Infectious Diseases are commonly encountered illness that may pose great impact on human health, quality of life, and social economical issues as a whole. In the past 70 years, more than half of the 335 human infectious diseases discovered are caused by bacterial infection. Thus, successful control of bacterial infection is the key to fight off infectious diseases. Also, due to overuse and misuse of antimicrobials, bacterial resistance to antibiotics keeps on emerging and accumulating, which makes traditional antimicrobial chemotherapy less and less effective against drug-resistant pathogens.
Our research is mainly focused on four aspects:
1. Bacterial programmed cell death (PCD) and stress response systems as targets for novel antimicrobials and antimicrobial potentiators:
During billions of years of evolution, bacteria have acquired self-protective pathways that can actively sense and response to external lethal stress to ensure population proliferation and persistence. A better understanding of bacterial PCD and stress response network is expected to help enhance the ability of both host defence and antimicrobial treatment to kill bacterial pathogens, which will in turn rapidly reduce bacterial load, help shorten treatment time, and suppress the development of resistance.
Selected Publicatons:
Dorsey-Oresto A, Lu T, Mosel M, Wang X, Salz T, Drlica K, Zhao X. (2013) Cell Rep. 21;3(2):528-37.
Wang X and Zhao X. (2009) Antimicrobial Agents Chemother 53(4):1395-402.
Wu X, Wang X, Drlica K, Zhao X. (2011) PLoS One 6(8):e23909.
2. Molecular mechanisms of antimicrobial lethal action
We are presently focusing on molecular mechanisms underlying the lethal action of fluoroquinolones and bicyclomycin. The outcome of our work will help refine antimicrobials currently available by drastically improving their lethal activity and reducing their propensity to select resistant mutants. This work is expected to provide us new weapons to overcome antimicrobial resistance.
Selected Publications：
Wang X, Zhao X. (2009) Antimicrob Agents Chemother 53:1395-1402
Wang X, Zhao X. Malik M, et al. (2010) J Antimicrobial Chemother 65:520-524
Drlica K, Malik M, Kerns RJ, Zhao X. (2008) Antimicrob Agents Chemother 52:385-92.
(Adapted from: http://www.yin.kit.edu/english/959_205.php)
3. Mutant prevention concentration (MPC) and Mutant Selection Window (MSW) as guidance to control antimicrobial resistance
In collaboration with Professor Karl Drlica, Professor Xilin Zhao proposed, established, and validated the Mutant Selection Window (MSW) and the Mutant Prevention Concentration (MPC) hypothesis. MPC is the minimal drug concentration that prevents the selective enrichment of first-step (next-step) resistant mutant bacterial subpopulations. MSW refers to the drug concentration window between MPC and the minimal inhibitory concentration (MIC). The MSW theory provides new thoughts and strategies for suppressing the development of drug resistance and guiding the prudent use of antimicrobials. So far more than 350 publications related to MSW and MPC have been published; MPC and MSW have been chosen as automatically selected key words by Journals such as AAC and JAC.
Selected Publications:
Cui J, Liu Y, Wang R, Tong W, Drlica K, Zhao X. (2006) J Infect Dis. 194(11):1601-8.
Zhao X, Drlica K. (2002) J Infect Dis. 185(4):561-5.
Zhao X, Drlica K.(2001) Clin Infect Dis. 33 Suppl 3:S147-56.
4. Molecular mechanisms of bacterial pathogenesis：
While traditional antibiotics can inhibit bacterial growth and/or kill bacteria, they also create favourable conditions for selection of drug resistant mutants. Production of virulence factors usually has no effect on bacterial growth. However, when either the expression or the function of virulence factors is jeopardized, bacteria would partially or completely loose their ability to invade their hosts. Thus, studies on the expression control and functions of virulence factors may help develop novel anti-bacterials less prone to development of drug resistance.
Selected Publications：
Wang D,et al. (2011) J Biol Chem286, 29922-31 (Faculty of 1000 “Recommended”);
Tree JJ, Wang D, et al. (2009) Infect Immun
77, 4209-20;
Wang D, et al. (2008) Mol Microbiol 69, 1499-512;