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Scientific Overview Research Interest Summary Principal Investigators    Yuri Bushkin, Ph.D.
   Theresa Chang, Ph.D.
   Neeraj Chauhan, Ph.D.
   Véronique Dartois, Ph.D.
   Thomas Dick, Ph.D.
   Karl Drlica, Ph.D.
   David Dubnau, Ph.D.
   Eliseo A. Eugenin, Ph.D.
   Marila Gennaro, M.D.
   Fred Kramer, Ph.D.
   Barry Kreiswirth, Ph.D.
   Min Lu, Ph.D.
   Leonard Mindich, Ph.D.
   Arkady Mustaev, Ph.D.
   Jyothi Nagajyothi, Ph.D.
   David Perlin, Ph.D.
   Abraham Pinter, Ph.D.
   Marcela Rodriguez, Ph.D.
   Jeanne Salje, Ph.D.
   Lanbo Shi, Ph.D.
   Selvakumar Subbian, Ph.D.
   Sanjay Tyagi, Ph.D.
   Christopher Vinnard, M.D.
   Chaoyang Xue, Ph.D.
   Xilin Zhao, Ph.D.

   Research Faculty
   Liang Chen, Ph.D.
   Eugenie Dubnau, Ph.D.
   Jeanette Hahn, Ph.D.
   Salvatore Marras, Ph.D.
   Yanan Zhao, Ph.D.

Emeritus Faculty Recent Publications
Xilin Zhao, Ph.D.

Research Summary  |  Selected Publications   |  Grant Support  |  C.V.

Public Health Research Institute Center and
Dept. Microbiology, Biochemistry & Molecular Genetics
New Jersey Medical School - Rutgers, The State University of New Jersey
225 Warren Street
Newark, New Jersey 07103

Phone: (973) 854-3366
Fax: (973) 854-3101
e-mail: zhaox5@njms.rutgers.edu

Research Summary

Bacterial resistance, tolerance, and persistence to antimicrobial treatment pose an alarming threat to human health. Dr. Zhao’s research focuses on how to maximize our ability to combat these problems. Three lines of work are currently ongoing. The first involves understanding bacterial stress-response networks with the practical aim of developing antimicrobial potentiators. Since antimicrobial exposure constitutes one of the harshest stresses that bacteria encounter, it is not surprising that genetic networks exist that can sense and respond to such stresses. By understanding and subsequently perturbing stress responses, Dr. Zhao expects to stimulate the lethal action of both antimicrobial and host immune stresses. He has identified a previously uncharacterized gene (yihE) that when knocked out confers hypersusceptibility to the lethal action of many antibacterial agents and other stresses. The product of the gene is a protein kinase that negatively regulates the MazF toxin endoribonuclease activity. Manipulation of yihE has allowed Zhao to show that bacteria self-destruct when challenged with harsh stress. He has also found that a ribosomal elongation factor, EF4, plays a destructive role when stress is harsh. Indeed, Zhao’s work has identified four factors (MazF, EF4, Cpx, and superoxide) that are dual function – at moderate levels of stress they protect cells, but at high levels of stress they assure death, largely through a cascade of reactive oxygen species. Small-molecule inhibitors and enhancers of lethal stress-response factors are expected to both facilitate antimicrobial action and broaden our knowledge of bacterial stress-response networks.

In a second line of work, performed in collaboration with Dr. Karl Drlica, Zhao has proposed, refined, and validated the mutant selection window hypothesis, a concept that provides a new paradigm for controlling antimicrobial resistance. The hypothesis explains in part how traditional antimicrobial dosing strategies lead to resistance and suggests new ways to severely restrict the acquisition of resistance. Dr. Zhao has directed tests in animal models of infection and a small clinical trial. The selection window hypothesis is also being used to guide antibiotic dosing regimens and the development of new antimicrobial agents.

The third line of work explores a novel, unconventional treatment of tuberculosis. The bacterium that causes tuberculosis has infected a third of world population and kills nearly 2 million people each year. Effective treatment regimens exist, but they often need to be rigidly implemented for 6 to 9 months with multiple types of chemotherapy. That often leads to serious patient non-compliance and the development of drug resistance. Indeed, the increasing prevalence of multi-drug resistance (MDR) and the emergence of extensive-drug resistance (XDR) tuberculosis may soon render all currently available treatments useless. Dr. Zhao has been studying the possibility of rapid eradication of the tubercle bacillus by perturbing the oxidative environment of the bacteria.

Selected Publications

Luan G, Hong Y, Drlica K, Zhao X (2017) Suppression of reactive-oxygen-species accumulation accounts for paradoxical bacterial survival at high quinolone concentration. Antimicrob Agents Chemother. PMI: 29229642

Hong Y, Li L, Luan G, Drlica K, Zhao X (2017) Contribution of reactive oxygen species to thymineless death in Escherichia coli. Nat Microbiol 2: 1667-1675. PMI: 28970486

Chang TL, Tasker C, Subbian S, Gao P, Couret J, Levine C, Ghanny S, Soteropoulos P, Zhao X, Landau N, Lu W (2017) Interferon epsilon protects primary macrophages against HIV infection. J Immunology 198: 158.115. PMI:

Zeng X, Li H, Zheng R, Kurepina N, Kreiswirth BN, Zhao X, Xu Y, Li Q (2016) Spoligotyping of Mycobacterium tuberculosis Complex Isolates by Use of Ligation-Based Amplification and Melting Curve Analysis. J Clin Microbiol 54: 2384-2387. PMI: 27335152

Tasker C, Subbian S, Gao P, Couret J, Levine C, Ghanny S, Soteropoulos P, Zhao X, Landau N, Lu W, Chang TL (2016) IFN-epsilon protects primary macrophages against HIV infection. JCI Insight 1: e88255. PMI: 27942584

Mi H, Wang D, Xue Y, Zhang Z, Niu J, Hong Y, Drlica K, Zhao X (2016) Dimethyl Sulfoxide Protects Escherichia coli from Rapid Antimicrobial-Mediated Killing. Antimicrob Agents Chemother 60: 5054-5058. PMI: 27246776

Malik M, Mustaev A, Schwanz HA, Luan G, Shah N, Oppegard LM, de Souza EC, Hiasa H, Zhao X, Kerns RJ, Drlica K (2016) Suppression of gyrase-mediated resistance by C7 aryl fluoroquinolones. Nucleic Acids Res 44: 3304-3316. PMI: 26984528

Liu Y, Zhou J, Qu Y, Yang X, Shi G, Wang X, Hong Y, Drlica K, Zhao X (2016) Resveratrol Antagonizes Antimicrobial Lethality and Stimulates Recovery of Bacterial Mutants. PLoS One 11: e0153023. PMI: 27045517

Zhao X, Hong Y, Drlica K (2015) Moving forward with reactive oxygen species involvement in antimicrobial lethality. The Journal of antimicrobial chemotherapy 70: 639-642. PMI: Medline:25422287

Long Q, Du Q, Fu T, Drlica K, Zhao X, Xie J (2015) Involvement of Holliday junction resolvase in fluoroquinolone-mediated killing of Mycobacterium smegmatis. Antimicrobial agents and chemotherapy 59: 1782-1785. PMI: Medline:25534729

Zhao X, Malik M, Hong Y, Drlica K (2014) Quinolones. Reference Module in Biomedical Research: 10.1016/B1978-1010-1012-801238-801233.802418-801231. PMI:

Zhao X, Drlica K (2014) Reactive oxygen species and the bacterial response to lethal stress. Current opinion in microbiology 21: 1-6. PMI: Medline:25078317

Yuan X, Liu Y, Bai C, Luo Y, Wang R, Wang R, Cai Y, Zhao X (2014) Mycoplasma pneumoniae infection is associated with subacute cough. The European respiratory journal 43: 1178-1181. PMI: Medline:24232705

Mustaev A, Malik M, Zhao X, Kurepina N, Luan G, Oppegard LM, Hiasa H, Marks KR, Kerns RJ, Berger JM, Drlica K (2014) Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding. The Journal of biological chemistry 289: 12300-12312. PMI: Medline:24497635

Malik M, Li L, Zhao X, Kerns RJ, Berger JM, Drlica K (2014) Lethal synergy involving bicyclomycin: an approach for reviving old antibiotics. The Journal of antimicrobial chemotherapy 69: 3227-3235. PMI: Medline:25085655

Li L, Hong Y, Luan G, Mosel M, Malik M, Drlica K, Zhao X (2014) Ribosomal elongation factor 4 promotes cell death associated with lethal stress. mBio 5: e01708. PMI: Medline:25491353

Mosel M, Li L, Drlica K, Zhao X (2013) Superoxide-mediated protection of Escherichia coli from antimicrobials. Antimicrob Agents Chemother. PMI: 23979754

Dorsey-Oresto A, Lu T, Mosel M, Wang X, Salz T, Drlica K, Zhao X (2013) YihE kinase is a central regulator of programmed cell death in bacteria. Cell Rep 3: 528-537. PMI: 23416055

Grant Support

Anaerobic shock as a novel treatment for tuberculosis ( NIH 1DP2OD007423-01, 9/30/2010-8/31/2015, PI

Novel fluoroquinolones for killing dormant Mycobacterium tuberculosis (NIH 1R01-AI 073491, 8/21/2012-7/31/2016, MPI (Drlica MPI))

New genes involved in cellular responses to quinolone treatment (NIH 1 R21 AI068014, 7/1/2007-6/30/2010, PI)

Anaerobic shock as a novel treatment for tuberculosis (Bill & Melinda Gates Foundation Grand Challenge Exploration Phase I with extension, 51963/OPP1008429, 10/1/2008-10/31/2010, PI)

Lethal action of fluoroquinolones with non-growing Mycobacterium tuberculosis (NIH 1R01-AI 073491, 5/15/2007-4/30/2012, Co-Investigator (Drlica PI))


Nankai University, China, B.S. 1988; Nankai University, China, M.S. 1990;
John Innes Centre, BBSRC/University of East Anglia, UK, Ph.D. 2003
Nankai University, China: 1991-1993 (Research Assistant Professor)
PHRI: 1994-present (Res. Scientist, Res. Associate Member, Principal Investigator)
Dept. Microbiol & Mol. Genet. N J Med. School-UMDNJ: 2006-2013 (Assist Prof., Assoc Prof.)
Dept. Microbiol. Biochem. Mol. Genet. N J Med Sch-Rutgers: 2013-present (Assoc Prof.)

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