本实验室主要研究急性细菌感染性疾病发病的分子机制。急性细菌性肺炎、败血症等感染性疾病是当今世界范围内导致儿童和老年人死亡的最重要原因之一，其主要病原体包括肺炎链球菌（Streptococcus pneumoniae）、肺炎克雷伯菌（Klebsiella pneumoniae）、大肠埃希菌（Escherichia coli）、金黄色葡萄球菌（Staphylococcus aureus）等。 尽管人体的天然免疫系统（如吞噬性白细胞、补体、抗菌肽等）能够发现、捕捉并消灭非致病菌，但是在面对高毒力菌株或机体免疫功能低下时无法彻底清除病原体。因此，病原体在体内成功逃逸宿主天然免疫监控并大量增殖是导致急性肺炎及败血症的主要根源，然而目前在国际范围内对发病的分子机制缺乏理解。值得一提的是，日益增强的细菌耐药已经使过去用于治疗细菌感染的许多抗生素不再有效。据此，本实验室目前的主要科学问题包括：1） 病原菌依赖哪些自身的基因及其相关功能来达到逃逸宿主天然免疫监控的目的；2） 人体的哪些免疫细胞和免疫分子在清除非致病菌中发挥作用，却容忍致病菌的生存与繁殖。解决这些重大科学问题将为急性细菌感染性疾病的精准诊断、治疗和预防提供新的分子靶标与思路。

近5年代表性科研论文：

1.Xianbin Tian; Juanjuan Wang; Haoze Chen; Ming Ding; Qian Jin;Jing-Ren Zhang*; 2024,In vivo Functional Immunoprotection Correlates for Vaccines against Invasive Bacteria,Vaccine, 42(4): 853-863

2.Chengwang Zhang; Yanhong Liu; Haoran An; Xueying Wang; Lina Xu; Haiteng Deng; Songquan Wu;Jing-Ren Zhang; Xiaohui Liu; 2023, Amino acid starvation-induced glutamine accumulation enhances pneumococcal survival,mSphere, 8(3): 00625-22

3.Juanjuan Wang; Haoran An; Ming Ding; Yanhong Liu; Shaomeng Wang; Qian Jin; Qi Wu; Haodi Dong; Qile Guo; Xianbin Tian; Jiankai Liu; Jingfei Zhang; Tao Zhu; Junqiang Li; Zhujun Shao; David E. Briles; Jan-Willem Veening; Haifa Zheng; Linqi Zhang;Jing-Ren Zhang*; 2023, Liver macrophages and sinusoidal endothelial cells execute vaccine-elicited capture of invasive bacteria,Science Translational Medicine, 15(727)

4.Haoran An; Xianbin Tian; Yijia Huang;Jing-Ren Zhang*; 2023, Identification of the mouseKupffercell receptors recognizing pneumococcal capsules by affinity screening,STAR Protocols, 4(102065)

5.Lijun Wang; Xueting Huang; Qian Jin; Jie Tang; Hua Zhang;Jing-Ren Zhang*; Hui Wu; 2023,Two Component Response Regulator OmpR Regulates Mucoviscosity through Energy Metabolism inKlebsiella pneumoniae,Microbiology Spectrum, 11(3)

6.Haoran An; Chenyun Qian; Yijia Huang; Jing Li; Xianbin Tian; Jiaying Feng; Jiao Hu; Yujie Fang; Fangfang Jiao; Yuna Zeng; Xueting Huang; Xianbin Meng; Xue Liu; Xin Lin; Zhutian Zeng; Martin Guilliams; Alain Beschin; Yongwen Chen; Yuzhang Wu; Jing Wang; Marco Rinaldo Oggioni; John Leong; Jan-Willem Veening; Haiteng Deng; Rong Zhang; Hui Wang; Jiang Wu; Yan Cui;Jing-Ren Zhang*; 2022,Functional vulnerability of liver macrophages to capsules defines virulence of blood-borne bacteria,Journal of Experimental Medicine, 219(4): e20212032

7.Xueting Huang; Xiuyuan Li; Haoran An; Juanjuan Wang; Ming Ding; Lijun Wang; Lulu Li; Quanjiang Ji; Fen Qu; Hui Wang; Yingchun Xu; Xinxin Lu; Yuan He;Jing-Ren Zhang*; 2022, Capsule type defines the capability ofKlebsiella pneumoniaein evading Kupffer cell capture in the liver,PLoS Pathogens, 18(8): e1010693-e1010725

8.Menglan Zhou; Ziran Wang; Li Zhang; Timothy Kudinha; Haoran An; Chenyun Qian; Bin Jiang; Yao Wang; Yingchun Xu; Zhengyin Liu; Hong Zhang;Jing-Ren Zhang*;2022, Serotype distribution, antimicrobial susceptibility, multilocus sequencing type and virulence of invasiveStreptococcus pneumoniaein China: a six-year multi-center study,Frontiers in Microbiology, 12(798750)

9.Ziyi Guo, Haoqi Yang,Jing-Ren Zhang, Wenyen Zeng*, and Xiaoyu Hu*. 2022. Leptin receptor signaling sustains metabolic fitness of alveolar macrophages to attenuate pulmonary inflammation.Science Advances. 8(28)

10.Chengwang Zhang; Haoran An; Jiao Hu; Jing Li; Wenhao Zhang; Xun Lan; Haiteng Deng; Jing-Ren Zhang*; 2021, MetR is a molecular adaptor for pneumococcal carriage in the healthy upper airway,Molecular Microbiology, 116(2): 438-458

11.Qingqing Hu, Huichun Tong, Jing Wang, Pupu Ge, Lin Zhu, Cuihua Liu,Jing-Ren Zhang, Xiuzhu Dong. 2021.A novel aquaporin subfamily imports oxygen and contributes to pneumococcal virulence by controlling production and release of virulence factors.mBio12: e01309-21. https://doi.org/10.1128/mBio.01309-21.

12.Juanjuan Wang; Jing-Wen Li; Jing Li; Yijia Huang; Shaomeng Wang;Jing-Ren Zhang*,Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems,PLoS Pathogens, 16(3): e1008417

13.Huang Xueting, Juanjuan Wang, Jing Li, Yanni Liu, Xue Liu, Zeyao Li, Kurni Kurniyati, Yijie Deng, Guilin Wang, Joseph D. Ralph,Megan De Ste Croix,Sara Escobar-Gonzalez,Richard J. Roberts,Jan-Willem Veening, Xun Lan, Marco R. Oggioni^*, Chunhao Li^*,andJing-Ren Zhang*. 2020. Prevalence of phase variableepigenetic invertons among host-associatedbacteria.Nucleic Acids Research48:11468-11485. DOI:10.1093/nar/gkaa907.

14.Li Jing.-Wen, Juanjuan Wang, Sofia Ruiz-Cruz, Manuel Espinosa,Jing-Ren Zhang*, and Alicia Bravo*. 2020.In vitro DNA inversions mediated by the PsrA site-specific tyrosine recombinase ofStreptococcus pneumoniae.Frontiers in Molecular Biosciences7:43.DOI:10.3389/fmolb.2020.00043.

15.Li Jing-Wen, Jing Li, Juanjuan Wang, Chunhao Li, andJing-Ren Zhang*. 2019.Molecular mechanisms ofhsdSinversionsin thecodlocus ofstreptococcus pneumoniae.Journal of Bacteriology201(6): e00581-18. DOI:10.1128/JB.00581-18.Chosen by the editor astheArticle of Significant Interest in This Issue,DOI:10.1128/JB.00023-19.

16.Liu,Yanni, YunaZeng,YijiaHuang, Gu L,ShaolinWang,ChunhaoLi,Donald A.Morrison,HaitengDeng*,Jing-RenZhang*. 2019.HtrA‐mediated selective degradation of DNA uptake apparatus accelerates termination of pneumococcal transformation.Molecular Microbiology112：1308-1325. DOI:10.1111/mmi.14364.

17.Li, Jing andJing-Ren Zhang*. 2019. Phase variation ofStreptococcus pneumoniae.Microbiology Spectrum7(1). DOI:10.1128/microbiolspec.GPP3-0005-2018.

18.Zong,Yu,FangFang,Kirsten J.Meyer,Liguo Wang, Zhihao Ni, Hongying Gao. Kim Lewis,Jing-Ren Zhang, and Yu Rao.2019.Gram-scale total synthesis of teixobactin promoting binding mode study and discovery of more potent antibiotics.Nature Communications10:3268.DOI:10.1038/s41467-019-11211-y.

19.Zhang, Kai,Zhuan Qin, Yunjie Chang,Jun Liu, Michael G. Malkowski, Saimtun Shipa, Li Li, Weigang Qiu,Jing-Ren Zhang, and Chunhao Li*. 2019. Analysis of a flagellar filament cap mutant reveals that HtrA serine protease degrades unfolded flagellin protein in the periplasm ofBorrelia burgdorferi.Molecular Microbiology111:1652-1670.DOI:10.1111/mmi.14243.

20.Wang, Xu, Yuna Zeng, Li Sheng, Peter Larson, Xue Liu, Xiaowen Zou, Shufang Wang, Kaijing Guo, Chen Ma, Gang Zhang, Huaqing Cui, David Ferguson, Yan Li,Jing-Ren Zhang*, and Courtney Aldrich*. 2019. A cinchona alkaloid antibiotic that appears to target ATP synthase inStreptococcus pneumoniae.Journal of Medicinal Chemistry62:2305-2332.DOI:10.1021/acs.jmedchem.8b01353.