Affinity of cefditoren for penicillin-binding proteins in bacteria and its relationship with antibiotic sensitivity.

Autor: Qi Y; School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, Jiangsu, China., Shi Q; School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, Jiangsu, China., Ma L; School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, Jiangsu, China., Xu L; Nanjing Neiwa Faith Pharmaceutical Co Ltd., No. 36, Shuanggao Road, Nanjing, 211399, Jiangsu, China., Deng Y; Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, No.1617, Riyue Avenue, Qinyang District, Chengdu, 611731, China. dengyi@wcch.cn., Zhou C; School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, Jiangsu, China. cl_zhou@cpu.edu.cn.
Jazyk: angličtina
Zdroj: Archives of microbiology [Arch Microbiol] 2024 Nov 18; Vol. 206 (12), pp. 469. Date of Electronic Publication: 2024 Nov 18.
DOI: 10.1007/s00203-024-04194-y
Abstrakt: Penicillin-binding proteins (PBPs) are the targets of β-lactam antibiotics; however, changes in the affinity of PBPs for beta-lactam antibiotics often affect the susceptibility of bacteria to antibiotics. The purpose of this study was to elucidate the mechanism by which cefditoren, an oral third-generation cephalosporin, binds PBPs. The minimal inhibitory concentration (MIC), bactericidal curves, and inhibition zone comparisons were assessed to evaluate the antibacterial activity of cefditoren. PBP1A and PBP2X proteins from Streptococcus pneumoniae were purified, and their ability to bind to cefditoren was investigated via microscale thermophoresis. The Kd of cefditoren toward PBP1A was 0.005 ± 0.004 µM, which was lower than those of other cephalosporins (cefcapene, cefixime and cefdinir). In contrast, the Kd of cefditoren toward PBP2X of S. pneumoniae was 9.70 ± 8.24 µM, which was lower than that of cefixime but higher than those of cefcapene and cefdinir. Additionally, the biotinylated ampicillin (BIO-AMP) method was employed to evaluate the affinity of cefditoren toward PBPs of Haemophilus influenzae, and the results demonstrated that cefditoren and PBP3A/B had the lowest IC 50 values (0.060 ± 0.002 µM). These findings indicate that cefditoren has a strong affinity for PBP1A of H. influenzae. Cefditoren has a high affinity toward the PBP1As of S. pneumoniae and PBP1A and PBP3A/B of H. influenzae, which may contribute to the effective antibacterial effects of cefditoren against clinical strains and its low propensity for inducing resistance. The data presented in this article help elucidate the mechanism by which cefditoren, an oral third-generation cephalosporin, binds to PBPs and provide theoretical support for the wider use of cefditoren as an antibiotic therapy.
Competing Interests: Declarations Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: