Respiratory Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, 30333, Georgia, USA.
Nat Commun. 2019 Jan 14;10(1):178. doi: 10.1038/s41467-018-07997-y.
Bacterial mutations predisposing pneumococcus to causing meningitis, a more severe form of invasive pneumococcal disease (IPD), are largely unknown. Knowledge of such mutations may improve our understanding of pathogenesis and inform preventive strategies. Here we report a pneumococcal pbp1b gene mutation (pbp1bA641C causing N214T change in PBP1b transglycosylase domain) that is associated with meningitis in an exploratory cohort of IPD patients (n = 2054, p = 6.8 × 10), in an independent confirmatory cohort (n = 2518, p = 2.3 × 10), and in a combined analysis (n = 4572, p = 3.0 × 10). Patients infected by the pbp1b641C genotype pneumococci show 2.8-fold odds (95% CI 1.7 to 4.8) of meningitis compared to those infected by non-pbp1b641C pneumococci, after controlling for pneumococcal serotype, antibiotic resistance, and patient age. The pbp1bA641C change results in longer time needed for bacterial killing by antibiotic treatment and shows evidence of being under positive selection. Thus, a pneumococcal mutation conferring increased antibiotic tolerance is associated with meningitis among IPD patients.
导致肺炎球菌易患脑膜炎的细菌突变（一种更严重的侵袭性肺炎球菌病（IPD）形式）在很大程度上尚不清楚。了解此类突变可能有助于我们更好地了解发病机制，并为预防策略提供信息。在这里，我们报告了一种肺炎球菌 pbp1b 基因突变（pbp1bA641C 导致 PBP1b 转糖基酶结构域中的 N214T 变化），该突变与 IPD 患者的探索性队列中的脑膜炎有关（n=2054，p=6.8×10），在独立的确认性队列中（n=2518，p=2.3×10），以及在联合分析中（n=4572，p=3.0×10）。与感染非 pbp1b641C 肺炎球菌的患者相比，感染 pbp1b641C 基因型肺炎球菌的患者发生脑膜炎的几率高 2.8 倍（95%CI1.7 至 4.8），在控制肺炎球菌血清型、抗生素耐药性和患者年龄后。pbp1bA641C 变化导致细菌对抗生素治疗的杀伤时间延长，并显示出正选择的证据。因此，一种赋予抗生素耐药性增加的肺炎球菌突变与 IPD 患者的脑膜炎有关。
