ArticleNature microbiology2019
Genomic identification of cryptic susceptibility to penicillins and β-lactamase inhibitors in methicillin-resistant Staphylococcus aureus.
Article in Nature microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 67 citations in OpenAlex.
- Genomic investigation and clinical correlates of theAntimicrobial agents and chemotherapy · 2024Trial
- An Achilles' heel for methicillin-resistantAntimicrobial agents and chemotherapy · 2026Review
- Description of high-altitude, cold-adaptive, metabolically versatileMicrobiology spectrum · 2025Article
- Efficacy of Essential Oil of Algrizea minor Sobral, Faria & Proença (Myrtaceae) in Combating Methicillin-resistant Staphylococcus aureus: Antibacterial and Virulence Modulation Studies Conducted In Vitro and In Vivo.Chemistry & biodiversity · 2025Article
- Dynamic Profiling of Penicillin-Binding Protein 2a (PBP2a)-Positive Extracellular Vesicles: Implications for Early Diagnosis and Treatment Monitoring of Methicillin-Resistant Staphylococcus Aureus Infections.Journal of extracellular vesicles · 2025Article
- Article
- Phenotypic and genotypic correlates of the sodium bicarbonate-responsive phenotype among methicillin-resistant Staphylococcus aureus isolates from skin and soft-tissue infections.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2025Article
- Potential of the livestock industry environment as a reservoir for spreading antimicrobial resistance.Open veterinary journal · 2025Review
- Bicarbonate Within: A Hidden Modulator of Antibiotic Susceptibility.Antibiotics (Basel, Switzerland) · 2025Review
- Emerging Challenges in Methicillin Resistance of Coagulase-Negative Staphylococci.Antibiotics (Basel, Switzerland) · 2025Article
- Article
- Multimodal nanoimmunotherapy engages neutrophils to eliminate Staphylococcus aureus infections.Nature nanotechnology · 2024Article
- Antimicrobial Resistance in Livestock: A Serious Threat to Public Health.Antibiotics (Basel, Switzerland) · 2024Review
- Innovative Biomedical and Technological Strategies for the Control of Bacterial Growth and Infections.Biomedicines · 2024Review
- Case Commentary: The hidden side of oxacillin resistance inAntimicrobial agents and chemotherapy · 2023Article
- Cryptic susceptibility to penicillin/β-lactamase inhibitor combinations in emerging multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages.Nature communications · 2023Article
- Phenotypic and genomic characteristics of oxacillin-susceptible mecA-positive Staphylococcus aureus, rapid selection of high-level resistance to beta-lactams.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2023Article
- Ciprofloxacin and Tetracycline Resistance Cause Collateral Sensitivity to Aminoglycosides inAntibiotics (Basel, Switzerland) · 2023Article
- Impact of Bicarbonate on PBP2a Production, Maturation, and Functionality in Methicillin-ResistantAntimicrobial agents and chemotherapy · 2023Article
- Transcription tuned by S-nitrosylation underlies a mechanism for Staphylococcus aureus to circumvent vancomycin killing.Nature communications · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 11 institutions in 5 countries.
Funding
Abstract
Antibiotic resistance in bacterial pathogens threatens the future of modern medicine. One such resistant pathogen is methicillin-resistant Staphylococcus aureus (MRSA), which is resistant to nearly all β-lactam antibiotics, limiting treatment options. Here, we show that a significant proportion of MRSA isolates from different lineages, including the epidemic USA300 lineage, are susceptible to penicillins when used in combination with β-lactamase inhibitors such as clavulanic acid. Susceptibility is mediated by a combination of two different mutations in the mecA promoter region that lowers mecA-encoded penicillin-binding protein 2a (PBP2a) expression, and in the majority of isolates by either one of two substitutions in PBP2a (E246G or M122I) that increase the affinity of PBP2a for penicillin in the presence of clavulanic acid. Treatment of S. aureus infections in wax moth and mouse models shows that penicillin/β-lactamase inhibitor susceptibility can be exploited as an effective therapeutic choice for 'susceptible' MRSA infection. Finally, we show that isolates with the PBP2a E246G substitution have a growth advantage in the presence of penicillin but the absence of clavulanic acid, which suggests that penicillin/β-lactamase susceptibility is an example of collateral sensitivity (resistance to one antibiotic increases sensitivity to another). Our findings suggest that widely available and currently disregarded antibiotics could be effective in a significant proportion of MRSA infections.
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.