Comparative subproteome analysis of three representative Leptospira interrogans vaccine strains reveals cross-reactive antigens and novel virulence determinants
Comparative subproteome analysis of three representative Leptospira interrogans vaccine strains reveals cross-reactive antigens and novel virulence determinants
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三种代表性问号钩端螺旋体疫苗株的比较亚蛋白质组分析揭示了交叉反应抗原和新的毒力决定簇
DOI：
10.1016/j.jprot.2014.08.015
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发表时间：
2015
影响因子：
3.3
通讯作者：
Zhu Yong-Zhang
中科院分区：
文献类型：
--
作者：
Zeng Ling-Bing;Zhuang Xu-Ran;Huang Li-Li;Zhang Yun-Yi;Chen Chun-Yan;Dong Ke;Zhang Yan;Cui Ze-Lin;Ding Xia-Li;Chang Yung-Fu;Guo Xiao-Kui;Zhu Yong-Zhang
致病性钩端螺旋体在中国和全世界引起钩端螺旋体病。本文对我国目前使用的犬型和七日型两株问号军团菌强毒疫苗株JDL 03和JDL 10进行了序列测定。我们选择了一个亚蛋白质组学的方法来确定表面暴露的蛋白质，包括外膜蛋白和胞外蛋白的这两个菌株加上一个高毒力的疫苗株56601（血清型赖）。3个菌株的表面暴露蛋白质组比较表明，81个核心，61个重复和122个独特的表面暴露蛋白。最后，10个高度保守的表面暴露或亚表面蛋白包括两个已知的交叉反应抗原（LipL 32和LA_3469）和另外两个新的抗原（LA_0136和LA_0505）显示15个中国流行血清型中的保守免疫反应性。此外，在这些鉴定的表面暴露蛋白中检测到许多潜在的毒力因子，例如Loa 22、LipL 32、LenC、LenF和OmpL 37。有趣的是，LipL 45、ClpA和ClpB具有明显的氨基酸突变str.56601、str.JDL03和JDL 10，这可能有助于观察到这些菌株之间的毒力差异。此外，问号钩端螺旋体56601中的特异性表面暴露蛋白被认为是关键的毒力决定因子，如锌依赖蛋白酶、胆固醇氧化酶前体等。这将提高我们对钩端螺旋体致病机制和关键毒力决定因素的理解。生物学意义亚蛋白质组学研究，用于鉴定针对钩端螺旋体病的潜在疫苗和诊断抗原候选物。这些数据表明，保守的表面暴露的蛋白质是新的潜在的疫苗/诊断候选人。此外，数据还显示，来自这三个菌株的LipL 45、ClpA、ClpB和脂蛋白加上另一个高毒力菌株Fiocruz L1-130在菌株JDL 03和JDL 10中含有特定的氨基酸突变。致病性问号钩端螺旋体表面暴露的亚蛋白质组为更全面地了解钩端螺旋体的致病性和毒力决定因素提供了有价值的信息。
PathogenicLeptospiraspp. causes leptospirosis in China and throughout the world. Here, we have sequenced twoL.interrogansmoderately virulent vaccine strains JDL03 (serovar Canicola) and JDL10 (serovar Hebdomadis) used in China. We selected a subproteomic approach to identify surface-exposed proteins including OMPs and extracellular proteins of these two strains plus a highly virulent vaccine strain 56601 (serovar Lai). Comparative surface-exposed proteome among the three strains indicated 81 cores, 61 dispensable and 122 unique surface-exposed proteins. Finally, the 10 highly conserved surface-exposed or subsurface proteins included two known cross-reactive antigens (LipL32 and LA_3469) and another two novel antigens (LA_0136 and LA_0505) displaying conserved immunoreactivity among 15 Chinese epidemic serovars. Furthermore, many potential virulence factors were detected in these identified surface-exposed proteins, such as Loa22, LipL32, LenC, LenF and OmpL37. Interestingly, LipL45, ClpA and ClpB, exhibiting obvious amino acid mutations amongstr.56601,str.JDL03 and JDL10, might contribute to virulence differences observed among these strains. Additionally, specific surface-exposed proteins in virulentstr.56601 were considered to be key virulence determinants, such as Zn-dependent protease, cholesterol oxidase precursor, and so on. In all, we had relatively complete surface-exposed subproteomes ofL.interrogans, which will enhance our understanding of leptospiral pathogenesis and key virulence determinants.Biological significanceThe present work demonstrates the use of genomic sequencing and subproteomic studies for the identification of potential vaccine and diagnostic antigen candidates against leptospirosis. The data show the conserved surface-exposed proteins to be novel potentially vaccine/diagnostic candidates. Furthermore, the data also show that LipL45, ClpA, ClpB and a lipoprotein from these three strains plus another highly virulent strain Fiocruz L1-130 contain specific amino acid mutations in strains JDL03 and JDL10. The surface-exposed subproteome of pathogenicL.interroganscould provide valuable information to gain a more complete understanding of leptospiral pathogenesis and virulence determinants.