ArticleAntimicrobial agents and chemotherapy2013
Can inhibitor-resistant substitutions in the Mycobacterium tuberculosis β-Lactamase BlaC lead to clavulanate resistance?: a biochemical rationale for the use of β-lactam-β-lactamase inhibitor combinations.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 45 citations in OpenAlex.
- Strategic design of a multi-tier database for class A β-lactamase BlaC variants of M. tuberculosis: advancing the fight against antibacterial resistance.The Journal of antibiotics · 2025Article
- Phosphate ions modulate enzyme activity and epistatic effects in two clavulanic acid-resistant β-lactamase mutants.Protein science : a publication of the Protein Society · 2025Article
- Comparative evaluation of five β-Lactamase inhibitors in combination with β-Lactams against multidrug-resistant Mycobacterium tuberculosis in vitro.BMC infectious diseases · 2025Article
- Article
- Positive epistasis drives clavulanic acid resistance in double mutant libraries of BlaC β-lactamase.Communications biology · 2024Article
- Mycobacterium tuberculosis β-lactamase variant reduces sensitivity to ampicillin/avibactam in a zebrafish-Mycobacterium marinum model of tuberculosis.Scientific reports · 2023Article
- Characterization of a Class A β-Lactamase fromACS bio & med chem Au · 2023Article
- Are the Newer Carbapenems of Any Value against Tuberculosis.Antibiotics (Basel, Switzerland) · 2022Article
- Susceptibility of β-Lactam Antibiotics and Genetic Mutation of Drug-Resistant Mycobacterium tuberculosis Isolates in Korea.Tuberculosis and respiratory diseases · 2022Article
- The G132S Mutation Enhances the Resistance ofBiochemistry · 2021Article
- Two β-Lactamase Variants with Reduced Clavulanic Acid Inhibition Display Different Millisecond Dynamics.Antimicrobial agents and chemotherapy · 2021Article
- Variations in the SDN Loop of Class A Beta-Lactamases: A Study of the Molecular Mechanism of BlaC (Frontiers in microbiology · 2021Article
- Repurposing Immunomodulatory Drugs to Combat Tuberculosis.Frontiers in immunology · 2021Review
- Bis(benzoyl) phosphate inactivators of beta-lactamase C from Mtb.Bioorganic & medicinal chemistry letters · 2019Article
- Crystal Structure of Phosphoserine BlaC fromInternational journal of molecular sciences · 2019Article
- Evaluation of Carbapenems for Treatment of Multi- and Extensively Drug-ResistantAntimicrobial agents and chemotherapy · 2019Article
- Peptidoglycan in Mycobacteria: chemistry, biology and intervention.Glycoconjugate journal · 2018Review
- Identification of differentially expressed microRNAs in Sahiwal (Bos indicus) breed of cattle during thermal stress.Cell stress & chaperones · 2018Article
- Phosphate Promotes the Recovery of Mycobacterium tuberculosis β-Lactamase from Clavulanic Acid Inhibition.Biochemistry · 2017Article
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
The current emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis calls for novel treatment strategies. Recently, BlaC, the principal β-lactamase of Mycobacterium tuberculosis, was recognized as a potential therapeutic target. The combination of meropenem and clavulanic acid, which inhibits BlaC, was found to be effective against even extensively drug-resistant M. tuberculosis strains when tested in vitro. Yet there is significant concern that drug resistance against this combination will also emerge. To investigate the potential of BlaC to evolve variants resistant to clavulanic acid, we introduced substitutions at important amino acid residues of M. tuberculosis BlaC (R220, A244, S130, and T237). Whereas the substitutions clearly led to in vitro clavulanic acid resistance in enzymatic assays but at the expense of catalytic activity, transformation of variant BlaCs into an M. tuberculosis H37Rv background revealed that impaired inhibition of BlaC did not affect inhibition of growth in the presence of ampicillin and clavulanate. From these data we propose that resistance to β-lactam-β-lactamase inhibitor combinations will likely not arise from structural alteration of BlaC, therefore establishing confidence that this therapeutic modality can be part of a successful treatment regimen against M. tuberculosis.
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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.