Dynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium.
Dynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium.
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DOI：
10.1038/ncomms10859
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发表时间：
2016-02-29
影响因子：
16.6
通讯作者：
Tuomanen EI
中科院分区：
文献类型：
--
作者：
Kietzman CC;Gao G;Mann B;Myers L;Tuomanen EI
细菌病原体产生复杂的碳水化合物胶囊，以防止杀菌免疫分子。特别是，肺炎球菌荚膜使细菌对上皮表面上发现的抗菌肽敏感。在这里，我们表明，在与抗菌肽相互作用后，包囊肺炎球菌生存的过程中，从细胞表面上的依赖于自杀性酰胺酶自溶素LytA在几分钟内除去胶囊。与经典的细菌自溶相反，在胶囊脱落期间，LytA促进细菌存活并分散在细胞周围。然而，自溶和胶囊脱落都依赖于LytA的细胞壁水解活性。荚膜脱落显著增加上皮细胞的侵袭，是肺炎球菌在小鼠急性肺感染早期减少表面结合荚膜的主要途径。LytA在去除荚膜以对抗抗菌肽中的先前未被认识的作用可以解释为什么尽管抗生素的致命选择压力，但几乎所有的肺炎球菌临床分离株都保留这种酶。 肺炎球菌产生一种碳水化合物胶囊，保护它们免受宿主免疫系统的成分，但使它们对宿主抗菌肽敏感。在此，Kietzman等人表明，肺炎球菌通过荚膜脱落对抗菌肽作出反应，这需要主要的自溶素LytA。
Bacterial pathogens produce complex carbohydrate capsules to protect against bactericidal immune molecules. Paradoxically, the pneumococcal capsule sensitizes the bacterium to antimicrobial peptides found on epithelial surfaces. Here we show that upon interaction with antimicrobial peptides, encapsulated pneumococci survive by removing capsule from the cell surface within minutes in a process dependent on the suicidal amidase autolysin LytA. In contrast to classical bacterial autolysis, during capsule shedding, LytA promotes bacterial survival and is dispersed circumferentially around the cell. However, both autolysis and capsule shedding depend on the cell wall hydrolytic activity of LytA. Capsule shedding drastically increases invasion of epithelial cells and is the main pathway by which pneumococci reduce surface bound capsule during early acute lung infection of mice. The previously unrecognized role of LytA in removing capsule to combat antimicrobial peptides may explain why nearly all clinical isolates of pneumococci conserve this enzyme despite the lethal selective pressure of antibiotics. Pneumococci produce a carbohydrate capsule that protects them against components of the host immune system but sensitizes them to host antimicrobial peptides. Here, Kietzman et al. show that pneumococci respond to antimicrobial peptides by capsule shedding, which requires the main autolysin LytA.