دورية أكاديمية
Natural protein engineering in the Ω-loop: the role of Y221 in ceftazidime and ceftolozane resistance in Pseudomonas -derived cephalosporinase.
العنوان: | Natural protein engineering in the Ω-loop: the role of Y221 in ceftazidime and ceftolozane resistance in Pseudomonas -derived cephalosporinase. |
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المؤلفون: | Mack AR; Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA.; Research Service, VA Northeast Ohio Healthcare System , Cleveland, Ohio, USA., Kumar V; Department of Biochemistry, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA., Taracila MA; Research Service, VA Northeast Ohio Healthcare System , Cleveland, Ohio, USA.; Department of Medicine, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA., Mojica MF; Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA.; Research Service, VA Northeast Ohio Healthcare System , Cleveland, Ohio, USA.; CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES) , Cleveland, Ohio, USA., O'Shea M; Research Service, VA Northeast Ohio Healthcare System , Cleveland, Ohio, USA., Schinabeck W; Research Service, VA Northeast Ohio Healthcare System , Cleveland, Ohio, USA., Silver G; Research Service, VA Northeast Ohio Healthcare System , Cleveland, Ohio, USA., Hujer AM; Research Service, VA Northeast Ohio Healthcare System , Cleveland, Ohio, USA.; Department of Medicine, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA., Papp-Wallace KM; Research Service, VA Northeast Ohio Healthcare System , Cleveland, Ohio, USA.; Department of Biochemistry, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA.; Department of Medicine, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA., Chen S; Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University College London , London, England, United Kingdom., Haider S; Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University College London , London, England, United Kingdom.; UCL Centre for Advanced Research Computing, University College London , London, England, United Kingdom., Caselli E; Department of Life Sciences, University of Modena and Reggio Emilia , Modena, Italy., Prati F; Department of Life Sciences, University of Modena and Reggio Emilia , Modena, Italy., van den Akker F; Department of Biochemistry, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA., Bonomo RA; Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA.; Department of Biochemistry, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA.; Department of Medicine, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA.; CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES) , Cleveland, Ohio, USA.; Department of Pharmacology, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA.; Department of Proteomics and Bioinformatics, Case Western Reserve University School of Medicine , Cleveland, Ohio, USA.; Clinician Scientist Investigator, Louis Stokes Cleveland Department of Veterans Affairs Medical Center , Cleveland, Ohio, USA. |
المصدر: | Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2023 Nov 15; Vol. 67 (11), pp. e0079123. Date of Electronic Publication: 2023 Oct 18. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 0315061 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-6596 (Electronic) Linking ISSN: 00664804 NLM ISO Abbreviation: Antimicrob Agents Chemother Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, American Society for Microbiology |
مواضيع طبية MeSH: | Ceftazidime*/pharmacology , Cephalosporinase*/metabolism, Pseudomonas/genetics ; Molecular Docking Simulation ; beta-Lactamases/metabolism ; Protein Engineering ; Microbial Sensitivity Tests ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/metabolism ; Azabicyclo Compounds/pharmacology ; Pseudomonas aeruginosa/metabolism ; Drug Combinations |
مستخلص: | A wide variety of clinically observed single amino acid substitutions in the Ω-loop region have been associated with increased minimum inhibitory concentrations and resistance to ceftazidime (CAZ) and ceftolozane (TOL) in Pseudomonas -derived cephalosporinase and other class C β-lactamases. Herein, we demonstrate the naturally occurring tyrosine to histidine substitution of amino acid 221 (Y221H) in Pseudomonas -derived cephalosporinase (PDC) enables CAZ and TOL hydrolysis, leading to similar kinetic profiles ( k Competing Interests: The authors declare no conflict of interest. |
معلومات مُعتمدة: | R01 AI063517 United States AI NIAID NIH HHS |
فهرسة مساهمة: | Keywords: Pseudomonas aeruginosa; Pseudomonas-derived cephalosporinase (PDC); Y221H; antibiotic resistance; beta-lactamases; beta-lactmase inhibitor; boronic acid transition state inhibitor (BATSI); ceftazidime resistance; ceftolozane resistance; enzyme kinetics |
المشرفين على المادة: | 9M416Z9QNR (Ceftazidime) 37A4IES95Q (ceftolozane) EC 3.5.2.- (Cephalosporinase) 0 (S02030) EC 3.5.2.6 (beta-Lactamases) 0 (Anti-Bacterial Agents) 0 (Azabicyclo Compounds) 0 (Drug Combinations) |
تواريخ الأحداث: | Date Created: 20231018 Date Completed: 20231216 Latest Revision: 20240210 |
رمز التحديث: | 20240210 |
مُعرف محوري في PubMed: | PMC10648885 |
DOI: | 10.1128/aac.00791-23 |
PMID: | 37850746 |
قاعدة البيانات: | MEDLINE |
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