Abstract
Tuberculosisis the second leading cause of death worldwide. The researchers still finding way to eradicate TB. There is an urgent need to discover new drug which is more effective and less toxic to combat drug resistance. This article reports potential of ES-31 antigen as a new drug target. The characterization of ES-31 antigen showed that ES-31 is a 31 kDa protein antigen and has serine protease as well as lipase activities and shown to be a chymotrypsin-like protein which is having catalytic triad responsible for both activities. Addition of serine protease inhibitors (53-76%), metallo protease inhibitor (46-61%), lipase inhibitor (61%) or anti-ES-31 serine protease antibody (89%) strongly inhibited the MTB H37Ra growth in axenic culture. The importance of excretory secretory ES-31 antigen for the survival of MTB H37Ra and H37Rv bacilli has been shown by 77% and 78% growth inhibition in macrophage culture by protease inhibitor pefabloc. Inhibition of ES-31 leads to growth inhibition of MTB bacilli, suggests that it may be an important drug target for exploring new drugs for tuberculosis.
Highlights
Tuberculosis (TB) has been the major cause of morbidity and mortality throughout the world
As it was hypothesized that chymotrypsin-like proteases possess both serine protease as well as lipase activity with the specific catalytic triad present in the active site of the enzyme [15,16,17]
The lipase activity of Excretory Secretory-31 (ES-31) was 100% inhibited by serine protease and metallo protease inhibitors (PMSF (1 mM) and Ethylene diamine tetracetic acid (EDTA) (1 mM)) as well as lipase inhibitor (Orlistat)
Summary
Tuberculosis (TB) has been the major cause of morbidity and mortality throughout the world. Development of new anti-TB drugs with good therapeutic or prophylactic potential has not been progressed, though there is urgent need to prevent mortality and morbidity related to tuberculosis. The most popular group of secreted proteins of Mycobacterium tuberculosis is Ag 85 complex The role of these proteins is being illustrated as essential aspect of immune response after infection, development of protective immunity and in complications of the disease [4]. For more than two decades, our laboratory has been actively involved in immune screeing of both pulomonary and extra pulmonary tuberculosis using various ES proteins. ES-31 protein showed serine protease and lipase activities with good drug target potential [10,11]. Control Pefablocb 3,4 dichloroisocoumarinb Phenyl methyl sulfonyl fluoride (PMSF) b Ethylene diamine tetracetic acid (EDTA) c 1,10 phenanthroline c Isoniazid Anti-ES-31 serine protease antibody
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