The ESAT-6/CFP-10 secretion system of Mycobacterium marinum modulates phagosome maturation

The ESAT-6/CFP-10 secretion system is an important virulence determinant of Mycobacterium tuberculosis. However, the specific functions of the secretion system are currently unclear. Genes encoding the ESAT-6/CFP-10 secretion system is conserved in pathogenic Mycobacterium marinum, a close relative of M. tuberculosis. An M. marinum mutant with a non-functional ESAT-6/CFP-10 secretion system is characterized in this study. Results show that mutant bacteria were unable to replicate in J774 macrophages. Comparative analysis of phagosome maturation by assessing phagosome acquisition of late endosome/lysosome marker LAMP-1, phagosome acidification and phagolysosome fusion demonstrates that in contrast to wild type parental strain, a significantly higher percentage of the mutant bacteria resided in acidified, LAMP-1 positive phagosomes and are fused with lysosomes. These results suggest a novel function for the secretion system in modulating phagosome maturation and thereby promotion of intracellular survival. This finding provides a mechanism by which the ESAT-6/CFP-10 secretion system may potentiate the virulence of pathogenic mycobacteria.