The mycobacterial ESX-3 secretion system is involved in host iron sequestering during Mycobacterium tuberculosis (M.tb) infections. Iron is one of the most important virulence factors of M.tb and ESX-3 is a prerequisite for mycobacterial growth. The proteins of ESX-3 might therefore constitute interesting drug targets or new vaccine antigens.
In here, protein interactions are indicated between three structural proteins of ESX-3. These proteins are suggested to form a membrane bound transporter complex that might be an efficient drug target to control bacterial growth.
Vaccines currently in clinical trials are based on immunodominant antigens that are strongly recognized during infection. This study demonstrates substantial protective efficacy of three uncharacterized proteins from ESX-3 that do not induce detectable immune responses in infected animals. One of these, confer higher protection levels than what is observed for other well-known vaccine antigens. Vaccination with this kind of subdominant antigens, allows priming of new protective antigens on top of a pre-existing immune response after exposure to M.tb.. Administering this antigen to latently infected individuals can therefore be speculated to prevent disease reactivation which states this antigens as a promising candidate for making up the backbone in a new generation of subunit vaccines against M.tb.