报告题目：肠道细菌的脂代谢与耐药性

报告时间：2017年12月27日下午15:00

报告地点：学院（兽医楼）三楼会议室

报 告 人：冯友军 教授/博士研究生导师

报告人简介：

冯友军博士系浙江大学医学院感染与免疫中心教授/博士研究生导师, 入选中组部“青年” (第五批)。主要从事肠道细菌脂肪酸代谢与致病/耐药。通过对病原细菌脂肪酸代谢调控多样化的调控网络的认识, 为以维生素代谢调控等研究发现作为药物靶点开展小分子抑制剂/药物设计提供知识储备和理论基础。目前已获得国家青年项目,国家自然基金面上项目和浙江省杰出青年基金的支持。迄今为止, 已在本领域的数十种知名国际学术期刊上发表了80余篇研究论文(Science, PLoS Medicine, PLoS Pathogens, mBio, Nature Microbiology, Molecular Microbiology, The Journal of Infectious Diseases, Emerging Infectious Diseases, The Journal of Biological Chemistry, Journal of Bacteriology, Journal of Virology, Infection and Immunity, Journal of Clinical Microbiology, Antimicrobial Agents and Chemotherapy, ACS Chemical Biology, Journal of Molecular Biology, Virulence, Microbiology-SGM等), 累计引用3000余次。作为重要成员荣获2011年度中华医学一等奖, 2011年度中华预防医学一等奖以及2014年度国家科技进步二等奖, 目前担任Virulence (IF: 5.418) 与Scientific Reports (IF: 5.228)在内的多家刊物的编委。

报告摘要：

病原菌引起的传染性疾病已经发展成为人类健康的一个重大威胁, 每年在世界范围内有数百万人因感染致病菌而死亡。近年来由于抗生素的滥用, 导致了一系列耐多种抗生素的超级细菌的凸现(如多粘菌素耐药的MCR-1和超级细菌NDM-1)。这给公共卫生领域带来了严峻的挑战, 同时也对挖掘新型抗细菌的药物靶标并开发新型抗生素提出了迫切要求。脂肪酸作为一个细胞膜的基本组分，其在高等生物体(包括哺乳动物) 内的合成机制与细菌的生物合成机制是截然不同的(哺乳动物采用I型脂肪酸合成机制, 而细菌则采用II型脂肪酸合成机制)。因此, 这种脂肪酸代谢机制的异同已被逐渐发展为一个潜在的新型抗细菌的药物靶点。生物素(C7骨架的biotin)和硫辛酸(C8骨架的lipoic acid)是2种含硫脂肪酸衍生物类维生素, 在生物体的代谢过程中扮演了不可或缺的辅酶角色。这2类维生素主要始于脂肪酸合成过程, 但只有植物、真菌和一些细菌(包括病原细菌)能合成产生。新近的研究揭示这2种维生素可作为营养性毒力因子参与病原细菌的致病机制。因此阻断细菌对这2类维生素吸收和生物合成途径可作为全新的抗菌靶标, 也将为改善当下病原菌对多类抗生素产生抗药性/耐药性的境况成为可能。当前几类重要的抗肺结核的复合物,其作用靶标是肺结核菌生物素合成途径中的关键酶。因此，对病原细菌维生素利用及其合成调控机制的深入解析将为新抗菌靶标的挖掘/小分子药物设计提供强有力的理论支持。我们的报告将介绍肠道细菌的脂肪酸及衍生物的代谢调控机制与其在细菌感染过程中所扮演的角色。尤为重要的是, 针对时下公共卫生领域的新挑战 (即MCR-1多黏菌素耐药), 给出了其脂肪酸代谢的重要视点。

近3年发表论文 (2014-2016)：

2016

1. Li XP, Fang LX, Song JQ, Xia J, Huo W, Fang JT, Liao XP, Liu YH, Youjun Feng*, Sun J*. Clonal spread of mcr-1 in PM-carrying ST34 Salmonella isolates from animals in China. Sci Rep. 2016 Dec 5; 6: 38511. doi: 10.1038/srep38511. *corresponding author

2. Gao RS, Hu YF, Li ZC, Sun J, Wang QJ, Lin JX, Ye HY, Liu F, Srinivas S, Li DF, Zhu BL, Liu YH, Tian GB, Youjun Feng*. Dissemination and mechanism for the MCR-1 colistin resistance, 2016, PLoS Pathogens, 12 (11): e1005957. doi: 10.1371/journal.ppat.1005957. *corresponding author

3. Wang QJ, Li ZC, Lin JX, Wang XN, Deng XB, Youjun Feng *. Complex dissemination of the diversified mcr-1-harbouring plasmids in Escherichia coli of different sequence types, 2016, Oncotarget, doi: 10.18632/oncotarget.12621. *corresponding author

4. Sun J, Liao XP, Liu YH, Youjun Feng*. One health: An approach to resolving antibiotic resistance. 2016, Infect Dis Transl Med. (Invited review), on line. *corresponding author

5. Sun J, Yang RS, Zhang QJ, Youjun Feng, et al. Co-transfer of blaNDM-5 and mcr-1 by an IncX3-X4 hybrid plasmid in Escherichia coli , Nature Microbiology, 2016, 1:16176. doi: 10.1038/nmicrobiol.2016.176.

6. Yang RS, Youjun Feng, et al. Emergence of NDM-5 and MCR-1-producing Escherichia coli clone ST648 and ST156 from a single muscovy duck (Cairina moschata). Antimicrob Agents Chemother. 2016 Aug 22. pii: AAC.01365-16. [Epub ahead of print]

7. Li Z, Tan C, Lin J, Youjun Feng*. Diversified variants of the mcr-1-carrying plasmid reservoir in the swine lung microbiota. Sci China Life Sci. 2016， 59 (9): 971-973. *corresponding author

8. Rongsui Gao…… Youjun Feng*, Genome sequence and characteristics of plasmid pWH12, a variant of the mcr-1-harbouring plasmid pHNSHP45, from the multi-drug resistant E. coli. Virulence. 2016; 7(6):732-5. * corresponding author

9. Gao R, Li Y, Lin J, Tan C, Feng Y*. Unexpected complexity of multidrug resistance in the mcr-1-harbouring Escherichia coli. Sci China Life Sci. 2016 Jul; 59(7):732-4. * corresponding author

10. Xiaolu Shi …… Youjun Feng*, Loss of 89K pathogenicity island in epidemic Streptococcus suis, China, Emerg Infect Dis. 2016, Epub ahead of print * corresponding author

11. Huimin Zhang …… Youjun Feng*, Deciphering a unique biotin scavenging pathway with redundant genes in the probiotic bacterium Lactococcus lactis, Sci Rep. 2016, Epub ahead of print * corresponding author

12. Huiyan Ye …… Youjun Feng*, Functional definition of BirA suggests a biotin utilization pathway in the zoonotic pathogen Streptococcus suis

Sci Rep. 2016, Epub ahead of print * corresponding author

13. Huiyan Ye …… Youjun Feng*, Diversified mcr-1-harbouring plasmid reservoirs confer resistance to colistin in human gut microbiota, mBio, 2016 Apr 5; 7(2). pii: e00177-16. doi: 10.1128/mBio.00177-16. * corresponding author

14. Huimin Zhang, Swaminath Srinivas, Defeng Li, Youjun Feng*, Origin, dissemination and entry of the pandemic Zika viruses, Science Bulletin 2016, Epub ahead of print * corresponding author

15. Huimin Zhang, Christopher H Seward, Zuowei Wu, Huiyan Ye, Youjun Feng*, Genomic insights into the ESBL and MCR-1-producing ST648 Escherichia coli with multi-drug resistance, Science Bulletin 2016, Epub ahead of print * corresponding author

16. Min Cao…… Youjun Feng*, Determination of Scrub typhus suggests a new epidemic focus in the Anhui province of China, Sci Rep. 2016 Feb 10; 6: 20737. doi: 10.1038/srep20737. * corresponding author

17. Rongsui Gao, Jingxia Lin, Huimin Zhang, Youjun Feng*, Transcriptional repression of the VC2105 by the Vibrio FadR suggests a new auxiliary member of the fad regulon, Appl Environ Microbiol. 2016 Mar 4. pii: AEM.00293-16. [Epub ahead of print]. * corresponding author

18. Deng C …… Youjun Feng*, Xianbo Deng*, Deoxynivalenol inhibits proliferation and induces apoptosis in human umbilical vein endothelial cells, Environ Toxicol Pharmacol. 2016 Mar 26; 43: 232-241. doi: 10.1016/j.etap.2016.02.002. [Epub ahead of print]. * corresponding author

2015

19. Youjun Feng, Chui-Yoke Chin, Vandana Chakravartty, Rongsui Gao, David S. Weiss, John E. Cronan*, The atypical occurrence of two biotin protein ligases in Francisella is due to distinct roles in virulence and biotin metabolism, mBio, 2015, Jun 9;6(3). pii: e00591-15. doi: 10.1128/mBio.00591-15.

20. Huimin Zhang, Dmitry A. Ravcheev, Dan Hu, Fengyu Zhang, Xiufang Gong, Lina Hao, Min Cao, Dmitry A. Rodionov, Changjun Wang , Youjun Feng*, Two novel regulators of N- acetyl- galactosamine utilization pathway and distinct roles in bacterial infections, Microbiology Open, 2015, Accepted, * corresponding author

21. Youjun Feng*, Ritesh Kumar, Dmitry A. Ravcheev, Huimin Zhang, Paracoccus denitrificans possesses two BioR homologues having a role in regulation of biotin metabolism, Microbiology Open, 2015 June 2. doi: 10.1002/mbo3.270. [Epub ahead of print], * corresponding author

22. Huimin Zhang, Beiwen Zheng, Rongsui Gao, Youjun Feng*, Binding of Shewanella FadR to the fabA fatty acid biosynthetic gene: Implications for contraction of the fad regulon, Protein & Cell, 2015 Jun 7. [Epub ahead of print] , *corresponding author

23. Yi Sun, Henghui Wang, Xiuyu Lou, Haiyan Mao, Yong Yan, Enfu Chen, Xinying Wang, Zhen Li, Jian Gao, Xiaofei Fu, Zhongwen Chen, Youjun Feng, Zhiping Chen, Yanjun Zhang, Living poultry markets in rural area: Human infection with H7N9 virus re-emerges in Zhejiang Province, China, in winter 2014, Journal of Clinical Virology, 2015, Accepted

24. Dan Hu, Lina Hao, Jinhai Zhang, Pingping Yao, Qi Zhang, Heng Lv, Xiufang Gong, Xiuzhen Pan, Min Cao, Jin Zhu, Yun Zhang, Youjun Feng, Changjun Wang, Development of reverse transcription loop-mediated isothermal amplification assays to detect Hantaan virus and Seoul virus, Journal of Virological Methods, 2015, 221: 68-73.

25. Huimin Zhang, Qixia Luo, Haichun Gao*, Youjun Feng*, A new regulatory mechanism for bacterial lipoic acid synthesis, Microbiology Open, 2015, Jan 22. doi: 10.1002/mbo3.237 * corresponding author

26. Li M, Shao ZQ, Guo Y, Wang L, Hou T, Hu D, Zheng F, Tang J, Wang C, Youjun Feng, Gao J, Pan X. The type II histidine triad protein HtpsC is a novel adhesion with the involvement of Streptococcus suis virulence, Virulence. 2015 Jul 7:0. Epub ahead of print.

2014

27. Qing Tang, Xinfeng Li, Tingting Zou, Huimin Zhang, Yingying Wang, Rongsui Gao, Zhencui Li, Jin He*, Youjun Feng* Mycobacterium smegmatis BioQ defines a new regulatory network for biotin metabolism, Molecular Microbiology, 2014, Oct 7. doi: 10.1111/mmi.12817. [Epub ahead of print] * corresponding author

28. Yongchang Zhang, Rongsui Gao, Huiyan Ye, Qingjing Wang, Youjun Feng *, A new glimpse of FadR-DNA crosstalk revealed by deep dissection of the E. coli FadR regulatory protein. Protein & Cell, 2014, Oct 15. [Epub ahead of print] * corresponding author

29. Zhongyu Shi, ……Youjun Feng, et al. Gluconate 5-dehydrogenase (Ga5DH) participates in Streptococcus suis cell division, Protein & Cell, 2014, Oct;5(10):761-769

30. Youjun Feng, John E. Cronan, PdhR, the pyruvate dehydrogenase repressor, does not regulate lipoic acid synthesis, Research in Microbiology, 2014, Jul-Aug;165(6):429-438

31. Youjun Feng*, et al. Streptococcus suis infection: an emerging/reemerging challenge of bacterial infectious diseases? Virulence, 2014 Mar 25; 5(4). Epub ahead of print, * corresponding author

32. Dan Hu, …… Youjun Feng*, Changjun Wang*, The β-galactosidase (BgaC) of the zoonotic pathogen Streptococcus suis is an atypical surface-exposed protein without the involvement of bacterial virulence, Scientific Reports, 2014 Feb 21;4:4140

* corresponding author

33. Yang W, Lian J, Youjun Feng, et al. Genome-wide miRNA profiling of Aflatoxin B1-induced hepatic injury using deep sequencing. Toxicology Letter, 2014, Apr 21;226(2):140-9

34. Youjun Feng, et al. A Francisella virulence factor catalyzes an essential reaction of biotin synthesis. Molecular Microbiology, 2014, 91(2): 300-314.

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2017年12月26日