ArticlePloS one2016
Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Resistant to Fifth-Generation Cephalosporins Reveals Potential Non-mecA Mechanisms of Resistance.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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Who cites it
40 citing papers in PubMed, 66 citations in OpenAlex.
- Breaking the antimicrobial resistance dilemma: marine natural products, a treasure trove for the development of new anti-Marine life science & technology · 2026Review
- Penicillin-Binding Protein-4 (PBP4) ofMicroorganisms · 2026Review
- A comprehensive review of emerging therapeutic strategies against methicillin-resistantFrontiers in microbiology · 2026Review
- Machine learning and cheminformatics-based Identification of lichen-derived compounds targeting mutant PBP4Molecular diversity · 2025Article
- Molecular resistance mechanisms to newly approved antibiotics (2017-2025) in WHO priority pathogens.Frontiers in microbiology · 2025Review
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- Beyond the Wild MRSA: Genetic Features and Phylogenomic Review ofMicroorganisms · 2023Review
- Anti-MRSA and Biological Activities of Propolis Concentrations Loaded to Chitosan Nanoemulsion for Pharmaceutics Applications.Pharmaceutics · 2023Article
- Molecular Determinants of β-Lactam Resistance in Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2023Review
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- Synergistic Combinations of FDA-Approved Drugs with Ceftobiprole against Methicillin-Resistant Staphylococcus aureus.Microbiology spectrum · 2023Article
- A Nonclassical Mechanism of β-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus and Its Effect on Virulence.Microbiology spectrum · 2022Article
- Reduced Ceftaroline Susceptibility among Invasive MRSA Infections in Children: a Clinical and Genomic Investigation.Antimicrobial agents and chemotherapy · 2022Article
- Identification ofAntibiotics (Basel, Switzerland) · 2022Article
- Molecular Mechanisms of Drug Resistance inInternational journal of molecular sciences · 2022Review
- An Interplay of Multiple Positive and Negative Factors Governs Methicillin Resistance in Staphylococcus aureus.Microbiology and molecular biology reviews : MMBR · 2022Review
- Article
- Loss of GdpP Function in Staphylococcus aureus Leads to β-Lactam Tolerance and Enhanced Evolution of β-Lactam Resistance.Antimicrobial agents and chemotherapy · 2022Article
- Characterization and Clonal Diffusion of Ceftaroline Non-Susceptible MRSA in Two Hospitals in Central Italy.Antibiotics (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Fifth-generation cephalosporins, ceftobiprole and ceftaroline, are promising drugs for treatment of bacterial infections from methicillin-resistant Staphylococcus aureus (MRSA). These antibiotics are able to bind native PBP2a, the penicillin-binding protein encoded by the mecA resistance determinant that mediates broad class resistance to nearly all other beta-lactam antibiotics, at clinically achievable concentrations. Mechanisms of resistance to ceftaroline based on mecA mutations have been previously described. Here we compare the genomes of 11 total parent-daughter strains of Staphylococcus aureus for which specific selection by serial passaging with ceftaroline or ceftobiprole was used to identify novel non-mecA mechanisms of resistance. All 5 ceftaroline-resistant strains, derived from 5 different parental strains, contained mutations directly upstream of the pbp4 gene (coding for the PBP4 protein), including four with the same thymidine insertion located 377 nucleotides upstream of the promoter site. In 4 of 5 independent ceftaroline-driven selections, we also isolated mutations to the same residue (Asn138) in PBP4. In addition, mutations in additional candidate genes such as ClpX endopeptidase, PP2C protein phosphatase and transcription terminator Rho, previously undescribed in the context of resistance to ceftaroline or ceftobiprole, were detected in multiple selections. These genomic findings suggest that non-mecA mechanisms, while yet to be encountered in the clinical setting, may also be important in mediating resistance to 5th-generation cephalosporins.
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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.