863課題—獸藥微生物功能基因組學最終報告

貝為成

摘 要：該研究以自行分離鑒定的我國流行豬鏈球菌和副豬嗜血桿菌菌株為發菌株，開展了副豬嗜血桿菌和豬鏈球菌全基因組測序和分析、重要功能新基因發掘、新藥靶標篩選及新藥先導化合物篩選等研究。目前已經完成9株副豬嗜血桿菌、8豬鏈球菌全基因組測序、分析和注釋；通過基因組學、比較基因組學、轉錄助學、蛋白質組學、代謝組學等技術發掘了16個重要功能新基因，通過基因克隆、表達、敲除等技術，證實了它們與副豬嗜血桿菌或豬鏈球菌毒力、免疫原性、生長、代謝、調控等功能相關相關。其中豬鏈球菌HP0197、S0153、1358hk、GlnA、HMRG、副豬嗜血桿菌lon等6個基因白缺失后細菌完全不致病或細菌不能生長，是潛在的藥物靶標和重要毒力因子。副豬嗜血桿菌PalA，Omp2，D15，HPS_06257、HPS_2063、HPS_0687、OAPA等7個基因是重要免疫原性基因。鑒定了豬鏈球菌SSP、IgA、副豬嗜血桿菌等3個重要毒力因子。進一步對可能的新藥靶標進行了研究，初步獲得了1358hk、HMRG 2個新藥靶標結構和先導化合物抑制劑。

關鍵詞：豬鏈球菌 副豬嗜血桿菌 新藥靶標

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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