Disconnecting in vitro ESX-1 secretion from mycobacterial virulence.

In this issue of the Journal of Bacteriology, Chen and colleagues (1) report a novel observation regarding the mycobacterial ESX-1 (ESAT-6 system-1/type VII) protein secretion system. Although the mechanisms underlying their observations are not yet understood, their exciting results unlink the in vitro secretion of the two major ESX-1 substrates, ESAT-6 (EsxA) and CFP-10 (EsxB), from M. tuberculosis virulence for the first time. These findings force us to reconsider how we relate the read-out of in vitro secretion assays to ESX-1 function within an infected host and call into question the roles of ESAT-6 and CFP-10 during infection.