Molecular Mycobacteriology Research Unit

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

Tuberculosis (TB) is one of the leading causes of infectious deaths in the world, claiming approximately 2 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, underscores 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). From 2004-2010, the MMRU served as the Wits/NHLS node of the DST/NRF Centre of Excellence for Biomedical TB Research (CBTBR). In January 2011, the MMRU moved to the University of Cape Town (UCT) and, in partnership with Wits and Stellenbosch Universities, now forms the UCT node of the CBTBR. The move to UCT coincided with the appointment of Professor Mizrahi as Director of the Institute of Infectious Disease and Molecular Medicine (IIDMM) at UCT. Professor Mizrahi has been an International Research Scholar of the HHMI since 2000 and currently serves on the Scientific Advisory Boards of the TB Alliance, K-RITH and SACEMA, as well as the Council of Scientific Advisors of the ICGEB and the Board of Directors of K-RITH.

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 biosynthesis and transportation of vitamin B12 and its role in mycobacterial metabolism; 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 metabolic vulnerability, drug resistance, persistence and tolerance.

The Unit comprises senior scientists, post-doctoral fellows, PhD and MSc students, and participates in several major TB drug discovery consortia funded by grants from the Bill & Melinda Gates Foundation under the TB Drug Accelerator program (IMTB and HIT-TB), the Seventh Framework Programme of the European Union (MM4TB), and the Technology Innovation Agency of South Africa (SATRII).