Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, continues to be a worldwide public health problem. WHO estimates that over one third of the world's population, 1.7 billion people, are infected with M. tuberculosis. There are 8 million new cases and 3 million deaths from tuberculosis annually. In recent years, the incidence of tuberculosis has been increasing worldwide as patients with AIDS are highly susceptible to M. tuberculosis infections. Infection with conventional M. tuberculosis strains can effectively be cured with a combination of anti-tuberculosis drugs. Multidrug resistant (MDR-TB) strains have emerged in several countries with case fatality ranging from 4O-6O% in immunocompetent individuals and >8O% in immunocompromised individuals. Key to any successful control and eradication efforts will be the acquisition of basic knowledge regarding the genetics, biochemistry and physiology of M. tuberculosis cells. In the past few years, a number of systems have been developed that permit gene transfer in mycobacterial species. The focus of this proposal is to use these genetic systems in order to define mechanisms by which quinolone antibiotics interact with M. tuberculosis so as to build a knowledge base to design novel quinolones with anti-M. tuberculosis activities.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI035170-02
Application #
3747533
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Type
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

Sharp, P M; Bailes, E; Robertson, D L et al. (1999) Origins and evolution of AIDS viruses. Biol Bull 196:338-42
Gao, F; Robertson, D L; Carruthers, C D et al. (1998) A comprehensive panel of near-full-length clones and reference sequences for non-subtype B isolates of human immunodeficiency virus type 1. J Virol 72:5680-98
Gao, F; Robertson, D L; Carruthers, C D et al. (1998) An isolate of human immunodeficiency virus type 1 originally classified as subtype I represents a complex mosaic comprising three different group M subtypes (A, G, and I). J Virol 72:10234-41
Soares, M A; Robertson, D L; Hui, H et al. (1997) A full-length and replication-competent proviral clone of SIVAGM from tantalus monkeys. Virology 228:394-9
Salminen, M O; Carr, J K; Robertson, D L et al. (1997) Evolution and probable transmission of intersubtype recombinant human immunodeficiency virus type 1 in a Zambian couple. J Virol 71:2647-55
Scheirer, K E; Higgins, N P (1997) The DNA cleavage reaction of DNA gyrase. Comparison of stable ternary complexes formed with enoxacin and CcdB protein. J Biol Chem 272:27202-9
Gao, F; Robertson, D L; Morrison, S G et al. (1996) The heterosexual human immunodeficiency virus type 1 epidemic in Thailand is caused by an intersubtype (A/E) recombinant of African origin. J Virol 70:7013-29
Gao, F; Morrison, S G; Robertson, D L et al. (1996) Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G. The WHO and NIAID Networks for HIV Isolation and Characterization. J Virol 70:1651-67
Salazar, L; Fsihi, H; de Rossi, E et al. (1996) Organization of the origins of replication of the chromosomes of Mycobacterium smegmatis, Mycobacterium leprae and Mycobacterium tuberculosis and isolation of a functional origin from M. smegmatis. Mol Microbiol 20:283-93
Renau, T E; Sanchez, J P; Gage, J W et al. (1996) Structure-activity relationships of the quinolone antibacterials against mycobacteria: effect of structural changes at N-1 and C-7. J Med Chem 39:729-35

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