Ying Kong, Ph.D.


Ying Kong, Ph.D.

Assistant Professor
858 Madison Ave.
401 Molecular Science Building
Memphis, TN 38163
Email: ykong3@uthsc.edu
Phone: 901-448-2465
Fax: 901-448-7360

 

Research Interests

Our laboratory is interested in:  1) tuberculosis pathogenesis; and 2) discovery of novel anti-tuberculosis therapeutics. With high morbidity and mortality, tuberculosis remains one of the biggest challenges to public health. The major causative pathogen of tuberculosis, Mycobacterium tuberculosis (Mtb), has an unusually slow growth rate. Quantifying Mtb with conventional colony forming unit (CFU) counting requires four weeks to have visible colonies present on the agar plates after plating. We have developed a variety of non-invasive optical in vivo imaging tools to study TB in animal models. By using non-invasive real-time imaging technologies to monitor TB in small animals, infections can be visualized within individual animals while images are collected. Combining these in vivo imaging tools with other cutting-edge in vitro technologies, we are studying and identifying bacterial and host factors affecting bacterial infection, survival, persistence, and reactivation. The results from these studies will contribute to development of improved diagnostic tools, anti-tuberculosis drugs, and vaccines.

  1. TB pathogenesis:

    Our laboratory has been working on identification of Mtb genes important for cell entry and intracellular survival, using a fluorescent imaging probe to label each mutant strain of Mtb from a mutant library. We now have a list of candidate genes that are involved in Mtb lipid metabolism and are critical for intracellular survival. We are investigating these genes’ functions and roles in TB pathogenesis.
  2. Development of anti-TB therapies from aurone analogues:

    Our laboratory has screened hundreds of synthetic aurone analogues and identified two aurones that have anti-TB effects in vitro and in vivo. We have analyzed the mechanism of these two aurones against Mtb, and have found that these two aurones inhibit Mtb chorismate synthase, which leads to reduction of aromatic amino acids. We are working on more aurone derivatives to identify compounds having higher efficacies against TB.

Figure 1
diagram

Vancomycin-Cy5.5 conjugate labeling dormant Mtb.A. Vancomycin-Cy5.5 conjugate labeling dormant Mtb smeared on slides. The Mtb strain was integrated with a tdTomato gene and was cultured in Wayne model to reach dormant status. It was then labeled with Vancomycin-Cy5.5. Red:Cy5.5; Green:tdTomato. B. Vancomycin-Cy5.5 conjugate labeling dormant Mtb in cells. After labeling the dormant Mtb strain with Vancomycin-Cy5.5 conjugate, it was loaded into the wells seeded with THP-1 cells and phagocytosed by the cells.

Figure 2

diagram

CNIR5 labeling non-replicating Mtb in vitro. A. CNIR5 label the non-replicating tdTomato-expressing Mtb CDC1551 strain smeared on slides. The non-replicating tdTomato-expressing Mtb strain was cultured in the Wayne model and then labeled with CNIR5 (carrying the Cy5.5 dye). B. The non-replicating Mtb in THP-1 macrophages labeled with CNIR5. The non-replicating tdTomato-expressing Mtb strain cultured in the Wayne model was used to infect PMA activated THP-1 cells, and then incubated with CNIR5. The tdTomato fluorescence is pseudo-colored green; CNIR5 fluorescence dye Cy5.5 is pseudo-colored red; and nuclei were stained with DAPI (blue).

Figure 3
figure

3-D IVIS in vivo images of i.v. Mtb infected mice at various time points post injection of CNIR800, a fluorogenic substrate of Mtb β-lactamase.

Selected Publications

  1. Lemieux MR, Siricilla S, Mitachi K, Eslamimehr S, Wang Y, Yang D, Pressly JD, Kong Y, Park F, Franzblau SG, Kurosu M. An antimycobacterial pleuromutilin analogue effective against dormant bacilli. Bioorganic & Medicinal Chemistry. 2018 July, https://doi.org/10.1016/j.bmc.2018.07.034
  2. Kong Y*, Cirillo JD. Fluorescence imaging of mycobacterial infection in live mice using fluorescent protein-expressing strains. Methods Mol. Biol. 2018;1790:75-85. PMID: 29858784 DOI: 10.1007/978-1-4939-7860-1_6. (*Corresponding author)
  3. H. Yang#, Y. Kong#, Y. Cheng#, H. Janagama, H. Hassounah, H. Xie, J. Rao, and J. D. Cirillo. Real time imaging of Mycobacterium tuberculosis using a novel near-infrared fluorescent substrate. J Infectious Diseases. 2017 Feb 1; 2015(3) 405-414.. PMID: 27421748 DOI: 10.1093/infdis/jiw298 (# Have contributed equally.)
  4. Yang, F. Ding, K. Mitachi, M. Kurosu, R. Lee, and Y. Kong*. A fluorescent probe for detecting Mycobacterium tuberculosis and identifying genes critical for cell entry. Front. Microbiol. 2016 Dec 20; 7: 2021. PMID:28066347; PMCID: PMC5168438. (*Corresponding author)
  5. Mitachi, S. Siricilla, D. Yang, Y. Kong, K. Skorupinska-Tudek, E. Swiezewska, S. G. Franzblau, and M. Kurosu. Fluorescence-based assay for polyprenyl phosphate-GlcNAc-1-phosphate transferase (WecA) and identification of a new WecA inhibitor that kills non-replicating Mycobacterium tuberculosis. Anal Biochem.2016 Nov 1;512:78-90. PMID: 27530653 PMCID: PMC5012913 DOI: 10.1016/j.ab.2016.08.008
  6. F. Nooshabadi, H. Yang, J. N. Bixler, Y. Kong, J. D. Cirillo, K. C. Maitland. Intravital fluorescence excitation in whole-animal optical imaging. PLoS One 2016 11(2): e0149932. doi:10.1371/journal.pone.0149932
  7. Y. Kong*, D. Yang, S. L. G. Cirillo, A. Akin, K. Francis, T. Maloney, and J. D. Cirillo*. Application of fluorescent protein expressing strains to evaluation of anti-tuberculosis therapeutic efficacy in vitro and in vivo.  PLoS One 2016 11(3): e0149972 doi:10.1371/journal.pone.0149972. (*Corresponding author)
  8. D. Yang and Y. Kong. The bacterial and host factors associated with extrapulmonary dissemination of Mycobacterium tuberculosis. Frontiers in Biology. 2015, 10(3): 252-261. (*Corresponding author)
  9. F. Ding and Y. Kong*. Host immune factors related to susceptibility to tuberculosis in animal models. J Immun Res. 2015;2(1): 1014. (*Corresponding author)
  10. Y. Cheng, H. Xie, P. Sule, H. Hassounah, E.A. Graviss, Y. Kong, J. D. Cirillo, and J. Rao. Fluorogenic Probes with substitutions at both the 2 and 7 positions of cephalosporin are highly BlaC-specific for rapid Mycobacterium tuberculosis detection. Angew Chem Int Ed Engl. 2014. Aug; (35) 9514-9518.
  11. H. Xie#, J. Mire#, Y. Kong#, M. Chang, H. Hassouna, J. C. Sacchettini, J. D. Cirillo & J. Rao. Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe. Nature Chemistry, 2012 Oct;4(10):802-9. doi: 10.1038/nchem.1435. Epub 2012 Sep 2. PMID:23000993. (#Have contributed equally.)
  12. Y. Zhou, A. Torres, L. Chen, Y. Kong, J.D. Cirillo, and H. Liang, Fluid-shear method to evaluate bacterial adhesion to glass surfaces. Journal of Applied Physics. 2012 112, 014703; http://dx.doi.org/10.1063/1.4733685.
  13. Y. Zhou, Y. Kong, S. Kundu, J.D. Cirillo, and H. Liang. Antibacterial activities of gold and silver nanoparticles against Escherichia coli and Bacillus Calmette-Guérin. Journal of Nanobiotechnology, 2012, May 6;10(1):19. PMID:22559747
  14. N. Mufti#, Y. Kong#, J.D. Cirillo, and K.C. Maitland. Fiber optic microendoscopy for preclinical study of bacterial infection dynamics. Biomed. Opt. Express, Vol. 2, Issue 5, pp. 1121-1134 (2011) (#Have contributed equally.) PMCID: PMC3087570, PMID:21559125
  15. Y. Kong, A.R. Akin, K.P. Francis, N. Zhang, T.L. Troy, J. Rao, S.L.G. Cirillo, and J.D. Cirillo. Whole body imaging of infection using fluorescence. Curr. Protoc. Microbiol. 2011 May, Chapter 2: Microscopy and Imaging. Section C: Other Imaging Methods. 2C.3.1–2C.3.21.
  16. Y. Kong, Y. Shi, M. Chang, A.R. Akin, K.P. Francis, N. Zhang, T.L. Troy, S.L.G. Cirillo, and J.D. Cirillo. Whole body imaging of infection using bioluminescence. Curr. Protoc. Microbiol. 2011 May, Chapter 2: Microscopy and Imaging. Section C: Other Imaging Methods 2C.4.1–2C.4.17.
  17. Y. Feng, Y. Kong*, P.F. Barnes, F. Huang, P. Klucar, X. Wang, B. Samten, M. Sengupta, B. Machona, R. Donis, A.R. Tvinnereim, and H. Shams. Exposure to cigarette smoke inhibits the pulmonary T cell response to influenza and Mycobacterium tuberculosis. Infect. Immun. 2011 January, 79 (1):  229-237. (*Have contributed equally.) PMID:20974820
  18. Y. Kong and J.D. Cirillo. Reporter enzyme fluorescence (REF) imaging and quantification of tuberculosis in live animals. Virulence, 2010 November/December, 1(6): 558-62. PMID: 21178505
  19. Y. Kong, H. Yao, H. Ren, S. Subbian, S.L.G. Cirillo, J.C. Sacchettini, J. Rao, and J.D. Cirillo. Imaging tuberculosis with endogenous β-lactamase reporter enzyme fluorescence in live mice. Proc Natl Acad Sci U S A., 2010 Jul 6;107(27):12239-44. PMCID: PMC2901431, PMID: 20566877 (“Exceptional Article” Faculty 1000)
  20. Y. Kong, S. Subbian, S.L.G. Cirillo, J.D. Cirillo. Application of optical imaging to study extrapulmonary spread by tuberculosis. Tuberculosis. 2009 S, S15-S17. PMID:20006298
  21. Klucar, P.F. Barnes, Y. Kong, S.T. Howard, X. Pang, F. Huang, A.R. Tvinnereim, B. Samten, H. Shams. Vaccination strategies to enhance local immunity and protection against Mycobacteriun tuberculosis.Vaccine. 2009 Mar 13;27(12):1816-24. PMCID: PMC2768422, PMID: 19402204
  22. P. Klucar, P.F. Barnes, Y. Kong, B. Samten, A. Tvinnereim, R. Spallek, GT. Nepom, M. Singh, H. Shams. Characterization of effector functions of human peptide-specific CD4+ T-cell clones for an intracellular pathogen. Hum Immunol. 2008 Aug;69(8):475-83. PMID: 18588932
  23. Y. Kong, M.D. Cave, L. Zhang, B. Foxman, C.F. Marrs, J.H. Bates, and Z. Yang. Association between Mycobacterium tuberculosis Beijing/W lineage strain infection and extrathoracic tuberculosis: insight from epidemiologic and clinical characterization of the three principal genetic groups of M. tuberculosis clinical isolates. J. Clin. Microbio. 2007 Feb;45(2):409-14. PMCID: PMC1829078, PMID: 17166963
  24. Y. Kong, M.D. Cave, L. Zhang, B. Foxman, C.F. Marrs, J.H. Bates, and Z. Yang. A population-based study of deletions in five different genomic regions of Mycobacterium tuberculosis and their possible clinical relevance. J. Clin. Microbio. 2006, Nov; 44(11):3940-6 PMCID: PMC1698370, PMID: 16957037
  25. Y. Kong, M.D. Cave, D. Yang, L. Zhang, C.F. Marrs, B. Foxman, J.H. Bates, F. Wilson, L.N. Mukasa, and Z. Yang. Distribution of insertion and deletion associated genetic polymorphisms among four Mycobacterium tuberculosis phospholipase C genes and associations with extra-thoracic tuberculosis: a population-based study. J. Clin. Microbio. 2005, Dec 43: 6048-6053. PMCID: PMC1317199, PMID: 16333097.

Education

  • PhD – University of Michigan
  • Postdoc – University of Texas Health Science Center; Texas A&M Health Science Center