ArticleThe Journal of biological chemistry2009
Mechanistic basis for the emergence of catalytic competence against carbapenem antibiotics by the GES family of beta-lactamases.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Structural basis for carbapenem-hydrolyzing mechanisms of carbapenemases conferring antibiotic resistance.International journal of molecular sciences · 2015Pooled it
- Evaluation of carbapenem inactivation method-based phenotypic assays for the detection of GES-type carbapenemases in Enterobacterales,Journal of clinical microbiology · 2026Article
- Dual mechanism of the OXA-23 carbapenemase inhibition by the carbapenem NA-1-157.Antimicrobial agents and chemotherapy · 2025Article
- Article
- Challenges in laboratory diagnosis and antibiotic treatment options for a newly described Pseudomonas aeruginosa class A beta-lactamase type GES-62 strain.GMS infectious diseases · 2025Article
- Restricted Rotational Flexibility of the C5α-Methyl-Substituted Carbapenem NA-1-157 Leads to Potent Inhibition of the GES-5 Carbapenemase.ACS infectious diseases · 2024Article
- Resistance inAntibiotics (Basel, Switzerland) · 2023Review
- Whole-Genome Sequencing-Based Resistome Analysis of Nosocomial Multidrug-Resistant Non-Fermenting Gram-Negative Pathogens from the Balkans.Microorganisms · 2023Review
- Article
- Article
- Mechanistic Basis of OXA-48-like β-Lactamases' Hydrolysis of Carbapenems.ACS infectious diseases · 2021Article
- Mobile Carbapenemase Genes inFrontiers in microbiology · 2021Review
- 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
- A surface loop modulates activity of the Bacillus class D β-lactamases.Journal of structural biology · 2020Article
- Evaluation of the EDTA-Modified Carbapenem Inactivation Method for Detecting Metallo-β-Lactamase-ProducingJournal of clinical microbiology · 2020Article
- Biocatalytic production of bicyclic β-lactams with three contiguous chiral centres using engineered crotonases.Communications chemistry · 2019Article
- Interplay between β-lactamases and new β-lactamase inhibitors.Nature reviews. Microbiology · 2019Review
- Evaluation of a Modified Carbapenem Inactivation Method for Detection of Carbapenemases in Pseudomonas aeruginosa.Journal of clinical microbiology · 2018Article
- The role of conserved surface hydrophobic residues in the carbapenemase activity of the class D β-lactamases.Acta crystallographica. Section D, Structural biology · 2017Article
- Clonal Dissemination of Pseudomonas aeruginosa Sequence Type 235 Isolates Carrying blaIMP-6 and Emergence of blaGES-24 and blaIMP-10 on Novel Genomic Islands PAGI-15 and -16 in South Korea.Antimicrobial agents and chemotherapy · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
A major mechanism of bacterial resistance to beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, etc.) is the production of beta-lactamases. A handful of class A beta-lactamases have been discovered that have acquired the ability to turn over carbapenem antibiotics. This is a disconcerting development, as carbapenems are often considered last resort antibiotics in the treatment of difficult infections. The GES family of beta-lactamases constitutes a group of extended spectrum resistance enzymes that hydrolyze penicillins and cephalosporins avidly. A single amino acid substitution at position 170 has expanded the breadth of activity to include carbapenems. The basis for this expansion of activity is investigated in this first report of detailed steady-state and pre-steady-state kinetics of carbapenem hydrolysis, performed with a class A carbapenemase. Monitoring the turnover of imipenem (a carbapenem) by GES-1 (Gly-170) revealed the acylation step as rate-limiting. GES-2 (Asn-170) has an enhanced rate of acylation, compared with GES-1, and no longer has a single rate-determining step. Both the acylation and deacylation steps are of equal magnitude. GES-5 (Ser-170) exhibits an enhancement of the rate constant for acylation by a remarkable 5000-fold, whereby the enzyme acylation event is no longer rate-limiting. This carbapenemase exhibits k(cat)/K(m) of 3 x 10(5) m(-1)s(-1), which is sufficient for manifestation of resistance against imipenem.
Indexed as
Identifiers
What OpenQuestion holds
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.