ArticleAntimicrobial agents and chemotherapy2016
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.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Impact on daptomycin resistance using combination of daptomycin plus ceftaroline in daptomycin-susceptible and -resistantFEMS microbes · 2026Article
- Extended-Spectrum β-Lactamase-ProducingAntibiotics (Basel, Switzerland) · 2025Review
- Expression ofmBio · 2025Article
- PBP4 is required for serum-induced cell wall thickening and antibiotic tolerance inAntimicrobial agents and chemotherapy · 2024Article
- ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics.Nature reviews. Microbiology · 2024Review
- Ceftaroline Fosamil for the Treatment of Methicillin-Resistant Staphylococcus Aureus Bacteremia: A Real-World Comparative Clinical Outcomes Study.Drugs - real world outcomes · 2024Article
- New Antimicrobials and New Therapy Strategies for Endocarditis: Weapons That Should Be Defended.Journal of clinical medicine · 2023Review
- Nafcillin Augmentation of Daptomycin and Cathelicidin LL-37 Killing of Methicillin-resistant Staphylococcus epidermidis: Foundations of Successful Therapy of Endocarditis.International journal of antimicrobial agents · 2023Article
- Growth Arrest of Staphylococcus aureus Induces Daptomycin Tolerance via Cell Wall Remodelling.mBio · 2023Article
- Synergistic Inhibition of MRSA by Chenodeoxycholic Acid and Carbapenem Antibiotics.Antibiotics (Basel, Switzerland) · 2022Article
- An optimized antimicrobial peptide analog acts as an antibiotic adjuvant to reverse methicillin-resistant Staphylococcus aureus.NPJ science of food · 2022Article
- Proteomic Correlates of Enhanced Daptomycin Activity following β-Lactam Preconditioning in Daptomycin-Resistant, Methicillin-Resistant Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2022Article
- The Role ofAntimicrobial agents and chemotherapy · 2022Article
- Current Paradigms of Combination Therapy in Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia: Does it Work, Which Combination, and For Which Patients?Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Review
- β-Lactam-Induced Cell Envelope Adaptations, Not Solely Enhanced Daptomycin Binding, Underlie Daptomycin-β-Lactam Synergy in Methicillin-Resistant Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2021Article
- Dalbavancin exposure in vitro selects for dalbavancin-non-susceptible and vancomycin-intermediate strains of methicillin-resistant Staphylococcus aureus.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2021Article
- Cell Membrane Adaptations Mediate β-Lactam-Induced Resensitization of Daptomycin-Resistant (DAP-R)Microorganisms · 2021Article
- Removal of peptidoglycan and inhibition of active cellular processes leads to daptomycin tolerance in Enterococcus faecalis.PloS one · 2021Article
- Prolonged Exposure to β-Lactam Antibiotics Reestablishes Susceptibility of Daptomycin-Nonsusceptible Staphylococcus aureus to Daptomycin.Antimicrobial agents and chemotherapy · 2020Article
- Multitarget Approaches against Multiresistant Superbugs.ACS infectious diseases · 2020Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The activity of daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA) is enhanced in the presence of β-lactam antibiotics. This effect is more pronounced with β-lactam antibiotics that exhibit avid binding to penicillin binding protein 1 (PBP1). Here, we present evidence that PBP1 has a significant role in responding to DAP-induced stress on the cell. Expression of the pbpA transcript, encoding PBP1, was specifically induced by DAP exposure whereas expression of pbpB, pbpC, and pbpD, encoding PBP2, PBP3, and PBP4, respectively, remained unchanged. Using a MRSA COL strain with pbpA under an inducible promoter, increased pbpA transcription was accompanied by reduced susceptibility to, and killing by, DAP in vitro. Exposure to β-lactams that preferentially inactivate PBP1 was not associated with increased DAP binding, suggesting that synergy in the setting of anti-PBP1 pharmacotherapy results from increased DAP potency on a per-molecule basis. Combination exposure in an in vitro pharmacokinetic/pharmacodynamic model system with β-lactams that preferentially inactivate PBP1 (DAP-meropenem [MEM] or DAP-imipenem [IPM]) resulted in more-rapid killing than did combination exposure with DAP-nafcillin (NAF) (nonselective), DAP-ceftriaxone (CRO) or DAP-cefotaxime (CTX) (PBP2 selective), DAP-cefaclor (CEC) (PBP3 selective), or DAP-cefoxitin (FOX) (PBP4 selective). Compared to β-lactams with poor PBP1 binding specificity, exposure of S. aureus to DAP plus PBP1-selective β-lactams resulted in an increased frequency of septation and cell wall abnormalities. These data suggest that PBP1 activity may contribute to survival during DAP-induced metabolic stress. Therefore, targeted inactivation of PBP1 may enhance the antimicrobial efficiency of DAP, supporting the use of DAP-β-lactam combination therapy for serious MRSA infections, particularly when the β-lactam undermines the PBP1-mediated compensatory response.
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