ArticleAntimicrobial agents and chemotherapy2011
In vitro selection of variants resistant to beta-lactams plus beta-lactamase inhibitors in CTX-M beta-lactamases: predicting the in vivo scenario?
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 45 citations in OpenAlex.
- Crystal structure of the class A extended-spectrum β-lactamase CTX-M-96 in complex with relebactam at 1.03 Angstrom resolution.Antimicrobial agents and chemotherapy · 2024Article
- Detection by metagenomic functional analysis and improvement by experimental evolution of β-lactams resistance genes present in oil contaminated soils.Scientific reports · 2022Article
- Evolutionary Trajectories toward High-Level β-Lactam/β-Lactamase Inhibitor Resistance in the Presence of Multiple β-Lactamases.Antimicrobial agents and chemotherapy · 2022Article
- Evolutionary Pathways and Trajectories in Antibiotic Resistance.Clinical microbiology reviews · 2021Article
- Antibiotic-Resistant Genes and Bacteria as Evolving Contaminants of Emerging Concerns (e-CEC): Is It Time to Include Evolution in Risk Assessment?Antibiotics (Basel, Switzerland) · 2021Article
- Allogenous Selection of Mutational Collateral Resistance: Old Drugs Select for New Resistance Within Antibiotic Families.Frontiers in microbiology · 2021Review
- Fecal Carriage and Genetic Characterization of CTX-M-1/9/1-ProducingFrontiers in microbiology · 2021Article
- A drug-resistant β-lactamase variant changes the conformation of its active-site proton shuttle to alter substrate specificity and inhibitor potency.The Journal of biological chemistry · 2020Article
- Article
- CTX-M-33, a CTX-M-15 derivative conferring reduced susceptibility to carbapenems.Antimicrobial agents and chemotherapy · 2019Article
- Collateral sensitivity constrains resistance evolution of the CTX-M-15 β-lactamase.Nature communications · 2019Article
- Combination of Amino Acid Substitutions Leading to CTX-M-15-Mediated Resistance to the Ceftazidime-Avibactam Combination.Antimicrobial agents and chemotherapy · 2018Article
- Defining Substrate Specificity in the CTX-M Family: the Role of Asp240 in Ceftazidime Hydrolysis.Antimicrobial agents and chemotherapy · 2018Article
- Genetic and Functional Characterization ofAntimicrobial agents and chemotherapy · 2017Article
- CTX-M-190, a Novel β-Lactamase Resistant to Tazobactam and Sulbactam, Identified in an Escherichia coli Clinical Isolate.Antimicrobial agents and chemotherapy · 2017Article
- A Structure-Based Classification of Class A β-Lactamases, a Broadly Diverse Family of Enzymes.Clinical microbiology reviews · 2016Review
- Escherichia coli β-Lactamases: What Really Matters.Frontiers in microbiology · 2016Review
- Avibactam and inhibitor-resistant SHV β-lactamases.Antimicrobial agents and chemotherapy · 2015Article
- In vitro prediction of the evolution of GES-1 β-lactamase hydrolytic activity.Antimicrobial agents and chemotherapy · 2015Article
- Article
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7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CTX-M β-lactamases are the most prevalent group of enzymes within the extended-spectrum β-lactamases (ESBL). The therapeutic options for CTX-M-carrying isolates are scarce, forcing the reexamination of the therapeutic possibilities of β-lactams plus β-lactamase inhibitors (BBLIs). Inhibitor-resistant CTX-M β-lactamases (IR-CTX-M) have not hitherto been described in natural isolates. In this study, 168 cultures of the hypermutagenic Escherichia coli GB20 strain carrying plasmid pBGS18 with different bla(CTX-M) genes were submitted to parallel experimental evolution assays in the presence of increasing concentrations of a combination of amoxicillin and clavulanate. Fourteen CTX-M β-lactamases belonging to the three most representative clusters (CTX-M-1, -2, and -9) and the two main phenotypes (cefotaxime resistance and cefotaxime-ceftazidime resistance) were studied. Three types of IR-CTX-M mutants were detected, having mutations S130G, K234R, and S237G, which are associated with different resistance patterns. The most frequently recovered mutation was S130G, which conferred the highest resistance levels to BBLIs (reaching 12 μg/ml for amoxicillin-clavulanate and 96 μg/ml for piperacillin-tazobactam when acquired by CTX-M-1 cluster enzymes). The S130G change also provided a clear antagonistic pleiotropy effect, strongly decreasing the enzyme's activity against all cephalosporins tested. A double mutation, S130G L169S, partially restored the resistance against cephalosporins. A complex pattern observed in CTX-M-58, carrying P167S and S130G or K234R changes, conferred ESBL and IR phenotypes simultaneously. The K234R and S237G changes had a smaller effect in providing inhibitor resistance. In summary, IR-CTX-M enzymes might evolve under exposure to BBLIs, and the probability is higher for enzymes belonging to the CTX-M-1 cluster. However, this process could be delayed by antagonistic pleiotropy.
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