Research Interests:
- Type III secretion system of Pseudomonas aeruginosa.
- Apoptotic pathway triggered by ExoS.
- Membrane impermeability mediated multidrug resistance.
- Sensitive detection of pathogens, toxins and chemicals.
Pseudomonas aeruginosa causes a wide range of infections, from minor skin infections to serious and sometimes life-threatening complications. P. aeruginosa is a causative agent of systemic infections in immunocompromised patients such as those receiving chemotherapy, elderly patients and burn victims. In special groups of patients, P. aeruginosa can also cause localized infections, particularly in the lungs of cystic fibrosis patients and corneals of certain contact lens users.
Type III secretion system (T3SS) is encoded by various animal and plant pathogens. It encodes over 30 proteins that assemble into a “needle” complex designed to deliver bacterial proteins directly into the cytoplasmic compartment of eukaryotic cells. In animal pathogens, the principle function of T3SS is to deliver anti-host-virulence-determinants into mammalian cells, thus evading host immune attack.
The T3SS of P. aeruginosa responds to various environmental signals such as low calcium, direct contact with mammalian cells and various environmental stresses. There are four known effector molecules that are secreted through the T3SS of P. aeruginosa, including ExoS, ExoT, ExoY and ExoU. The ADP-ribosyltransferase activity of ExoS is known to cause programmed cell death in various types of mammalian cells.
We are interested in understanding the regulatory mechanism by which the T3SS genes are regulated during various stages of host infections. Furthermore, how does the translocated bacterial protein (ExoS) initiates apoptosis in host cells. Eventually, we hope to utilize the bacterial ability to trigger host cell apoptosis in cancer therapy.
Decreased membrane permeability often results in multidrug resistance. Interestingly, P. aeruginosa seems to be able to regulate its own membrane permeability through a response regulator system. We are interested in understanding the regulatory mechanism to counter multidrug resistant P. aeruginosa in various human infections.
In collaboration with chemists and engineers, we are also involved in the development of sensitive detection devices for various pathogens, toxins and chemicals.
Recent Publications: (2003-July, 2005)
Lian, W., D. Wu, D. V. Lim and S. Jin. (2005) Sensitive detection of multiplex toxins using antibody microarray. (in preparation).
Jia, J., Y. Wang and S. Jin. (2005) ExoS of Pseudomonas aeruginosa is sufficient to trigger apoptosis. (in preparation).
Alaoui-El-Azher, M., J. Jia, W. Lian and S. Jin. (2005) ExoS of Pseudomonas aeruginosa induces Apoptosis through a Fas receptor/Caspase 8-independent pathway in HeLa cells. Cellular Microbiology (submitted).
Qian, M., C. K. Fredrickson, S. Jin and Z. H. Fan. (2005) Toxin detection by miniaturized in vitro protein expression array. Analytical Chemistry. (in press).
Kim, J., K. Ahn, S. Min, J, Jia, U. Ha, D. Wu and S. Jin. (2005) Factors triggering type III secretion in Pseudomonas aeruginosa. Microbiology (in press).
Wu, W., and S. Jin. (2005) PtrB of Pseudomonas aeruginosa Suppresses Type III Secretion System Under the Stress of DNA Damage. Journal of Bacteriology (in press)
Zhao, X., L. R. Hillard, S. J. Mechery, Y. Wang, R. P. Bagwe, S. Jin and W. Tan. (20004) A rapid bioassay for single bacterial cell quantitation using bioconjugated nanoparticles. Proceedings of National Academy of Science USA. 101:15027-32.
Wu, W., H. Badrane, S. Arora, H. V. Baker and S. Jin. (2204) MucA-mediated coordination of type III secretion and alginate synthesis in Pseudomonas aeruginosa. Journal of Bacteriology 186:7575-85.
Lian, W., S. A. Litherland, H. Badrane, W. Tan, D. Wu, H. V. Baker, P. A. Gulig, D. V. Lim and S. Jin. (2004) Ultrasensitive detection of biomolecules with fluorescent dye-doped nanoparticles. Analytical Biochemistry. 334:135-44.
Jung, Y., Y. Gu, D. Wu and S. Jin. (2004) Mutants of Agrobacterium tumefaciens virG gene that activate transcription of vir promoter in Escherichia coli. Current Microbiology 49:334-40.
Ha, U., J. Kim, H. Badrane, J. Jia, H. V. Baker, D. Wu and S. Jin. (2004). An in vivo Inducible Gene of Pseudomonas aeruginosa Encodes an Anti-ExsA to Suppress the Type III Secretion System. Molecular Microbiology 54:307-20.
Govindasamy, L., T. Kukar, W. Lian, B. Pedersen, Y. Gu, M. Agbandje-McKenna, S. Jin, R. McKenna and D. Wu.(2004) Structural and mutational Characterization of L-Carnitine Binding to Human Carnitine Acetyltransferase. Journal of Structural Biology 146:416-424.
Lian, W., Y,.Gu, B. Pedersen, T. Kukar, L. Govindasamy, M. Agbandje-McKenna, S. Jin, R. McKenna and D. Wu. (2004) Crystallization and Preliminary X-ray Crystallographic Studies on Recombinant Rat Choline Acetyltransferase. Acta Crystallograpica. D60:374-75.
Gordon E. S, C. H. Gilliam, S. Jin, C. K. Cavenaugh, R. W. Hall, R. W. Bradsher and R. F. Jacobs. (2004) Use of DNA fingerprinting in decision making for considering closure of neonatal intensive care units because of Pseudomonas aeruginosa bloodstream infections.. The Pediatric Infectious Disease Journal 23:110-4.
Ahn, K., U. Ha, J. Jia, D. Wu and S. Jin. (2004) The truA gene of Pseudomonas aeruginosa is required for the expression of type III secretory genes. Microbiology 150:539-47.
Zeng, L. and S. Jin. (2003) aph(3’)-IIb, a gene encoding an aminoglycoside-modifying enzyme, is under the positive control of a surrogate regulator HpaA. Antimicrobial Agents and Chemotherapy. 47:3867-76..
Jia, J., M. Alaoui-El-Azher, M. Chow, T. C. Chambers, H. Baker and S. Jin (2003) c-Jun NH2-terminal kinase-mediated signaling is essential for Pseudomonas aeruginosa ExoS-induced apoptosis. Infection and Immunity. 71:3361-70
Ha, U., Y. Wang and S. Jin. (2003) DsbA of Pseudomonas aeruginosa is Essential for Multiple Virulence Factors. Infection and Immunity 71:1590-5.
Wang, Y., U. Ha, L. Zeng and S. Jin. (2003) Regulation of membrane permeability by a two component regulatory system in Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 47:95-101.
