猪链球菌等重要病原菌的致病机理和防控技术研究

研究猪链球菌等重要动物细菌重要的毒力因子与宿主的相互作用及其信号传导途径，探讨致病因子在逃避和抑制免疫应答中的作用，揭示猪链球菌等重要病原菌的致病机理，鉴定新的药物靶标，筛选和评价新的抗菌制剂。

1. 国家自然科学基金面上项目：猪链球菌2型半胱氨酸蛋白酶ApdS切割宿主防御肽cathelicidin LL-37介导其免疫逃逸的分子机制（31873016，2019.01-2022.12）, 67万元；

2. 国家自然科学基金青年科学基金项目：猪胸膜肺炎放线杆菌ClpP蛋白酶的致病机理研究（31100103，2012.01-2014.12），24万元；   

3. 黑龙江省科学基金青年项目：猪链球菌2型SSU05_1311蛋白与纤连蛋白互作介导其黏附和侵入宿主细胞的分子机制（QC2016044，2016.07-2019.07），5万元。

一、代表论文与著作

1.Fang Xie, Yanan Zan, Xinyuan Zhang, Huihui Zhang, Mingjie Jin, WanjiangZhang, Yueling Zhang, Siguo Liu*. Differential abilities of mammalian cathelicidinsto inhibit bacterial biofilm formation and promote multifaceted immunefunctions of neutrophils. International Journal of Molecular Sciences, 2020,21(5):1871.

2.Fang Xie, Yanan Zan, Yueling Zhang, Ning Zheng, Qiulong Yan, WanjiangZhang, Huihui Zhang, Mingjie Jin, Fuguang Chen, Xinyuan Zhang, Siguo Liu*. Thecysteine protease ApdS from Streptococcus suis promotes evasion ofinnate immune defenses by cleaving the antimicrobial peptide cathelicidinLL-37. Journal of Biological Chemistry, 2019, 294(47): 17962-17977.

3. Fang Xie, Yalei Wang, Gang Li, Shuanghong Liu, Ning Cui, Siguo Liu, Paul R.Langford and Chunlai Wang. The SapA protein is involved in resistance toantimicrobial peptide PR-39 and virulence of Actinobacillus pleuropneumoniae. Frontiers in Microbiology. 2017, 8:811.

4.Fang Xie, Gang Li, Yalei Wang, Yanhe Zhang, LongZhou, Chengcheng Wang, Shuanghong Liu, Siguo Liu, Chunlai Wang. Pyridoxalphosphate synthases PdxS/PdxT are required for Actinobacillus pleuropneumoniae viability, stress tolerance andvirulence. PLoS One. 2017, 12(4): e0176374.

5. FangXie, Gang Li, Long Zhou, Yanhe Zhang, Ning Cui, Siguo Liu, Chunlai Wang.Attenuated Actinobacilluspleuropneumoniae double-deletion mutant S-8∆clpP/apxIIC confersprotection against homologous or heterologous strain challenge. BMC VeterinaryResearch. 2017, 13(1): 14.

6. Gang Li#, Fang Xie#,Jianjun Li, Jiao Liu, Dapeng Li, Yanhe Zhang, Paul R. Langfordb, Yanwen Li, SiguoLiu, Chunlai Wang. Identification of novel Haemophilusparasuis serovar 5 vaccine candidates using an immunoproteomic approach.Journal of Proteomics.2017, 163: 111-117.

7. Fang Xie, Gang Li, Wanjiang Zhang, YanheZhang, Long Zhou, Shuanghong Liu, Siguo Liu, Chunlai Wang. Outer membranelipoprotein VacJ is required for the membrane integrity, serum resistance andbiofilm formation of Actinobacilluspleuropneumoniae. Veterinary Microbiology. 2016, 183: 1-8,

8. Fang Xie, Gang Li,Yanhe Zhang, Long Zhou, Shuanghong Liu, Siguo Liu, Chunlai Wang. The Lonprotease homologue LonA, not LonC, contributes to the stress tolerance andbiofilm formation of Actinobacilluspleuropneumoniae. Microbial Pathogenesis. 2016, 93: 38-43.

9. FangXie, Yanhe Zhang, Gang Li, Siguo Liu, Chunlai Wang. The ClpP protease isrequired for the stress tolerance and biofilm formation in Actinobacillus pleuropneumoniae. PLoS One. 2013, 8(1): e53600.

10. FengYang#,Fang Xie#, Yuwen Jiang,Suqing Li, Yanping Xing, Yu Wang, Xin Feng, Wenyu Han, Liancheng Lei. GenomicDifferences Between Actinobacilluspleuropneumoniae Serotypes 5b and 3 and their Distribution andTranscription Among 15 Serotypes. Current Microbiology. 2011, 63(4): 327-331.

11. Fang Xie, LianchengLei, Chongtao Du, Shuqing Li, Wenyu Han, Zhiyan Ren. Genomic differencesbetween Actinobacillus pleuropneumoniaeserotypes 1 and 3 and the diversity distribution among 15 serotypes. FEMSMicrobiology Letters. 2010, 303(2): 147-155.

12. Fang Xie, MingjunZhang, Shuqing Li, Chongtao Du, Changjiang Sun, Wenyu Han, Liang Zhou,Liancheng Lei. Differentially expressed genes in the pathogenic strains of Actinobacillus pleuropneumoniaeserotypes 1 and 3. Journal of Microbiology and Biotechnology. 2010, 20(4):789-797.

二、专利

1.谢芳，王春来，张艳禾，李建军，朱晓凯，李艳玲，一种不含抗性标记的猪胸膜肺炎放线杆菌ClpP蛋白酶基因缺失株、其构建方法及应用，ZL 201110336861.3

2. 谢芳，刘思国，张万江，张跃灵，一种新型广谱抗菌肽及其应用，ZL 202010037156.2

3. 王春来，谢芳，李刚，张艳禾，一种不含抗性标记的猪传染性胸膜肺炎弱毒活疫苗及其用途，ZL 201310469680.7

4. 王春来，谢芳，张艳禾，李刚，一种不含抗性标记的猪胸膜肺炎放线杆菌双基因缺失株、其构建方法及应用，ZL 201110420236.7

5. 王春来，李刚，张艳禾，谢芳，一种副猪嗜血杆菌病亚单位疫苗组合物及应用，ZL 201310406551.3

6. 王春来，李刚，张艳禾，谢芳，一种制备副猪嗜血杆菌病菌影疫苗的方法及其产品和应用，ZL 201310409237.0

7. 王春来，李刚，张艳禾，谢芳，一种副猪嗜血杆菌免疫保护性抗原AfuA，ZL 20131 0268347.X

8. 李刚，王春来，张艳禾，谢芳，一种副猪嗜血杆菌免疫保护性抗原HbpA，ZL 20131 0268864.7；

9. 王春来，李刚，张艳禾，谢芳，一种副猪嗜血杆菌免疫保护性抗原OppA，ZL 20131 0268863.2

10. 王春来，李刚，张艳禾，谢芳，一种副猪嗜血杆菌免疫保护性抗原OppA2，ZL 2013 10268810.0

三、获得奖励（成果奖励和个人荣誉，不超过10项）

1. 猪传染性胸膜肺炎菌影疫苗的研制及其应用，黑龙江省科技进步三等奖，王春来，李刚，谢芳，张艳禾，李艳玲，周泷，2017年

2. 猪传染性胸膜肺炎菌影疫苗的研制及其应用，哈尔滨市科技进步二等奖，王春来，李刚，谢芳，张艳禾，李艳玲，周泷，2016年

3. 基于比较基因组学的胸膜肺炎放线杆菌黏附致病机制及异源免疫研究，吉林省自然科学学术成果奖二等奖，雷连成，冯新，杨舒心，谢芳，王瑜，杜崇涛等，2014年