Li Lu, Wan Yushun, Wang Yuncheng, Tao Ye, Long Xiao, Liu Enmei, Deng Yu
Department of Respiratory Medicine, National Clinical Research for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Key Laboratory of Children's Important Organ Development and Diseases of Chongqing Municipal Health Commission, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
College of Basic Medicine of Chongqing Medical University, 1 Yixueyuan Road Yuzhong District, Chongqing, 400014, China.
BMC Microbiol. 2025 Jun 9;25(1):363. doi: 10.1186/s12866-025-04066-5.
This study characterizes the molecular interplay between respiratory syncytial virus (RSV) glycoproteins (G/F) and Streptococcus pneumoniae (S.pn) penicillin-binding proteins (PBPs), while evaluating RSV's potential role in modulating S.pn β-lactam resistance.
Protein docking and pull-down assays assessed G/F-PBP interactions. In vitro RSV-S.pn co-culture experiments evaluated β-lactam susceptibility (MIC determination). We retrospectively analyzed 2012-2021 antimicrobial resistance data from 1-59-month-old community-acquired pneumonia patients at Chongqing Medical University Children's Hospital with confirmed S.pn and/or RSV nasopharyngeal carriage.
Computational modeling revealed low G/F-PBP binding affinity (iPTM < 0.6), corroborated by absent PBP1a interaction in pull-down assays. RSV exposure did not alter S.pn β-lactam MICs (penicillin/amoxicillin ≤ 2 µg/mL; cefepime/cefotaxime ≤ 1 µg/mL; meropenem ≤ 0.25 µg/mL). Retrospective data showed elevated penicillin resistance in RSV + S.pn co-detections vs. S.pn alone during 2012 (2.8% vs. 40.9%), 2017 (2.8% vs. 30.4%), and 2018 (6.2% vs. 38.6%) (all p < 0.001). No RSV-associated resistance increases occurred for amoxicillin, cephalosporins, or meropenem.
RSV demonstrates negligible impact on S.pn β-lactam resistance mechanisms, elevated resistance rates to amoxicillin and cephalosporins necessitate enhanced antimicrobial stewardship through diagnostic-guided prescribing and resistance surveillance to optimize β-lactam efficacy in pediatric care.
本研究描述了呼吸道合胞病毒（RSV）糖蛋白（G/F）与肺炎链球菌（S.pn）青霉素结合蛋白（PBPs）之间的分子相互作用，同时评估RSV在调节S.pnβ-内酰胺耐药性方面的潜在作用。
蛋白质对接和下拉实验评估G/F与PBP的相互作用。体外RSV-S.pn共培养实验评估β-内酰胺敏感性（MIC测定）。我们回顾性分析了重庆医科大学附属儿童医院2012年至2021年1至五岁9个月社区获得性肺炎患者的抗菌药物耐药数据，这些患者确诊为S.pn和/或RSV鼻咽携带。
计算模型显示G/F与PBP的结合亲和力较低（iPTM＜0.6），下拉实验中PBP1a无相互作用证实了这一点。RSV暴露未改变S.pn的β-内酰胺MIC（青霉素/阿莫西林≤2μg/mL；头孢吡肟/头孢噻肟≤1μg/mL；美罗培南≤0.25μg/mL）。回顾性数据显示，2012年（2.8%对40.9%）、2017年（2.8%对30.4%）和2018年（6.2%对38.6%），RSV+S.pn联合检测中的青霉素耐药率高于单独检测S.pn（所有p＜0.001）。阿莫西林、头孢菌素或美罗培南未出现与RSV相关的耐药性增加。
RSV对S.pnβ-内酰胺耐药机制的影响可忽略不计，阿莫西林和头孢菌素耐药率升高，需要通过诊断指导用药和耐药监测加强抗菌药物管理，以优化儿科护理中β-内酰胺的疗效。
