Our laboratory works on the molecular mechanisms of acute bacterial pneumonia and related diseases. Community and hospital-acquired pneumonia is a major cause of morbidity and mortality in young children and individuals with advanced age. Bacterial resistance to antimicrobials has made increasingly more difficult to treat pneumonia. The common pathogens include Streptococcus pneumoniae, Klebsiella pneumoniae, and Mycoplasma pneumoniae. It is well known that pneumonia relies on the successful survival and growth of the pathogens in the lungs through microbial escape of host immune surveillance that is otherwise able to eradicate all non-pathogenic microorganisms. However, precise mechanisms of pneumonia pathogenesis remain sketchy. The following are some of the key questions we are interested: 1) what are the bacterial genes and functions that enable the pathogens to survive and replicate in the host environment; 2）what are the host cells and molecules that are able to kill non-pathogenic microbes but not the pathogens; 3) what are the gaps in the host innate immune surveillance that allows the survival and replication of the pathogens (but not commensals). The answers to these questions will identify bacterial virulence factors and host immunity gaps that can be used to develop novel markers for pneumonia diagnosis and new therapeutics for pneumonia treatment and prevention.

Research Articles

1.Chengwang Zhang, Haoran An, Jiao Hu, Jing Li , Wenhao Zhang, Xun Lan, Haiteng Deng,Jing-Ren Zhang*. MetR is a molecular adaptor for pneumococcal carriage in the healthy upper airway.Molecular Microbiology, 2021. DOI: 10.1111/mmi.14724.

2.Xueting Huang, 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*. Prevalence of phase variable epigenetic invertons among host-associated bacteria[J].Nucleic Acids Research, 2020, 48(20):11468–11485.

3.Wang Juanjuan, Jing-Wen Li, Yijia Huang, Shaolin Wang, andJing-Ren Zhang*. Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems.PLoS Pathogens,2020,16 (3): e1008417.

4.Jingwen Li, Juanjuan Wang, Sofia Ruiz-Cruz, Manuel Espinosa, Jing-Ren Zhang*, and Alicia Bravo*. In vitro DNA inversions mediated by the PsrA site-specific tyrosine recombinase of Streptococcus pneumoniae.Frontiers in Molecular Biosciences, 2020, 7: 43.

5.YanniLiu, Yuna Zeng, Yijia Huang, Gu L, Shaolin Wang, Chunhao Li, Donald A. Morrison, Haiteng Deng*,Jing-Ren Zhang*. HtrA‐mediated selective degradation of DNA uptake apparatus accelerates termination of pneumococcal transformation.Molecular Microbiology, 2019, 112(4): 1308-1325.

6.Jing-WenLi, Jing Li, Juanjuan Wang, Chunhao Li, andJing-Ren Zhang*. Molecular mechanisms ofhsdSinversions in thecodlocus ofStreptococcus pneumoniae.Journal of Bacteriology, 2019,201(6):e00581-18.

7.Xu Wang, 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*.A cinchona alkaloid antibiotic that appears to target ATP synthase in Streptococcus pneumoniae.Journal of Medicinal Chemistry, 2019, 62(5): 2305-2332.

8.LihongHe, Dongyang Luo, Fan Yang, Chunhao Li, Xuegong Zhang, Haiteng Deng, andJing-Ren Zhang*. Multiple domains of bacterial and human Lon proteases define substrate selectivity.Emerging Microbes and Infections,2018, 7(1): 149.

9.Yang Wang, Zhensong Wen, Xiaolei Pan, David E.Briles, Yongqun He,Jing-Ren Zhang*. Novel immunoprotective proteins ofStreptococcus pneumoniaeidentified by opsonophagocytosis killing screen.Infection and Immunity, 2018,86(9):e00423-18.

10.Bo Liu, Xue Liu,Jing-Ren Zhang*, and Gang Liu*. A natural lipotrisaccharide and its derivatives selectively lyseStreptococcus pneumoniaevia interaction with cell membrane. ACS Infectious Diseases, 2017,3(6):438-453.

11.Xue Liu, Jing-Wen Li, Zhixin Feng, Yongfu Luo, Jan-Willem Veening, andJing-Ren Zhang*.Transcriptional repressor PvtR regulates phenotypic tolerance to vancomycin inStreptococcus pneumoniae.Journal of Bacteriology, 2017, 199(14): e00054-17.

12.Fei Chen, Guolin Cui, Shuxia Wang, Manoj K. Mohan Nair, Lihong He, Xinyi Qi, Xiangmin Han, Hanqi Zhang,Jing-Ren Zhang*, and Jingliang Su*. Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and virulence inFrancisella tularensisLVS.Emerging Microbes and Infections, 2017, 6(7): e66.

13.Jing Li,Jing-Wen Li, Zhixin Feng, Juanjuan Wang, Haoran An, Yanni Liu, Yang Wang, Kailing Wang, Xuegong Zhang, Zhun Miao, Wenbo Liang, Robert Sebra, Guiling Wang, Wen-Ching Wang, andJing-Ren Zhang*. Epigenetic switch driven by DNA inversions dictates phase variation inStreptococcus pneumoniae.PLoS Pathogens, 2016,12(7): e1005762.

14.Zhensong Wen, Yanni Liu, Fen Qu, andJing-Ren Zhang*. Allelic variation of the capsule promoter diversifies encapsulation and virulence inStreptococcus pneumoniae.Scientific Reports, 2016, 6:30176.

15.Guilin Li, Zhuowen. Liang, Xiatai Wang, Yonghong Yang, Zhujun Shao, Ma Li, Yueyun Ma, Fen Qu, Donald A. Morrison, andJing-Ren Zhang*.Addiction of hyper-transformable pneumococcal isolates to natural transformation forin vivofitness and virulence.Infection and Immunity, 2016, 84(6): 1887-1901.

16.Lihong He, Manoj K. Mohan Nair, Yuling Chen, Xue Liu, Mengyun Zhang, Karsten R. O. Hazlett, Haiteng Deng*, andJing-Ren Zhang*.The protease locus ofFrancisella tularensisLVS is required for stress tolerance and infection of mammalian host.Infection and Immunity, 2016, 84(5): 1387-402.

17.Xiao-Hui Bai, Qiong Li, Yong-Liang Jiang,Jing-Ren Zhang*, Yuxin Chen*, and Cong-Zhao Zhou*. Structural comparison and simulation of pneumococcal peptidoglycan hydrolase LytB.Methods in Molecular Biology, 2016, 1440:271-83.

18.Hongzhi Yang, Xue Liu, Qingong Li, Longbo Li,Jing-Ren Zhang*, and Yefeng Tang*.Total synthesis and preliminary SAR study of (+/-)-merochlorins A and B.Organic & Biomolecular Chemistry, 2016, 14(1): 198-205.

Book chapter

1.Jing Li and Jing-Ren Zhang*. 2019. Phase variation ofStreptococcus pneumoniae. In Gram-Positive PathogensReference(Vincent A. Fischetti ed.) (book chapter). American Society for Microbiology Press, Washington, D.C.

2.Jing-Ren Zhang*, M. G. Marinus, and Haiteng Deng. 2015. Methylation and other modifications of nucleic acids and proteins. InReference Module in Biomedical Sciences(Michael Caplan ed.), chapter 2448 (book chapter). Page 1-11, DOI: 10.1016/B978-0-12-801238-3.02448-X, Elsevier, Amsterdam.

3.Zhensong Wen, andJing-Ren Zhang*. 2015. Bacterial capsules, p. 33-52 (book chapter). InMolecular Medical Microbiology(Y.-W. Tang, M. Sussman, D. Liu, I. Poxton, and J. Schwartzman ed.). Academic Press, Amsterdam.