Contributor: Dr Bavesh Kana
He completed his PhD degree and postdoctoral fellowship at the MRC/NHLS/Wits Molecular Mycobacteriology Research Unit-DST/NRF Centre of Excellence for Biomedical TB Research. He has been the recipient of a Columbia University – Southern African Fogarty AIDS Training and Research Program fellowship, twice, for postdoctoral training in 2004/5 at the Public Health Research Institute (PHRI) in New Jersey and has also undertaken several short-term working visits to collaborating labs at the University of Pennsylvania (Pennsylvania), Texas A&M University (Texas) and Harvard Medical School (Massachusetts) in the USA.
Bavesh has also worked at CSIR during his doctoral studies. He has recently received the prestigious MRC Career Development Award and currently holds grants from the MRC, Wits and NHLS.
A major thrust of his current research is the study of the relationship between the occurrence of clinically latent tuberculosis infection and the microbiological phenomenon of bacterial dormancy which is usually characterized by impaired culturability. The ability of Mycobacterium tuberculosis to enter into a state of reduced metabolic activity, which renders it refractory to treatment by conventional antibiotics and promotes immune subversion, is critical to the success of this pathogen.
The resuscitation promoting factor (Rpf) is a muralytic enzyme that is predicted to cleave the 1,4 – ? – glycosidic bond in peptidoglycan and through an unknown mechanism significantly enhances the culturability of dormant Micrococcus luteus and aged mycobacterial cultures. Furthermore, the synergistic action of Rpfs with other peptidoglycan endopeptidases in M. tuberculosis may produce a range of molecules that play an important role in host immune and bacterial signalling, the latter involving the sensing of peptidoglycan by eukaryotic-like serine threonine protein kinases.
Bavesh has been involved in studying the five Rpf homologues in M. tuberculosis and their roles in peptidoglycan remodelling, growth, pathogenesis and recrudescence during infection with the hypothesis that Rpf may provide a novel way of modulating bacterial growth during infection and as such these factors represent an interesting unexplored area of anti-tubercular drug discovery.
He is also involved in the study of specialized DNA polymerases in M. tuberculosis and their role in genome plasticity and mutation which is pivotal to the evolution of drug resistance. In bacteria, low fidelity DNA polymerases (sloppy copiers) play a central role in promoting mutagenesis during DNA repair or whilst replicating across damaged DNA. In this regard, the Y-family of specialized polymerases has been shown to be important for mutagenesis in other organisms. M. tuberculosis possesses two umuC-like genes belonging to this family – dinB1 and dinB2 – whereas Mycobacterium smegmatis, a closely related saprophyte, possesses three. Whilst the role of a C-family polymerase in mutagenesis has been confirmed in mycobacteria, the function of the umuC-like genes is presently unknown.
His other active area of interest is the study of the mycobacterial electron transport chain, specifically the role of hypoxic and anaerobic respiratory complexes in energy metabolism under stressful conditions and during non-replicating persistence. The modular electron transport chain allows for bacterial growth and adaptation under varying environmental conditions and thus represents a potential point of metabolic vulnerability in M. tuberculosis as evidenced by the recent development of inhibitors that target several steps in this pathway.
Dr Bavesh Kana, Tel: +27 11 489 9030