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

摘要

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 ESAT6 and CFP10. 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 ESAT6 and CFP10. This also involves the characterization of individual RD1 genes in the secretion and stability of ESAT6 and CFP10. The RD1 locus has been implicated in playing a role in bacterial spreading through host cell lysis and necrotic granuloma formationa hallmark of pathogenic mycobacterium infections. Consequently, this study establishes the putative role of ESAT6 and CFP10 in pathogenesis via an investigation into their cytolytic abilities against host macrophages and the bacteria's subsequent ability to spread during infection.