Molecular Mycobacteriology Research Unit

Research highlights

In a paper published recently in Molecular Microbiology, MMRU researchers and collaborators in the US, Russia and the UK reported the construction of mutant strains of Mycobacterium tuberculosis lacking all five resuscitation-promoting factor (rpf) genes. These strains and their progenitors have provided an important resource for investigating the relationship between the microbiological properties of dormancy, non-culturablility and resuscitation in Mycobacterium tuberculosis, and the clinically defined phenomena of latent tuberculosis infection and reactivation disease.

In another significant development, studies carried out by scientists in the MMRU and published in the Journal of Bacteriology have yielded intriguing new insights into the biosynthesis of the essential cofactor, cobalamin (vitamin B12), in mycobacteria and the function of vitamin B12-dependent enzymes and pathways in these organisms. Some of these findings have potentially important implications for tuberculosis drug discovery. This study formed the basis of a large, three-year research grant from the Swiss/South Africa Joint Research Programme grant awarded jointly to Prof. Mizrahi and Prof. John McKinney (École Polytechnique Fédérale de Lausanne, Switzerland), which will support research activities in both the Swiss and South African laboratories.

As part of an ongoing study on mechanisms of DNA metabolism in Mycobacterium tuberculosis, researchers at the Wits node have investigated the function of genes encoding subunits of ribonucleotide reductase (RNR), an enzyme which catalyzes the first committed step in DNA replication by providing the building blocks required for DNA synthesis. In a paper published in the Journal of Bacteriology, scientists in the MMRU identify a potential vulnerability in dNTP provision in mycobacteria. Based on the evidence arguing against specialist roles for alternate, RNR small subunits in the provision of dNTPs for DNA synthesis of M. tuberculosis in vivo, the results of this study offer a compelling rationale for pursuing the essential class Ib RNR as a target for anti-tubercular drug discovery.    

In other highlights, the Director of the MMRU, Prof Mizrahi, was elected into fellowship of the American Academy of Microbiology. She co-organized the Keystone Symposium on Pathogenesis and Control of Emerging Infections and Drug Resistant Organisms, held in Bangkok, Thailand, in October 2008. Prof Mizrahi was also appointed to a three-year term on the Scientific Advisory Committee of the Global Alliance for TB Drug Development, which is based in New York. Dr. Bavesh Kana was granted a Career Development Award from the MRC and also received the Best Oral Presentation Prize in the Infectious Disease section of the Faculty of Health Sciences 2008 Research Day.