ArticlePloS one2013
Targeting of PBP1 by β-lactams determines recA/SOS response activation in heterogeneous MRSA clinical strains.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
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- An emerging zoonosis: molecular detection of multidrug-methicillin resistant Staphylococcus aureus from butchers' knives, livestock products and contact surfaces.Veterinary research communications · 2024Article
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- Deciphering the genetic network and programmed regulation of antimicrobial resistance in bacterial pathogens.Frontiers in cellular and infection microbiology · 2022Review
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- Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 4:EFSA journal. European Food Safety Authority · 2021Article
- RexAB Promotes the Survival of Staphylococcus aureus Exposed to Multiple Classes of Antibiotics.Antimicrobial agents and chemotherapy · 2021Article
- Carbapenems drive the collateral resistance to ceftaroline in cystic fibrosis patients with MRSA.Communications biology · 2020Article
- Impaired Alanine Transport or Exposure to d-Cycloserine Increases the Susceptibility of MRSA to β-lactam Antibiotics.The Journal of infectious diseases · 2020Article
- Article
- Regulation of virulence and antibiotic resistance in Gram-positive microbes in response to cell wall-active antibiotics.Current opinion in infectious diseases · 2019Review
- The Role of Antibiotics in Modulating Virulence in Staphylococcus aureus.Clinical microbiology reviews · 2017Review
- Antibiotics trigger initiation of SCCmec transfer by inducing SOS responses.Nucleic acids research · 2017Article
- Penicillin Binding Protein 1 Is Important in the Compensatory Response of Staphylococcus aureus to Daptomycin-Induced Membrane Damage and Is a Potential Target for β-Lactam-Daptomycin Synergy.Antimicrobial agents and chemotherapy · 2016Article
- Antimicrobial heteroresistance: an emerging field in need of clarity.Clinical microbiology reviews · 2015Review
- Ceftaroline is active against heteroresistant methicillin-resistant Staphylococcus aureus clinical strains despite associated mutational mechanisms and intermediate levels of resistance.Antimicrobial agents and chemotherapy · 2014Article
- TCA cycle-mediated generation of ROS is a key mediator for HeR-MRSA survival under β-lactam antibiotic exposure.PloS one · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The SOS response, a conserved regulatory network in bacteria that is induced in response to DNA damage, has been shown to be associated with the emergence of resistance to antibiotics. Previously, we demonstrated that heterogeneous (HeR) MRSA strains, when exposed to sub-inhibitory concentrations of oxacillin, were able to express a homogeneous high level of resistance (HoR). Moreover, we showed that oxacillin appeared to be the triggering factor of a β-lactam-mediated SOS response through lexA/recA regulators, responsible for an increased mutation rate and selection of a HoR derivative. In this work, we demonstrated, by selectively exposing to β-lactam and non-β-lactam cell wall inhibitors, that PBP1 plays a critical role in SOS-mediated recA activation and HeR-HoR selection. Functional analysis of PBP1 using an inducible PBP1-specific antisense construct showed that PBP1 depletion abolished both β-lactam-induced recA expression/activation and increased mutation rates during HeR/HoR selection. Furthermore, based on the observation that HeR/HoR selection is accompanied by compensatory increases in the expression of PBP1,-2, -2a, and -4, our study provides evidence that a combination of agents simultaneously targeting PBP1 and either PBP2 or PBP2a showed both in-vitro and in-vivo efficacy, thereby representing a therapeutic option for the treatment of highly resistant HoR-MRSA strains. The information gathered from these studies contributes to our understanding of β-lactam-mediated HeR/HoR selection and provides new insights, based on β-lactam synergistic combinations, that mitigate drug resistance for the treatment of MRSA infections.
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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.