistance in MRSA. Deletion of gene tarO, encoding the first step of WTA synthesis, resulted in the restoration of sensitivity of MRSA to a unique profile of β-lactam antibiotics with a known selectivity for penicillin binding protein 2 (PBP2). Of these, cefuroxime was used as a probe to screen for previously approved drugs with a cryptic capacity to potentiate its activity against MRSA. Ticlopidine, the antiplatelet drug Ticlid, strongly potentiated cefuroxime, and this synergy was abolished in strains lacking tarO. The combination was also effective in a Galleria mellonella model of infection. Using both genetic and biochemical strategies, we determined the molecular target of ticlopidine as the N-acetylglucosamine-1-phosphate transferase encoded in gene tarO and provide evidence that WTA biogenesis represents an Achilles heel supporting the cooperative function of PBP2 and PBP4 in creating highly cross-linked muropeptides in the peptidoglycan of S. aureus. This approach represents a new paradigm to tackle MRSA infection.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.