Mutation of the maturase lipoprotein attenuates the virulence of Streptococcus equi to a greater extent than does loss of general lipoprotein lipidation
Mutation of the maturase lipoprotein attenuates the virulence of Streptococcus equi to a greater extent than does loss of general lipoprotein lipidation
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DOI：
10.1128/iai.01116-06
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发表时间：
2006-12-01
影响因子：
3.1
通讯作者：
Harrington, Dean J.
中科院分区：
文献类型：
--
作者：
Hamilton, Andrea;Robinson, Carl;Harrington, Dean J.
马链球菌是马的一种流行性高度接触性疾病--马勒颈病的病原体。尽管动物的痛苦和经济负担与扼杀，很少有人知道的分子基础的S。等毒力。在这里，我们研究了一种特殊的脂蛋白和一般的脂蛋白加工途径对S。在体外马的上皮组织中定植，并在体内小鼠模型和天然宿主中引起疾病。在空气界面器官培养物中接种成熟酶脂蛋白缺陷突变株（Delta prtM（138-213），缺失138 - 213个核苷酸）后，其定殖率显著低于感染野生型S.马菌株4047或不能脂化前脂蛋白原的突变菌株（Δ lgt（190-685））。此外，粘液产生在野生型感染和Delta lgt（190-685）感染的器官培养物中均显著更大。在小鼠窒息模型中，与野生型菌株相比，两种突变体均显著减毒，尽管用Delta lgt（190-685）突变体感染的30只小鼠中有2只仍表现出疾病体征。相比之下，在小马感染研究中，仅Delta prtM（138-213）突变体显著减毒，与感染野生型的4只小马中的4只和感染Delta lgt（190-685）突变体的5只小马中的3只相比，5只感染小马中的0只表现出窒息的病理学体征。我们相信，这是第一个研究，以评估的贡献脂蛋白的革兰氏阳性病原体在其自然宿主的毒力。这些数据表明PrtM脂蛋白是一种潜在的疫苗候选物，需要对其活性及其底物进行进一步研究。
Streptococcus equi is the causative agent of strangles, a prevalent and highly contagious disease of horses. Despite the animal suffering and economic burden associated with strangles, little is known about the molecular basis of S. equi virulence. Here we have investigated the contributions of a specific lipoprotein and the general lipoprotein processing pathway to the abilities of S. equi to colonize equine epithelial tissues in vitro and to cause disease in both a mouse model and the natural host in vivo. Colonization of air interface organ cultures after they were inoculated with a mutant strain deficient in the maturase lipoprotein (Delta prtM(138-213), with a deletion of nucleotides 138 to 213) was significantly less than that for cultures infected with wild-type S. equi strain 4047 or a mutant strain that was unable to lipidate preprolipoproteins (Delta lgt(190-685)). Moreover, mucus production was significantly greater in both wild-type-infected and Delta lgt(190-685)-infected organ cultures. Both mutants were significantly attenuated compared with the wild-type strain in a mouse model of strangles, although 2 of 30 mice infected with the Delta lgt(190-685) mutant did still exhibit signs of disease. In contrast, only the Delta prtM(138-213) mutant was significantly attenuated in a pony infection study, with 0 of 5 infected ponies exhibiting pathological signs of strangles compared with 4 of 4 infected with the wild-type and 3 of 5 infected with the Delta lgt(190-685) mutant. We believe that this is the first study to evaluate the contribution of lipoproteins to the virulence of a gram-positive pathogen in its natural host. These data suggest that the PrtM lipoprotein is a potential vaccine candidate, and further investigation of its activity and its substrate(s) are warranted.