Functional analysis of type VII secretion system links to host immune evasion mechanism in Mycobacterium tuberculosis

Mycobacterium tuberculosis causes tuberculosis, an infectious disease; this acid-fast bacillus has various functions that enable it to survive within the host. Importantly, the type VII secretion system plays a vital role in host immune evasion. However, the early secretory antigenic target secretion system (ESX) component is crucial for mycobacteria survival, plays a significant role in bypassing the host immune response, and is linked to the prognosis of the disease. The review aims to analyze the ESX-associated genes' functions in defence mechanisms against host immune response. There are five types of ESX, with the ESX-1 effectors consisting of the heterodimers EsxA/ESAT-6 and EsxB/CFP-10. The precise membranolytic role of EsxA remains unclear; however, mycobacterial mutants deficient in EsxA show reduced membrane lytic activity and lack the ability to perforate phagosomes. ESX-5 substrates, such as glycine-rich and repetitive PE_PGRS proteins, are associated with immune evasion and pathogenicity. ESX-5 releases a substantial amount of PE and PPE proteins, along with various other immune-modulating substrates. In addition, ESX-3 facilitates iron acquisition through mycobactin and regulates metal homeostasis. ESX 4 has been studied in two fast-growing mycobacterial species: M. abscessus and M. smegmatis. Notably, conjugal DNA transfer in the recipient strain of M. smegmatis requires ESX-4. Therefore, the type VII secretion system of ESX-associated genes plays a crucial role in bacterial survival and action against autophagosome-lysosome fusion. Thus, studying this system will explore the effects of specific antigenic structures and their relationships with autophagy and mycobacterial self-defense mechanisms.