Molecular Mycobacteriology Research Unit

Director: Prof Valerie Mizrahi
E-mail: valerie.mizrahi@wits.ac.za

Tuberculosis (TB) is one of leading causes of infectious deaths in the world, claiming approximately 3 million lives per annum. In addition, 8 million new cases of TB are identified every year.

TB is caused by the bacterium, Mycobacterium tuberculosis, a formidable pathogen which has infected about one third of the world's population. The variable efficacy of the BCG vaccine, combined with alarming increases in the levels of resistance to existing anti-TB drugs, has underscored the need to develop new tools for the prevention and treatment of this devastating disease.

It is against this background that the Molecular Mycobacteriology Research Unit (MMRU) was established in 2000 as a three-way partnership between the MRC, the National Health Laboratory Services (NHLS) and the University of the Witwatersrand (Wits). Since 2004, the MMRU has also served as the Wits/NHLS node of the DST/NRF Centre of Excellence for Biomedical TB Research.

The original mission of the MMRU was to develop and apply genetic tools for the identification, validation and characterisation of novel drug targets and vaccine candidates for tuberculosis. By adopting a research strategy that is based on investigating specific aspects of the physiology and metabolism of M. tuberculosis, the MMRU has positioned itself at the front-end of TB drug discovery research.

Specific areas of interest include:

• Mechanisms of DNA repair, replication and mutagenesis in mycobacteria, as applied specifically to inter-strain variation and the evolution of drug resistance;
• The role of resuscitation-promoting factors (Rpfs) in growth, culturability, resuscitation and virulence of M. tuberculosis;
• The biosynthesis and transportation of vitamin B12 and its role in myobacterial metabolism;
•  Respiration and electron transport in mycobacteria;
• Mechanisms of stress adaptation and antibiotic tolerance in mycobacteria; and
• The development of new tools for TB drug discovery.

All of these areas encompass aspects of M. tuberculosis physiology of greatest relevance to TB drug discovery, namely, drug resistance, persistence and tolerance/indifference.

The MMRU is funded by grants from the National Research Foundation, Wits, the Seattle Biomedical Research Institute and an International Research Scholars' Grant from the Howard Hughes Medical Institute (to Prof Mizrahi).