Waz Natalha T, Oliveira Sheila, Girardello Raquel, Lincopan Nilton, Barazzone Giovana, Parisotto Thais, Hakansson Anders P, Converso Thiago Rojas, Darrieux Michelle
Laboratório de Biologia Molecular de Microrganismos, Universidade São Francisco, Bragança Paulista, Brazil.
Laboratório de Resistoma e Alternativas Terapêuticas, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
Front Microbiol. 2022 May 13;13:898815. doi: 10.3389/fmicb.2022.898815. eCollection 2022.
is a pathogen responsible for high morbidity and mortality worldwide. The polysaccharide capsule confers protection against phagocytosis and influences many aspects of pneumococcal pathogenesis. The capsular polysaccharides (CPS) are highly immunogenic and exhibit great structural variability, with more than 100 serotypes described so far. Antimicrobial peptides (AMPs) are an important part of the innate defense mechanisms against many pathogens. Indolicidin is a cationic AMP produced by bovine neutrophils, with bactericidal effects against several bacteria. CPS has been shown to interfere with the ability of AMPs to kill pneumococci, but the effects of capsule variability on susceptibility to indolicidin have not been explored. The present work determined the effects of capsule on resistance to indolicidin . Using a bactericidal plate assay, we observed that different pneumococcal serotypes exhibited variable resistance to indolicidin, which correlated with the capsule net charge. Interestingly, the effect of capsule expression on resistance to indolicidin was dependent on the serotype; bacteria with lower zeta potential were more resistant to indolicidin when capsule was present, while those with less negative surface charge were more resistant in the absence of capsule. The addition of purified CPS partially rescued the bacteria from the bactericidal effects of indolicidin, while the addition of anticapsular antibodies accentuated the peptide's bactericidal action, suggesting a possible new protective mechanism induced by polysaccharide-based pneumococcal vaccines.
是一种在全球范围内导致高发病率和高死亡率的病原体。多糖荚膜赋予其抗吞噬作用，并影响肺炎球菌致病机制的许多方面。荚膜多糖（CPS）具有高度免疫原性，且结构变化很大，迄今为止已描述了100多种血清型。抗菌肽（AMPs）是针对许多病原体的固有防御机制的重要组成部分。吲哚杀菌素是一种由牛中性粒细胞产生的阳离子抗菌肽，对多种细菌具有杀菌作用。已证明CPS会干扰抗菌肽杀死肺炎球菌的能力，但尚未探讨荚膜变异性对吲哚杀菌素敏感性的影响。本研究确定了荚膜对吲哚杀菌素抗性的影响。使用杀菌平板试验，我们观察到不同的肺炎球菌血清型对吲哚杀菌素表现出不同的抗性，这与荚膜净电荷相关。有趣的是，荚膜表达对吲哚杀菌素抗性的影响取决于血清型；当存在荚膜时，ζ电位较低的细菌对吲哚杀菌素更具抗性，而表面电荷负性较小的细菌在无荚膜时更具抗性。添加纯化的CPS可部分使细菌免受吲哚杀菌素的杀菌作用，而添加抗荚膜抗体则会增强该肽的杀菌作用，这表明基于多糖的肺炎球菌疫苗可能诱导了一种新的保护机制。
