Intercellular communication via ESX-1 highlights essential role of ESX-4 in mycobacterial conjugation

Communal bacterial processes require intercellular communication mediated by secretion systems to coordinate appropriate molecular responses. Intercellular communication has not previously been described in mycobacteria. Here, we demonstrate new roles for two ESX secretion-system family members. We show that ESX-4, the enigmatic ESX family founder, is essential for conjugal recipient activity in Mycobacterium smegmatis. Remarkably, transcription of recipient esx4 genes requires both co-culture with a donor strain, and a functional recipient ESX-1 apparatus. Conversely, mutation of the donor ESX-1 apparatus amplifies the recipient esx4 transcriptional response. These reciprocal effects of ESX-1 on recipient esx4 transcription parallel conjugal DNA transfer efficiencies. Our data show that ESX-1 coordinates intercellular communication, controlling the expression of its evolutionary progenitor, ESX-4, culminating in conjugation between mycobacteria.