Grant: Project Grant

Mycobacteria, such as Mycobacterium tuberculosis, are the deadliest bacterial pathogens, responsible for over 1.5 million deaths annually. One of the major reasons for the success of these pathogens is their unique and highly impermeable cell envelope, consisting of two membranes. While this envelope serves as a crucial barrier for survival during infection by conferring resistance to numerous antibiotics, it must simultaneously permit nutrient uptake and protein secretion for vital interactions with the host. To overcome these challenges, Mycobacteria have evolved a unique secretion system, the type VII secretion system (T7SS), as their main machinery that allows them to transport substrates, while maintaining the integrity of their cell envelope. While some substrates are important for virulence, others are essential for the uptake of specific metabolites that support mycobacterial growth. Elucidating the mechanism of T7SS secretion and the role of individual effector proteins is therefore crucial for understanding the success of pathogenic mycobacteria. Outcomes from this work could facilitate the identification of novel targets for drug and vaccine development.