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Tianyu Zhang, PhD
Post doctoral Fellow
Latent tuberculosis infection (LTBI- the initial infection of TB develops under the pressure of host immunity into a paucibacillary latent state which may reactivate into clinical disease at a later time.) is a very serious a problem in the world. It is estimated that one-third of the world's population is infected with Mycobacterium tuberculosis, but that only 10% of infected people break down with the disease. Treatment of LTBI requires a long period of chemotherapy (9-month course of therapy with INH alone or a regimen using rifampin alone for 4 months), which makes treatment-compliance extremely difficult. So, to find a good regiment to cure LTBI is very urgent. However, there is no very good animal model of LTBI until now, which hampered the study of LTBI treatment seriously. My object is to develop a satisfactory cost-effective, highly reproducible and time-saving mouse model of LTBI. In addition, the model can be used to identify genes involved in LTBI formation by testing known TB mutants.
The Mycobacterium tuberculosis genome analysis reveals a lot of genes encoding putative drug efflux pumps. During the course of tuberculosis chemotherapy many of these pumps might play a role in the survival of the mycobacterial populations. Recent reports have suggested that efflux pumps may be involved in transporting isoniazid, one of the main drugs used to treat tuberculosis. The active efflux pumps in mycobacteria may increase in number and activity rendering wild-type mycobacteria increasingly resistant to a given antibiotic. This could be a mechanism by which mutated resistant strains become better fit to the selective environment and in chemotheorapy some TB bacilli with higher efflux activity can persist longer and better. Compounds capable of inactivating these pumps could improve anti-tuberculous therapeutics. We have found some transposon-TB mutants with efflux genes mutated are more sensitive to some widely used drugs. Further study is being carried out.
In addition, Mycobacterium ulcerans is a slow growing (a colony can be seen in about 1 and a half months on the plate) pathogenic bacterium which can cause Buruli ulcer. I have created some engineered luminescent M. ulcerans strains with luciferase as a biomarker. The strains may be very useful in chemotherapy study and in drug screening.
1 Zhang T, Wang L, Xu G, et al. Disruption of the ste22 gene encoding a glycosyltransferase and its function in biosynthesis of Ebosin in Streptomyces sp. 139. Curr Microbiol, 2006,52:55-9.
2 Zhang T, Wang L, Xu G, et al. Disruption of ste23 gene affects composition profile and bioactivity of exopolysaccharide produced by Streptomyces sp. 139. Lett Appl Microbiol, 2006,42:132-7.
3 Zhang TY, Wang LY, Jiang R, et al. [Cloning and expression of UDP-glucose-4- epimerase gene from Streptomyces and characteristics of the enzyme]. Acta Microbiologica Sinica , 2005,45:881-4.