ArticleAntimicrobial agents and chemotherapy2015
Complex Regulation Pathways of AmpC-Mediated β-Lactam Resistance in Enterobacter cloacae Complex.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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72 citing papers in PubMed, 101 citations in OpenAlex.
- Population size modulates the transition from gene amplification-mediated heteroresistance to stable resistance.npj antimicrobials and resistance · 2026Article
- Non canonical perspectives on AmpR mediated ampC expression in Gram negative bacteria, with particular emphasis on the potential regulatory purview of FtsZ.World journal of microbiology & biotechnology · 2026Review
- NagX, a periplasmic β-Antimicrobial agents and chemotherapy · 2026Article
- From environmental reservoirs to clinical threats: the expanding resistome and genetic plasticity of Citrobacter spp.Infection · 2026Review
- ComparativeAntimicrobial agents and chemotherapy · 2026Article
- Prevalence and Antimicrobial Resistance Profiles ofAntibiotics (Basel, Switzerland) · 2026Article
- TheInternational journal of molecular sciences · 2026Review
- Genomic analysis ofMicrobial genomics · 2026Article
- Ambler class C-type β-lactamases and porin alterations in Enterobacter cloacae complex and Klebsiella aerogenes in the Netherlands, 2012-2023.BMC microbiology · 2026Article
- Unravelling the triad of penicillin-binding proteins, β-lactamase activity, and mRNA dynamics in Pseudomonas aeruginosa AmpC induction.The Journal of antimicrobial chemotherapy · 2026Article
- Efflux pump overexpression in fluoroquinolone multidrug resistance: molecular mechanisms, PK/PD implications, global epidemiology, and translational strategies.Frontiers in pharmacology · 2026Review
- Exploring heterogeneity in antibiotic choices for bloodstream infections caused by AmpC-producing enterobacterales: results from a case-vignette study.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- Carbapenem-resistant enterobacterales in sterile body fluids: ten-year population genomics and clinical risk factors in a tertiary hospital, 2016-2025.Frontiers in cellular and infection microbiology · 2026Article
- Molecular insights into antimicrobial resistance in human bacterial pathogens: mechanisms, resistance genes, and translational diagnostic applications.Frontiers in microbiology · 2026Review
- Review
- Correlation between the mutation rates for ampC derepression and species or ampC genotypes in Enterobacter cloacae complex.BMC microbiology · 2025Article
- Development of phenotypic and genotypic methods for the identification of NmcA β-lactamases in carbapenem-resistantMicrobiology spectrum · 2025Article
- Unique Regulation of Sed-1 β-Lactamase inAntibiotics (Basel, Switzerland) · 2025Article
- Mutations inMicrobiology spectrum · 2025Article
- Suitability of Piperacillin-Tazobactam for Treating Dogs Infected with Extended-Spectrum β-Lactamase-Producing Enterobacterales: Pharmacokinetic and Pharmacodynamic Analysis.Antibiotics (Basel, Switzerland) · 2025Article
12 more citing papers are in PubMed but not listed here.
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4 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Enterobacter cloacae complex (ECC), an opportunistic pathogen causing numerous infections in hospitalized patients worldwide, is able to resist β-lactams mainly by producing the AmpC β-lactamase enzyme. AmpC expression is highly inducible in the presence of some β-lactams, but the underlying genetic regulation, which is intricately linked to peptidoglycan recycling, is still poorly understood. In this study, we constructed different mutant strains that were affected in genes encoding enzymes suspected to be involved in this pathway. As expected, the inactivation of ampC, ampR (which encodes the regulator protein of ampC), and ampG (encoding a permease) abolished β-lactam resistance. Reverse transcription-quantitative PCR (qRT-PCR) experiments combined with phenotypic studies showed that cefotaxime (at high concentrations) and cefoxitin induced the expression of ampC in different ways: one involving NagZ (a N-acetyl-β-D-glucosaminidase) and another independent of NagZ. Unlike the model established for Pseudomonas aeruginosa, inactivation of DacB (also known as PBP4) was not responsible for a constitutive ampC overexpression in ECC, whereas it caused AmpC-mediated high-level β-lactam resistance, suggesting a post-transcriptional regulation mechanism. Global transcriptomic analysis by transcriptome sequencing (RNA-seq) of a dacB deletion mutant confirmed these results. Lastly, analysis of 37 ECC clinical isolates showed that amino acid changes in the AmpD sequence were likely the most crucial event involved in the development of high-level β-lactam resistance in vivo as opposed to P. aeruginosa where dacB mutations have been commonly found. These findings bring new elements for a better understanding of β-lactam resistance in ECC, which is essential for the identification of novel potential drug targets.
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