The primary foci of my research program include to understand pathogenesis of Escherichia coli in diarrheal disease at the molecular level and to develop effective prevention against diarrheal disease in humans and livestock animals. Diarrheal E. coli particularly enterotoxigenic E. coli (ETEC) strains, those E. coli strains produce enterotoxins, are the leading bacteria causing diarrhea, a disease continue to be the second leading cause of death to children younger than 5 years from the developing countries and a major threat to global health. ETEC strains cause about 500 million diarrhea cases each year among children that result in annual deaths of 300,000 – 500,000, mostly children younger than 5 years. Repeated diarrhea in children is associated with line-long malnourishment and lagged physical and intellectual development. In addition, ETEC strains are the most common cause of traveler’s diarrhea (400 million cases annually). ETEC are also the primary cause of diarrhea in livestock animals. Neonatal diarrhea and post-weaning diarrhea are among the most important diseases in livestock animals and cause substantial economic losses to livestock producers worldwide. In this laboratory, we develop multiplex PCR markers to study ETEC molecular epidemiology, apply an additive model and molecular biology techniques to determine role(s) played by individual genes or molecules, particularly heat-labile toxin (LT) and heat-stable toxin (ST) and bacterial adhesins, in ETEC associated diarrhea disease thus to identify disease virulence determinants, characterize interaction between bacterial adhesin(s) and host receptors to understand host-pathogen interaction, explore genetic fusion antigens to develop toxoid and toxoid-adhesin multivalent vaccines against ETEC diarrhea, and use a gnotobiotic piglet challenge model to evaluate candidate vaccine protective efficacy. In addition, we identify and construct molecules to serve as an antigen delivery vector but also an adjuvant for general vaccine development against bacterial and viral infectious diseases. My research is largely supported by NIH, USDA/AES, National Pork Board, and private found agencies such as EVI/PATH/Bill & Melinda Gates Foundation.
Publications (Selected from 46 peer-reviewed publications; * indicates corresponding author)
Ruan, X., and W. Zhang* . 2013. Oral immunization of a live attenuated Escherichia coli strain expressing a holotoxin-structured adhesin-toxoid fusion (1FaeG-FedF-LTA2:5LTB) protected young pigs against enterotoxigenic E. coli (ETEC) infection. Vaccine 31:1470-1475.
Hashish, E., C. Zhang, X. Ruan, D. E. Knudsen, C. C. Chase, E. E. Isaacson, G. Q. Zhu, and W. Zhang*. 2013. A multiepitope fusion antigen elicits neutralizing antibodies against enterotoxigenic Escherichia coli and homologous bovine viral diarrhea virus in vitro. Clin. Vaccine Immun. 20(7):1076-1083.
*Zhang, W., and D. A. Sack. 2012. Progress and hurdles in the development of vaccines against
enterotoxigenic Escherichia coli in humans. Expert Rev. Vaccines. 11(6):1-18.
Ruan X., Crupper S.C., Schultz B.D., Robertson D.C., and W. Zhang*. 2012.; Escherichia coli expressing enteroaggregative heat-stable toxin 1 (EAST1) did not cause an increase of cAMP or cGMP levels in cells, and no diarrhea in 5-day old gnotobiotic pigs. PLoS ONE. 7(8):e43203.
Liu, M., X. S. Ruan, C. Zhang, S. Lawson, D. Knudsen, J. P. Nataro, D. C. Robertson, and W. Zhang*. 2011. Heat-labile (LT) and heat-stable (STa) toxoid fusions (LTR192G-STaP13F) of human enterotoxigenic scherichia coli elicited neutralizing antitoxin antibodies. Infect. Immun. 79(10): 4002-4009
Ruan, X., M. Liu, T. Casey, and W. Zhang*. 2011. A tripartite fusion, FaeG-FedF-LT192A2:B, of enterotoxigenic Escherichia coli (ETEC) elicits antibodies neutralizing CT Toxin, inhibiting adherence of K88 (F4) and F18 Fimbriae, and protecting pigs against K88ac/LT ETEC infection. Clin. Vaccine Immun. 18(10):1593-1599.
Liu M., C. Zhang, K. Meteo, JP Nataro, DC Robertson, and W. Zhang*. 2011. Modified heat-stable toxins (hSTa) of enterotoxigenic Escherichia coli lose toxicity but display antigenicity after being genetically fused to heat-labile toxoid LT(R192G). Toxins. 3:1146-1162.
Zhang, C, and W. Zhang*. 2010.Escherichia coli K88ac fimbriae expressing heat-labile (LT) and heat- stable (STa) toxin epitopes elicit antibodies that neutralize cholerae toxin and STa toxin and inhibit adherence of K88ac fimbrial E. coli.Clin. Vaccine Immun. 1859-1867.
*Zhang, W. and D. H. Francis. 2010. Genetic fusions of heat-labile toxoid (LT192) and heat-stable toxin b (STb) of porcine enterotoxigenic Escherichia coli (ETEC) elicit protective anti-LT and anti-STa antibodies. Clin.Vaccine Immun.17(8):1223-1231.
*Zhang, W. , C. Zhang, D. H. Francis, J. Nataro, and D. C. Robertson. 2010.Genetic fusions of pLTAB and pSTa toxoids of enterotoxigenic Escherichia coli (ETEC) induce protective anti-LT and anti-STa antibodies.Infect. Immun.78(1):316-325.
Zhang, C., D. Rausch, and W. Zhang*. 2009. Heat-labile and heat-stable toxin genes of enterotoxigenic Escherichia coli strains isolated from diarrheal pigs show little heterogeneity. Appl. Environ. Micorbiol. 75(19):6402-6405
*Zhang, W. , Y. Fang, and D. H. Francis. 2009. Characterizing the binding specificity of K88ac and K88ad fimbriae of enterotoxigenic Escherichia coli by constructing K88ac/ad chimeric FaeG major subunits. Infect. Immun. 77:699-706.
*Zhang, W., D. Robertson, C. Zhang, W. Bai, M. Zhao, and D. Francis. 2008. Escherichia coli constructs expressing human or porcine enterotoxins induce identical diarrheal diseases in a piglet infection model. Appl. Environ. Microbiol.74:5832-5837.
*Zhang, W., M. Zhao, L. Ruesch, A. Omot, and D. Francis.2007. Prevalence of virulence factors of Escherichia coli strains isolated from pigs with post-weaning diarrhea. Vet. Microbiol. 123:145-152.
*Zhang, W., E. Berberov, J. Freeling, D. He, R. Moxley, and D. Francis*.2006. Significance of heat stable and heat-labile enterotoxins in porcine colibacillosis --- An additive model for pathogenicity studies.Infect & Immun. 74:3107-3114.