Research Projects

Bacteriophages or phages are the most numerous biological entities in the biosphere, with an estimated 1031 particles. They code numerous protein factors capable of modulating host machinery for their growth advantages. Hence they are one of the richest resources for novel biological macromolecules. The emergence of multidrug-resistant bacteria has led investigators to revisit the utilities of the phages and phage-coded proteins as alternative therapeutics. These phage proteins could be used to validate bacterial drug targets as well as they could be used as platforms for designing peptides with bactericidal properties. Mycobacteriophages infect slow and fast-growing mycobacterial hosts, such as Mycobacterium tuberculosis and Mycobacterium smegmatis. To date, thousands of mycobacteriophages have been isolated using a single host strain, M. smegmatis mc2155 and the genome of a large number (over 2200) of those have been completely sequenced. Mycobacteriophages display remarkable genetic diversity. Most of these families do not have homologs outside of the mycobacteriophages and most genes are of unknown function. Interestingly, functions of ~ 70% of the gene products (gp) of these sequenced phages could not be predicted because they are not significantly similar to any other proteins with known functions. Therefore, it would be worth investigating novel mycobacteriophage proteins having bactericidal properties. This project focuses on the screening and structure-function characterization of mycobacteriophage-encoded molecules that are bactericidal. Characterization of these regulatory phage-proteins will lead to the development of therapeutic peptides against M. tb as well as other bacterial pathogens.