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已发表论文
Ω-环内 Ser165Glu 替换对新型 Ambler A 类β-内酰胺酶变体 LAP-3 水解活性的影响
Authors Lin K, Lü P, Liu Y, Zhou J, Zhou J
Received 31 July 2025
Accepted for publication 8 October 2025
Published 24 October 2025 Volume 2025:18 Pages 5439—5450
DOI https://doi.org/10.2147/IDR.S551859
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Sandip Patil
Kaichun Lin,1 Pan Lü,2 Yining Liu,1 Jingqian Zhou,3 Jian Zhou3
1Department of Otorhinolaryngology, The First People’s Hospital of Yongkang, Jinhua, People’s Republic of China; 2Department of Clinical Laboratory, The First People’s Hospital of Yongkang, Jinhua, People’s Republic of China; 3Department of Pediatrics, The First People’s Hospital of Yongkang, Jinhua, People’s Republic of China
Correspondence: Jian Zhou, Department of Pediatrics, The First People’s Hospital of Yongkang, Jinhua, People’s Republic of China, Email doctzj@126.com
Introduction: Lactamase activity proteins (LAPs) are narrow-spectrum β-lactamases identified within the Enterobacteriaceae family. In this research, we uncovered a novel variant, LAP-3, while investigating quinolone and carbapenem resistance in Klebsiella pneumoniae. Consequently, we aimed to elucidate the hydrolytic profile and to identify and characterize the new β-lactamase, LAP-3.
Methods: Antimicrobial susceptibility was assessed using the agar dilution method. The blaLAP-3 gene was analyzed using PCR, and genomic DNA was extracted for whole-genome sequencing and plasmid mapping. The gene was cloned to analyze the hydrolysis spectrum and biochemical characteristics of LAP-3. Protein structure was analyzed using ChimeraX.
Results: Genome sequencing and BLAST analysis revealed a substitution of glutamic acid (Glu165) with serine (Ser165) in LAP-3 compared to LAP-2 within the Ω-loop. The plasmid sequence containing blaLAP-3 revealed that the gene was situated within the multidrug resistance unit of TnpA-tet(A)-blaLAP-3-qnrS1-TnpR. Structural analysis revealed that Glu165 in LAP-3 formed hydrogen bonds with Glu163 and Asn167, in contrast to Ser165 in LAP-1 and LAP-2. The cloned blaLAP-3 gene resulted in elevated MIC levels for Amoxicillin (64-fold), Piperacillin (64-fold), cefuroxime (16-fold), and Cephalothin (32-fold) and while conferring resistance to clavulanic acid and tazobactam by increasing their MICs 8- and 4-fold, respectively, thereby indicating an expanded resistance spectrum.
Conclusion: The findings reveal that the novel Ambler class A β-lactamase LAP-3 demonstrates an expanded hydrolysis spectrum against Penicillins, certain cephalosporins, and β-lactamase inhibitors. The Ser165Glu substitution within the Ω-loop may influence the resistance characteristics associated with LAP β-lactamases.
Keywords: blaLAP-3, resistance, variant, β-lactamase, Ω-loop
1Department of Otorhinolaryngology, The First People’s Hospital of Yongkang, Jinhua, People’s Republic of China; 2Department of Clinical Laboratory, The First People’s Hospital of Yongkang, Jinhua, People’s Republic of China; 3Department of Pediatrics, The First People’s Hospital of Yongkang, Jinhua, People’s Republic of China
Correspondence: Jian Zhou, Department of Pediatrics, The First People’s Hospital of Yongkang, Jinhua, People’s Republic of China, Email doctzj@126.com
Introduction: Lactamase activity proteins (LAPs) are narrow-spectrum β-lactamases identified within the Enterobacteriaceae family. In this research, we uncovered a novel variant, LAP-3, while investigating quinolone and carbapenem resistance in Klebsiella pneumoniae. Consequently, we aimed to elucidate the hydrolytic profile and to identify and characterize the new β-lactamase, LAP-3.
Methods: Antimicrobial susceptibility was assessed using the agar dilution method. The blaLAP-3 gene was analyzed using PCR, and genomic DNA was extracted for whole-genome sequencing and plasmid mapping. The gene was cloned to analyze the hydrolysis spectrum and biochemical characteristics of LAP-3. Protein structure was analyzed using ChimeraX.
Results: Genome sequencing and BLAST analysis revealed a substitution of glutamic acid (Glu165) with serine (Ser165) in LAP-3 compared to LAP-2 within the Ω-loop. The plasmid sequence containing blaLAP-3 revealed that the gene was situated within the multidrug resistance unit of TnpA-tet(A)-blaLAP-3-qnrS1-TnpR. Structural analysis revealed that Glu165 in LAP-3 formed hydrogen bonds with Glu163 and Asn167, in contrast to Ser165 in LAP-1 and LAP-2. The cloned blaLAP-3 gene resulted in elevated MIC levels for Amoxicillin (64-fold), Piperacillin (64-fold), cefuroxime (16-fold), and Cephalothin (32-fold) and while conferring resistance to clavulanic acid and tazobactam by increasing their MICs 8- and 4-fold, respectively, thereby indicating an expanded resistance spectrum.
Conclusion: The findings reveal that the novel Ambler class A β-lactamase LAP-3 demonstrates an expanded hydrolysis spectrum against Penicillins, certain cephalosporins, and β-lactamase inhibitors. The Ser165Glu substitution within the Ω-loop may influence the resistance characteristics associated with LAP β-lactamases.
Keywords: blaLAP-3, resistance, variant, β-lactamase, Ω-loop