ArticleAnnals of clinical microbiology and antimicrobials2023
Resistance to aztreonam-avibactam due to a mutation of SHV-12 in Enterobacter.
Article in Annals of clinical microbiology and antimicrobials, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Breaking the deadlock of metallo-β-lactamases: evidence and prospects for Aztreonam/Avibactam.Emerging microbes & infections · 2026Review
- Comparison of agar-based methodologies to broth disc elution for the detection of aztreonam susceptibility in the presence of ceftazidime-avibactam.Microbiology spectrum · 2026Article
- Comparative analysis of the effects of aztreonam combined with four β-lactamase inhibitors against carbapenem-resistantMicrobiology spectrum · 2026Article
- Genomic epidemiology and aztreonam-avibactam resistance mechanisms of Proteus mirabilis in china: an eight-year retrospective study.Annals of clinical microbiology and antimicrobials · 2026Article
- Epidemiology of ESBL-Producing, Carbapenem-Resistant, and Carbapenemase-Producing Enterobacterales in Southern Africa.Antibiotics (Basel, Switzerland) · 2026Review
- Whole-genome analysis of NDM-producingEmerging microbes & infections · 2025Article
- Effect of Mutations on the Evolution of Extended Spectrum β-lactamases (ESBL).The protein journal · 2025Review
- Aztreonam/avibactam activity against Enterobacterales from European medical centres: summary of 5 years of surveillance prior to approval for clinical use (2019-2023).The Journal of antimicrobial chemotherapy · 2025Article
- Molecular resistance mechanisms to newly approved antibiotics (2017-2025) in WHO priority pathogens.Frontiers in microbiology · 2025Review
- Aztreonam-avibactam: The dynamic duo against multidrug-resistant gram-negative pathogens.Pharmacotherapy · 2024Review
- Practical Application of Aztreonam-Avibactam as a Treatment Strategy for Ambler Class B Metallo-β-Lactamase Producing Enterobacteriaceae.Antibiotics (Basel, Switzerland) · 2024Review
- In Vitro Susceptibility of Aztreonam-Vaborbactam, Aztreonam-Relebactam and Aztreonam-Avibactam Associations against Metallo-β-Lactamase-Producing Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Aztreonam-avibactam is an important option against Enterobacterales producing metallo-β-lactamases (MBLs). We obtained an aztreonam-avibactam-resistant mutant of an MBL-producing Enterobacter mori strain by induced mutagenesis. Genome sequencing revealed an Arg244Gly (Ambler position) substitution of SHV-12 β-lactamase in the mutant. Cloning and susceptibility testing verified that the SHV-12 Arg244Gly substitution led to significantly reduced susceptibility to aztreonam-avibactam (MIC, from 0.5/4 to 4/4 mg/L) but with the loss of resistance to cephalosporins as tradeoff. Arg244 of SHV involves in the binding of avibactam by forming an arginine-mediated salt bridge and is a critical residue to interact with β-lactams. Molecular modeling analysis demonstrated that the Arg244Gly substitution hindered the binding of avibactam to SHV with higher binding energy (from - 5.24 to -4.32 kcal/mol) and elevated inhibition constant Ki (from 143.96 to 677.37 µM) to indicate lower affinity. This substitution, however, resulted in loss of resistance to cephalosporins as tradeoff by impairing substrate binding. This represents a new aztreonam-avibactam resistance mechanism.
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