863课题—兽药微生物功能基因组学最终报告

贝为成

摘 要：该研究以自行分离鉴定的我国流行猪链球菌和副猪嗜血杆菌菌株为发菌株，开展了副猪嗜血杆菌和猪链球菌全基因组测序和分析、重要功能新基因发掘、新药靶标筛选及新药先导化合物筛选等研究。目前已经完成9株副猪嗜血杆菌、8猪链球菌全基因组测序、分析和注释；通过基因组学、比较基因组学、转录助学、蛋白质组学、代谢组学等技术发掘了16个重要功能新基因，通过基因克隆、表达、敲除等技术，证实了它们与副猪嗜血杆菌或猪链球菌毒力、免疫原性、生长、代谢、调控等功能相关相关。其中猪链球菌HP0197、S0153、1358hk、GlnA、HMRG、副猪嗜血杆菌lon等6个基因白缺失后细菌完全不致病或细菌不能生长，是潜在的药物靶标和重要毒力因子。副猪嗜血杆菌PalA，Omp2，D15，HPS_06257、HPS_2063、HPS_0687、OAPA等7个基因是重要免疫原性基因。鉴定了猪链球菌SSP、IgA、副猪嗜血杆菌等3个重要毒力因子。进一步对可能的新药靶标进行了研究，初步获得了1358hk、HMRG 2个新药靶标结构和先导化合物抑制剂。

关键词：猪链球菌 副猪嗜血杆菌 新药靶标

Abstract：In this study， the genome sequencing and analysis， exploration of important genes， screening of new drug targets and lead compounds for new drugs are carried out based on the domestic popular strains of Streptococcus suis and Haemophilus parasuis we separated and characterized. At present， we have finished the genome sequencing， analysis and annotation of 9 Haemophilus parasuis strains and 8 Streptococcus suis strains. Sixteen new and important genes are explored with genomics， comparative genomics， transcriptomics， proteomics， and metabolomics techniques.these new and important genes were confirmed to be related to virulence， immunogenicity， growth， metabolism， regulation and other functions by cloning， expressing and mutation technology. Bacteria completely lose pathogenicity or can not grow while HP0197 S0153、1358hk、GlnA、 HMRG of Streptococcus suis or lon of Haemophilus parasuis is deleted. Consequently， they are potent drug targets and important virulence factors. It was also demonstrated that PalA， Omp2， D15，HPS_06257、HPS_2063、HPS_0687、OAPA of Haemophilus parasuis are important immunogenic genes. Besides， SSP and IgA of Streptococcus suis and SodA of Haemophilus parasuis are identified as important virulence factors. Further study of potential drug targets are carried out， and the structure and lead compound inhibitors of 1358hk， HMRG 2 are obtained.

Key Words：Streptococcus Suis； Haemophilus Parasuis；Novel Drug Targets

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