Ribes Sandra, Abdullah Mohammed R, Saleh Malek, Hanisch Uwe-Karsten, Nau Roland, Hammerschmidt Sven
Institute of Neuropathology, University Medical Center Göttingen.
Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, Germany.
J Infect Dis. 2016 Sep 15;214(6):953-61. doi: 10.1093/infdis/jiw268. Epub 2016 Jul 1.
Pneumococcal proteins involved in the resistance against oxidative stress are present in all strains and therefore are potential antigens that could be suitable for new therapies and/or vaccines. Their role in the pathogenesis of pneumococcal meningitis has not been addressed.
We investigated the individual contributions of extracellular thioredoxin lipoproteins (Etrx1 and Etrx2) and the intracellular and extracellular methionine sulfoxide reductases (SpMsrAB1 and SpMsrAB2, respectively) in the progression and outcome of pneumococcal meningitis, using Kaplan-Meier survival curves, bacteriological and histological studies, and measurements of proinflammatory mediators.
The absence of Etrx1, Etrx2, or SpMsrAB1 moderately attenuated virulence as compared to the wild-type strain but did not significantly affect bacterial growth in the brain and bloodstream. Loss of function of SpMsrAB2 alone, both Etrx proteins, or both SpMsrAB proteins resulted in a less severe course of infection, with low numbers of animals dying of infection, a lower risk of associated meningeal inflammation, and reduced bacterial densities in the cerebellum, blood, and spleen.
Our data support the importance of the extracellular redox repair system in virulence and its potential as a target for the design of new antimicrobials and vaccine formulations against Streptococcus pneumoniae.
参与抵抗氧化应激的肺炎球菌蛋白存在于所有菌株中，因此是可能适用于新疗法和/或疫苗的潜在抗原。它们在肺炎球菌性脑膜炎发病机制中的作用尚未得到研究。
我们使用Kaplan-Meier生存曲线、细菌学和组织学研究以及促炎介质测量，研究了细胞外硫氧还蛋白脂蛋白（Etrx1和Etrx2）以及细胞内和细胞外甲硫氨酸亚砜还原酶（分别为SpMsrAB1和SpMsrAB2）在肺炎球菌性脑膜炎进展和结局中的个体作用。
与野生型菌株相比，Etrx1、Etrx2或SpMsrAB1的缺失适度减弱了毒力，但对大脑和血液中的细菌生长没有显著影响。单独缺失SpMsrAB2、两种Etrx蛋白或两种SpMsrAB蛋白导致感染过程较轻，死于感染的动物数量较少，相关脑膜炎症的风险较低，并且小脑、血液和脾脏中的细菌密度降低。
我们的数据支持细胞外氧化还原修复系统在毒力中的重要性及其作为设计针对肺炎链球菌的新型抗菌药物和疫苗制剂靶点的潜力。
