ArticleThe Journal of infectious diseases2020
Impaired Alanine Transport or Exposure to d-Cycloserine Increases the Susceptibility of MRSA to β-lactam Antibiotics.
Article in The Journal of infectious diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Alanine Uptake Is Required to MaintainMicroorganisms · 2026Article
- Mutation of lipoprotein processing pathway geneAntimicrobial agents and chemotherapy · 2026Article
- D-alanine synthesis and exogenous alanine affect the antimicrobial susceptibility ofAntimicrobial agents and chemotherapy · 2025Article
- mSphere of Influence: Targeting bacterial signaling and metabolism to overcome antimicrobial resistance.mSphere · 2024Article
- Selection of Multi-Drug Targets against Drug-ResistantInternational journal of molecular sciences · 2023Article
- Article
- Alanine-Dependent TCA Cycle Promotion Restores the Zhongshengmycin-Susceptibility inInternational journal of molecular sciences · 2023Article
- Low-cost anti-mycobacterial drug discovery using engineered E. coli.Nature communications · 2022Article
- An Interplay of Multiple Positive and Negative Factors Governs Methicillin Resistance in Staphylococcus aureus.Microbiology and molecular biology reviews : MMBR · 2022Review
- Metabolomic Profiles of Multidrug-ResistantAnimals : an open access journal from MDPI · 2022Article
- Article
- VraCP regulates cell wall metabolism and antibiotic resistance in vancomycin-intermediate Staphylococcus aureus strain Mu50.The Journal of antimicrobial chemotherapy · 2021Article
- Feline Otitis Externa Caused by Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2021Article
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- Exploring amino acid and peptide transporters as therapeutic targets to attenuate virulence and antibiotic resistance in Staphylococcus aureus.PLoS pathogens · 2021Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
Prolonging the clinical effectiveness of β-lactams, which remain first-line antibiotics for many infections, is an important part of efforts to address antimicrobial resistance. We report here that inactivation of the predicted d-cycloserine (DCS) transporter gene cycA resensitized methicillin-resistant Staphylococcus aureus (MRSA) to β-lactam antibiotics. The cycA mutation also resulted in hypersusceptibility to DCS, an alanine analogue antibiotic that inhibits alanine racemase and d-alanine ligase required for d-alanine incorporation into cell wall peptidoglycan. Alanine transport was impaired in the cycA mutant, and this correlated with increased susceptibility to oxacillin and DCS. The cycA mutation or exposure to DCS were both associated with the accumulation of muropeptides with tripeptide stems lacking the terminal d-ala-d-ala and reduced peptidoglycan cross-linking, prompting us to investigate synergism between β-lactams and DCS. DCS resensitized MRSA to β-lactams in vitro and significantly enhanced MRSA eradication by oxacillin in a mouse bacteremia model. These findings reveal alanine transport as a new therapeutic target to enhance the susceptibility of MRSA to β-lactam antibiotics.
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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.