β-lactamase
Mechanisms of ResistanceThe Class A Carbapenemases BKC-1 and GPC-1 Both Originate from the Bacterial Genus ShinellaComparative genomics identified the environmental bacterial genus Shinella as the most likely origin of the class A carbapenemases BKC-1 and GPC-1. Available sequences and PCR analyses of additional Shinella species revealed homologous β-lactamases showing up to 85.4% and 93.3% amino acid identity to both enzymes, respectively. The genes conferred resistance to β-lactams once expressed in...
Mechanisms of ResistanceResistance to Ceftazidime/Avibactam plus Meropenem/Vaborbactam When Both Are Used Together Is Achieved in Four Steps in Metallo-β-Lactamase-Negative Klebsiella pneumoniaeSerine β-lactamases are dominant causes of β-lactam resistance in Klebsiella pneumoniae isolates. Recently, this has driven clinical deployment of the β-lactam–β-lactamase inhibitor pairs ceftazidime/avibactam and meropenem/vaborbactam. We show that four steps, i.e., ompK36 and ramR mutation plus carriage of OXA-232 and KPC-3-D178Y variant β-...
Editor's Pick Mechanisms of ResistanceAdding Insult to Injury: Mechanistic Basis for How AmpC Mutations Allow Pseudomonas aeruginosa To Accelerate Cephalosporin Hydrolysis and Evade AvibactamPseudomonas aeruginosa is a leading cause of nosocomial infections worldwide and notorious for its broad-spectrum resistance to antibiotics. A key mechanism that provides extensive resistance to β-lactam antibiotics is the inducible expression of AmpC β-lactamase. Recently, a number of clinical isolates expressing mutated forms of AmpC have been found to be clinically...
Mechanisms of ResistanceProteomic Changes of Klebsiella pneumoniae in Response to Colistin Treatment and crrB Mutation-Mediated Colistin ResistancePolymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant Gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually over the past few years. Although studies on polymyxin mechanisms are expanding, systemwide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how...
Mechanisms of ResistanceRole of Arginine 214 in the Substrate Specificity of OXA-48Increasing numbers of variants of the carbapenem-hydrolyzing class D β-lactamase OXA-48 are identified in Enterobacterales worldwide. Among them, OXA-181 and OXA-232 are of particular interest, as they differ from each other by a single amino acid substitution at position 214 (R in OXA-181 and S in OXA-232) that results in reduced carbapenem-hydrolyzing activity for OXA-232. To investigate the role of amino acid position 214 (...
Editor's Pick Mechanisms of ResistanceInhibition Activity of Avibactam against Nocardia farcinica β-Lactamase FARIFM10152Nocardia farcinica, one of the most frequent pathogenic species responsible for nocardiosis, is characterized by frequent brain involvement and resistance to β-lactams mediated by a class A β-lactamase. Kinetic parameters for hydrolysis of various β-lactams by FARIFM10152 from strain IFM 10152 were determined by spectrophotometry revealing a high catalytic...
Mechanisms of ResistanceRegulation and Anaerobic Function of the Clostridioides difficile β-LactamaseClostridioides difficile causes severe antibiotic-associated diarrhea and colitis. C. difficile is an anaerobic, Gram-positive sporeformer that is highly resistant to β-lactams, the most commonly prescribed antibiotics. The resistance of...
Mechanisms of ResistanceAcquisition of Class C β-Lactamase PAC-1 by Sequence Type 644 Strains of Pseudomonas aeruginosaFour sequence type 664 (ST664) (serotype O:5) strains of Pseudomonas aeruginosa that were highly resistant to antibiotics, including ceftolozane-tazobactam and ceftazidime-avibactam, but were susceptible to colistin were found to harbor the gene encoding the rare class C β-lactamase PAC-1 on a chromosomally located Tn1721-like transposon. The bla...
Mechanisms of ResistanceStructural Insights into the Inhibition of the Extended-Spectrum β-Lactamase PER-2 by AvibactamThe diazabicyclooctane (DBO) avibactam (AVI) reversibly inactivates most serine-β-lactamases.
Mechanisms of ResistanceGenomic Analysis Identifies Novel Pseudomonas aeruginosa Resistance Genes under Selection during Inhaled Aztreonam Therapy In VivoInhaled aztreonam is increasingly used for chronic Pseudomonas aeruginosa suppression in patients with cystic fibrosis (CF), but the potential for that organism to evolve aztreonam resistance remains incompletely explored. Here, we performed genomic analysis of clonally related pre- and posttreatment CF clinical isolate pairs to identify genes that are under positive...