Yang, Ching-Hong
chyang@uwm.eduLapham Hall Lap131D

Yang, Ching-Hong

Milwaukee Institute for Drug Discovery (MIDD)

Professor of Biological Sciences and Microbiology

Research Area

Development of antibiotic alternatives for disease treatment and preventions. With the rise of antibiotic resistance, it is crucial to be creative and find new ways of harnessing undiscovered antimicrobials. Virulence inhibitors (VIs) are compounds that inhibit the expression of virulence genes but do not affect the survival of bacterial pathogens. Thus, there is no direct selective pressure for bacteria to mutate to resist the virulence inhibitors compared to traditional antibiotics. However, as virulence genes are essential for the pathogens to cause infection, “shutting off” the virulence genes can effectively prevent disease from occurring. Additionally, unlike antibiotics that kill both pathogens and non-pathogens without any selection, virulence inhibitors only target the pathogens that contain the virulence genes and thus do not affect the non-pathogenic environmental bacteria. The target specificity of VIs further reduces the likelihood of resistance development and spread.

Organic agricultural production in the United States is challenged by the lack of adequate organic disease control measures. Antibiotic sprays of streptomycin and oxytetracycline (used for human medicine) are one of the few options that can effectively suppress bacterial diseases in commercial orchards. This puts an urgent need to develop new control strategies for both organic and conventional growers. Biopesticides are classified as the pesticides derived from natural materials such as animals, plants, microbes, or a synthetic version of something naturally occurring that is structurally similar and functionally identical.  We use a method called ‘PROMISA’ that uses the conditions that mimic the natural environment to grow and isolate the microbes from nature.  Natural metabolites were identified for their use in disease management. The aims of this study are to identify novel, potent, new antibiotics, develop selective virulence inhibitors, and study the effect of these antimicrobials on key targets of the bacterial pathogens.

 Novel approaches to study microbial ecology using microbial diversity profiling. The quantitative description of microbial communities is one of the most promising areas of research in microbial ecology. New techniques in molecular ecology have now opened the door for revolutionary advances in our understanding of microbial communities in nature as well as the identification of new microorganisms and microbial products that can be harnessed for biotechnology. We have been especially interested in developing novel approaches to analyze microbial diversity that are associated with plants. Our most recent work focuses on interactions between plants and microorganisms using 16S and 18S rDNA profiling.

Application of functional genomic tools to investigate microbial gene expression in different environments. With the availability of complete genome sequences of different microorganisms, functional genomic tools provide a powerful approach for identifying microbial genes that are expressed during the association of bacteria with their hosts in response to various environmental factors. Techniques we are using include a custom-designed microarray, fluorescence-activated cell sorting, and bioinformatic tools to explore genes of bacterial pathogens that are involved in type III secretion regulon and pathogenesis.

Selected publication

  1. Yuan X, Yu M, Yang CH. Innovation and Application of the Type III Secretion System Inhibitors in Plant Pathogenic Bacteria. Microorganisms. 2020 Dec 9;8(12):1956.
  2. Yuan X, Zeng Q, Xu J, Severin GB, Zhou X, Waters CM, Sundin GW, Ibekwe AM, Liu F, Yang CH. 2020. Tricarboxylic Acid (TCA) Cycle Enzymes and Intermediates Modulate Intracellular Cyclic di-GMP Levels and the Production of Plant Cell Wall-Degrading Enzymes in Soft Rot Pathogen Dickeya dadantii. Mol Plant Microbe Interact 33:296-307.
  3. Han Z, Ma J, Yang CH, Ibekwe AM. 2020. Soil salinity, pH, and indigenous bacterial community interactively influence the survival of E. coli O157:H7 revealed by multivariate statistics. Environ Sci Pollut Res Int doi:10.1007/s11356-020-10942-6.
  4. Yuan X, Zeng Q, Khokhani D, Tian F, Severin GB, Waters CM, Xu J, Zhou X, Sundin GW, Ibekwe AM, Liu F, Yang CH. 2019. A feed-forward signalling circuit controls bacterial virulence through linking cyclic di-GMP and two mechanistically distinct sRNAs, ArcZ and RsmB. Environ Microbiol 21:2755-2771.
  5. Cui Z, Yang CH, Kharadi RR, Yuan X, Sundin GW, Triplett LR, Wang J, Zeng Q. 2019. Cell-length heterogeneity: a population-level solution to growth/virulence trade-offs in the plant pathogen Dickeya dadantii. PLoS Pathog 15:e1007703.
  6. Yuan X, Tian F, He C, Severin GB, Waters CM, Zeng Q, Liu F, Yang CH. 2018. The diguanylate cyclase GcpA inhibits the production of pectate lyases via the H-NS protein and RsmB regulatory RNA in Dickeya dadantii. Mol Plant Pathol 19:1873-86.
  7. Li L, Ma J, Mark Ibekwe A, Wang Q, Yang C-H. 2018. Influence of Bacillus subtilis B068150 on cucumber rhizosphere microbial composition as a plant protective agent. Plant and Soil 429:519-531.
  8. Cui Z, Yuan X, Yang CH, Huntley RB, Sun W, Wang J, Sundin GW, Zeng Q. 2018. Development of a Method to Monitor Gene Expression in Single Bacterial Cells During the Interaction With Plants and Use to Study the Expression of the Type III Secretion System in Single Cells of Dickeya dadantii in Potato. Front Microbiol 9:1429.
  9. Patel RR, Sundin GW, Yang CH, Wang J, Huntley RB, Yuan X, Zeng Q. 2017. Exploration of Using Antisense Peptide Nucleic Acid (PNA)-cell Penetrating Peptide (CPP) as a Novel Bactericide against Fire Blight Pathogen Erwinia amylovora. Front Microbiol 8:687.
  10. Fan S, Tian F, Li J, Hutchins W, Chen H, Yang F, Yuan X, Cui Z, Yang CH, He C. 2017. Identification of phenolic compounds that suppress the virulence of Xanthomonas oryzae on rice via the type III secretion system. Mol Plant Pathol 18:555-568.
  11. Yu C, Wang N, Wu M, Tian F, Chen H, Yang F, Yuan X, Yang CH, He C. 2016. OxyR-regulated catalase CatB promotes the virulence in rice via detoxifying hydrogen peroxide in Xanthomonas oryzae pv. oryzae. BMC Microbiol 16:269.
  12. Sundin GW, Castiblanco LF, Yuan X, Zeng Q, Yang CH. 2016. Bacterial disease management: challenges, experience, innovation and future prospects: Challenges in Bacterial Molecular Plant Pathology. Mol Plant Pathol 17:1506-1518.
  13. Yuan X, Khokhani D, Wu X, Yang F, Biener G, Koestler BJ, Raicu V, He C, Waters CM, Sundin GW, Tian F, Yang CH. 2015. Cross-talk between a regulatory small RNA, cyclic-di-GMP signalling and flagellar regulator FlhDC for virulence and bacterial behaviours. Environ Microbiol 17:4745-63.
  14. Li Y, Hutchins W, Wu X, Liang C, Zhang C, Yuan X, Khokhani D, Chen X, Che Y, Wang Q, Yang CH. 2015. Derivative of plant phenolic compound inhibits the type III secretion system of Dickeya dadantii via HrpX/HrpY two-component signal transduction and Rsm systems. Mol Plant Pathol 16:150-63.
  15. Khokhani D, Zhang C, Li Y, Wang Q, Zeng Q, Yamazaki A, Hutchins W, Zhou SS, Chen X, Yang CH. 2013. Discovery of plant phenolic compounds that act as type III secretion system inhibitors or inducers of the fire blight pathogen, Erwinia amylovora. Appl Environ Microbiol 79:5424-36.