ArticlePLoS pathogens2014
Host-specific enzyme-substrate interactions in SPM-1 metallo-β-lactamase are modulated by second sphere residues.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Biochemical properties and substrate specificity of GOB-38 in Elizabethkingia anophelis.Scientific reports · 2025Article
- Characterization of acquired β-lactamases inMicrobiology spectrum · 2024Article
- In-cell kinetic stability is an essential trait in metallo-β-lactamase evolution.Nature chemical biology · 2023Article
- Metallo-β-lactamases in the Age of Multidrug Resistance: From Structure and Mechanism to Evolution, Dissemination, and Inhibitor Design.Chemical reviews · 2021Review
- Molecular Evolution of Transition Metal Bioavailability at the Host-Pathogen Interface.Trends in microbiology · 2021Review
- Structural and biochemical characterization of the environmental MBLs MYO-1, ECV-1 and SHD-1.The Journal of antimicrobial chemotherapy · 2020Article
- Protein determinants of dissemination and host specificity of metallo-β-lactamases.Nature communications · 2019Article
- Article
- Cyclobutanone Mimics of Intermediates in Metallo-β-Lactamase Catalysis.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
- Shaping Substrate Selectivity in a Broad-Spectrum Metallo-β-Lactamase.Antimicrobial agents and chemotherapy · 2018Article
- Clinical Evolution of New Delhi Metallo-β-Lactamase (NDM) Optimizes Resistance under Zn(II) Deprivation.Antimicrobial agents and chemotherapy · 2018Article
- A general reaction mechanism for carbapenem hydrolysis by mononuclear and binuclear metallo-β-lactamases.Nature communications · 2017Article
- Article
- Insights into an evolutionary strategy leading to antibiotic resistance.Scientific reports · 2017Article
- Crystal Structure of the Metallo-β-Lactamase GOB in the Periplasmic Dizinc Form Reveals an Unusual Metal Site.Antimicrobial agents and chemotherapy · 2016Article
- Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase.Nature chemical biology · 2016Article
- Role of Residues W228 and Y233 in the Structure and Activity of Metallo-β-Lactamase GIM-1.Antimicrobial agents and chemotherapy · 2016Article
- B1-Metallo-β-Lactamases: Where Do We Stand?Current drug targets · 2016Review
- Quantitative Description of a Protein Fitness Landscape Based on Molecular Features.Molecular biology and evolution · 2015Article
- Exploring the Role of Residue 228 in Substrate and Inhibitor Recognition by VIM Metallo-β-lactamases.Biochemistry · 2015Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Pseudomonas aeruginosa is one of the most virulent and resistant non-fermenting Gram-negative pathogens in the clinic. Unfortunately, P. aeruginosa has acquired genes encoding metallo-β-lactamases (MβLs), enzymes able to hydrolyze most β-lactam antibiotics. SPM-1 is an MβL produced only by P. aeruginosa, while other MβLs are found in different bacteria. Despite similar active sites, the resistance profile of MβLs towards β-lactams changes from one enzyme to the other. SPM-1 is unique among pathogen-associated MβLs in that it contains "atypical" second sphere residues (S84, G121). Codon randomization on these positions and further selection of resistance-conferring mutants was performed. MICs, periplasmic enzymatic activity, Zn(II) requirements, and protein stability was assessed. Our results indicated that identity of second sphere residues modulates the substrate preferences and the resistance profile of SPM-1 expressed in P. aeruginosa. The second sphere residues found in wild type SPM-1 give rise to a substrate selectivity that is observed only in the periplasmic environment. These residues also allow SPM-1 to confer resistance in P. aeruginosa under Zn(II)-limiting conditions, such as those expected under infection. By optimizing the catalytic efficiency towards β-lactam antibiotics, the enzyme stability and the Zn(II) binding features, molecular evolution meets the specific needs of a pathogenic bacterial host by means of substitutions outside the active site.
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