The characterization of secretion and cytolytic functionality of Mycobacterium virulence factors ESAT-6 and CFP-10

Abstract

Mycobacterium tuberculosis, the causative agent for the Tuberculosis disease, contains a genetic virulence locus named Region of Difference 1 (RD1). RD1 encodes for a novel secretion system that exports two small, immunogenic proteins named ESAT-6 and CFP-10. Although these proteins are involved in M.tuberculosis pathogenesis, their function remains largely unknown. This work employs the use of M.marinum, a species genetically closely related to M.tuberculosis, to study the homologous RD1 region with a focus on the function of ESAT-6 and CFP-10. This also involves the characterization of individual RD1 genes in the secretion and stability of ESAT-6 and CFP-10. The RD1 locus has been implicated in playing a role in bacterial spreading through host cell lysis and necrotic granuloma formation- a hallmark of pathogenic mycobacterium infections. Consequently, this study establishes the putative role of ESAT-6 and CFP-10 in pathogenesis via an investigation into their cytolytic abilities against host macrophages and the bacteria's subsequent ability to spread during infection.