1. 新型测序技术在耐药菌基因组学研究中的应用

细菌耐药问题如此严重，很大程度上是由于耐药基因在不同细菌中的水平传播导致，而质粒、转座子和插入序列等遗传结构是参与耐药基因水平转移的关键因子，了解这些关键多重耐药区的基因结构是理解耐药基因进化与传播的基础。但是，由于耐药菌基因组的多重耐药区结构复杂，依据传统一代和二代测序技术，很难获得耐药菌中多重耐药质粒或者染色体的精细图谱。由于一代和二代测序读长短，无法跨越关键的多重耐药区，这就导致无法对参与耐药基因转移的关键因子如多重耐药质粒或其它耐药决定区进行系统、深入与高效分析。结合单分子测序技术，首次将其应用于多重耐药质粒结构解析和完整图谱构建，成功构建了高效的研究范例，并提出了单个质粒分子无需组装的分析策略，解决耐药菌基因组完成图难以获得的难题。以此为基础，逐渐探索新型测序技术在细菌耐药性和病原菌检测等方面的应用。

        2. 新发耐药基因传播与进化机制

发现十余个新型耐药基因转移元件和新变体，并阐明了其转移与进化特征，为细菌耐药性风险评估和防控策略的制定提供了数据支撑。肠杆菌科细菌等病原菌不仅危害畜禽健康，同时对人类健康也构成挑战，是新型耐药基因和遗传元件的“储存库”和“放大器”。针对多粘菌素和替加环素耐药新机制，从新耐药遗传元件解析、耐药质粒多样性、耐药性传播机制和进化机制等方面，系统阐明了耐药基因mcr-1和tet(X)及其传播载体的发生发展规律，为耐药性风险评估和防控策略制定提供了数据支持。

3. 耐药菌基因组流行病学与数据挖掘

阐释了重要人兽共患病原菌耐药新特征。发现单项鼠伤寒沙门氏菌变体已经成为威胁公共卫生安全的优势血清型，阐明多重耐药质粒IncHI2是其多重耐药表型的遗传基础！ 首次在高毒肺炎克雷伯菌中发现了同时携带碳青霉烯和替加环素耐药基因的杂合质粒，揭示了质粒是介导碳青霉烯和替加环素耐药基因传播的关键遗传元件。发现碳青霉烯耐药大肠杆菌中，ST131是临床优势克隆型，该克隆仅存在于人源大肠杆菌中，明确了动物源和人源耐药大肠杆菌具有不同的进化特征。为确保动物性食品安全和人类健康，避免耐药病原菌跨领域传播提供了风险数据！

代表性论文（第一作者或通讯）

1. Li R, Peng K, Xiao X, Liu Y, Peng D, Wang Z. 2021. Emergence of a multidrug resistance efflux pump with carbapenem resistance gene blaVIM-2 in a Pseudomonas putida megaplasmid of migratory bird origin. J. Antimicrob. Chemother. Doi: 10.1093/jac/dkab044.

2. Li R, Du P, Zhang P, Li Y, Yang X, Wang Z, Wang J, Bai L. 2021. Comprehensive Genomic Investigation of Coevolution of mcr genes in Escherichia coli Strains via Nanopore Sequencing. Glob Chall 5:2000014.

3. Yang X, Peng K, Zhang Y, Liu L, Li R. 2020. Characterization of a Novel mcr-8.2-Bearing Plasmid in ST395 Klebsiella pneumoniae of Chicken Origin. Infect Drug Resist 13:1781-1784.

4. Lu X, Xiao X, Liu Y, Huang S, Li R, Wang Z. 2020. Widespread Prevalence of Plasmid-Mediated Colistin Resistance Gene mcr-1 in Escherichia coli from Pere David's Deer in China. mSphere 5.

5. Liu Z, Xiao X, Liu Y, Li R, Wang Z. 2020. Recombination of NDM-5-producing plasmids mediated by IS26 among Escherichia coli. Int. J. Antimicrob. Agents 55:105815.

6. Li Y, Wang Q, Peng K, Liu Y, Li R, Wang Z. 2020. Emergence of Carbapenem- and Tigecycline-Resistant Proteus cibarius of Animal Origin. Front Microbiol 11:1940.

7. Li R, Xie M, Liu L, Huang Y, Wu X, Wang Z, Chan EWC, Chen S. 2020. Characterisation of a cointegrate plasmid harbouring blaNDM-1 in a clinical Salmonella Lomita strain. Int. J. Antimicrob. Agents 55:105817.

8. Li R, Peng K, Li Y, Liu Y, Wang Z. 2020. Exploring tet(X)-bearing tigecycline-resistant bacteria of swine farming environments. Sci. Total Environ. 733:139306.

9. Li R, Lu X, Peng K, Liu Z, Li Y, Liu Y, Xiao X, Wang Z. 2020. Deciphering the Structural Diversity and Classification of the Mobile Tigecycline Resistance Gene tet(X)-Bearing Plasmidome among Bacteria. mSystems 5.

10. Li R, Lu X, Peng K, Liu Y, Xiao X, Wang Z. 2020. Reorganization of mcr-1-bearing large MDR plasmids resolved by nanopore sequencing. J. Antimicrob. Chemother. 75:1645-1647.

11. Li R, Lu X, Liu Z, Liu Y, Xiao X, Wang Z. 2020. Rapid detection and characterization of tet(X4)-positive Escherichia coli strains with nanopore sequencing. J. Antimicrob. Chemother. 75:1068-1070.

12. Li R, Cheng J, Dong H, Li L, Liu W, Zhang C, Feng X, Qin S. 2020. Emergence of a novel conjugative hybrid virulence multidrug-resistant plasmid in extensively drug-resistant Klebsiella pneumoniae ST15. Int. J. Antimicrob. Agents 55:105952.

13. Zhang P, Bai L, Li Y, Wang Z, Li R. 2019. Loss of mcr Genes Mediated by Plasmid Elimination and ISApl1. Antimicrob. Agents Chemother. 63.

14. Yang X, Liu L, Wang Z, Bai L, Li R. 2019. Emergence of mcr-8.2-bearing Klebsiella quasipneumoniae of animal origin. J. Antimicrob. Chemother. 74:2814-2817.

15. Lu X, Xiao X, Liu Y, Li Y, Li R, Wang Z. 2019. Chromosome-mediated mcr-1 in Escherichia coli strain L73 from a goose. Int. J. Antimicrob. Agents 54:99-101.

16. Li R, Zhang P, Yang X, Wang Z, Fanning S, Wang J, Du P, Bai L. 2019. Identification of a novel hybrid plasmid coproducing MCR-1 and MCR-3 variant from an Escherichia coli strain. J. Antimicrob. Chemother. 74:1517-1520.

17. Li R, Liu Z, Peng K, Liu Y, Xiao X, Wang Z. 2019. Cooccurrence of Two tet(X) Variants in an Empedobacter brevis Strain of Shrimp Origin. Antimicrob. Agents Chemother. 63.

18. Li R, Chen K, Chan EW-C, Chen S. 2019. Characterization of the stability and dynamics of Tn6330 in an Escherichia coli strain by nanopore long reads. J. Antimicrob. Chemother. 74:1807-1811.

19. Li R, Yu H, Xie M, Chen K, Dong N, Lin D, Chan EW-C, Chen S. 2018. Genetic basis of chromosomally-encoded mcr-1 gene. Int. J. Antimicrob. Agents 51:578-585.

20. Li R, Xie M, Dong N, Lin D, Yang X, Wong MHY, Chan EW-C, Chen S. 2018. Efficient generation of complete sequences of MDR-encoding plasmids by rapid assembly of MinION barcoding sequencing data. Gigascience 7:1-9.

21. Li R, Chen K, Chan EWC, Chen S. 2018. Resolution of dynamic MDR structures among the plasmidome of Salmonella using MinION single-molecule, long-read sequencing. J. Antimicrob. Chemother. 73:2691-2695.

22. Li R, Ye L, Zheng Z, Chan EWC, Chen S. 2017. Genetic Characterization of Broad-Host-Range IncQ Plasmids Harboring blaVEB-18 in Vibrio Species. Antimicrob. Agents Chemother. 61.

23. Li R, Ye L, Wong MHY, Zheng Z, Chan EWC, Chen S. 2017. Evolution and comparative genomics of pAQU-like conjugative plasmids in Vibrio species. J. Antimicrob. Chemother. 72:2503-2506.

24. Li R, Xie M, Zhang J, Yang Z, Liu L, Liu X, Zheng Z, Chan EW-C, Chen S. 2016. Genetic characterization of mcr-1-bearing plasmids to depict molecular mechanisms underlying dissemination of the colistin resistance determinant. J. Antimicrob. Chemother. 72:393-401.

      25. Li R, Xie M, Lv J, Wai-Chi Chan E, Chen S. 2016. Complete genetic analysis of plasmids carrying mcr-1 and other resistance genes in an Escherichia coli isolate of animal origin. J. Antimicrob. Chemother. 72:696-699.

针对最新研究成果，参考ResearchGate数据库：https://www.researchgate.net/profile/Ruichao-Li-3/research