Tuberculosis has probably killed more humans than any other disease in history, and on average four people die of this disease every minute around the world (1). The causative agent, Mycobacterium tuberculosis, is a Gram-positive bacterium that can lie dormant in the body for decades before reawakening to cause acute disease. One of the major ways that bacteria subvert host defenses is by secreting virulence proteins. Indeed, pathogenic bacteria have evolved a number of elaborate transport machines whose sole function is to deliver such factors into the host, often carefully timed to hit the right place at the right time. Recently, a new protein secretion pathway, ESX-1 (ESAT-6 system-1) or Snm (secretion in mycobacteria), was discovered in M. tuberculosis (2-5), and is present in many other Gram-positive bacteria (6). This discovery has challenged our knowledge of the organism and more generally of protein secretion in prokaryotes. On page 1632 of this issue, DiGiuseppe Champion et al. (7) identify the first targeting signal that promotes protein secretion by this pathway.
展开▼
