Team:Tongji China/T3SS

T3SS

Background

Type III secretion system
(T3SS)

Type III secretion system (T3SS) is a highly coordinated multi-protein system which consists of structural, regulatory and secreted proteins. The structure of the type III secretion nanomachine is highly conserved among Gram-negative bacteria, and we defined it as "injectisome". Due to making good use of its infecting potential, T3SS can be an amazing tool to deliver proteins. The moment we found this surprising tool in literature, we decided to utilize this system to deliver our item antigens.

Structure - injectisome

In fact, the structure of T3SS looks quite like a needle tubing, and its function is like a needle tubing as well. That is why we called it "injectisome". The T3SS injectisome is composed of a needle complex, an inner membrane export apparatus, and a cytoplasmic platform that energizes the secretion process and selectively sorts substrates for their orderly delivery to the secretion machine.

The needle complex is composed of a multi-ring cylindrical base with ~26 nm in diameter that is anchored on the bacterial envelope and a needle-like structure that projects ~60 nm from the bacterial surface. The entire structure is traversed by a channel ~2 nm in diameter that serves as a conduit for the passage of proteins injected through the type III secretion machinery. An ATPase at the cytoplasmic sorting platform provides energy for the protein export.

Figure1 (left). Injectisome structure

Figure2 (right). Delivery process

Process - delivery

The bacterial T3SS has been exploited to deliver antigenic peptides and proteins into various target cells. Type III effectors were shown efficiently injected into a wide range of host cells, including professional antigen presenting cells (APC), such as macrophages and dendritic cells (DCs) .

First T3SS comes into being by attaching with host cells, the attachment triggers the formation of the translocon. A set of pore-forming proteins are transported through the needle and are inserted into the eukaryotic cell membrane to form the translocon. Following the pore formation, type III secretion regulatory protein (repressor) is secreted, resulting in transcriptional activation of the whole T3SS regulon genes.

Then our antigens can be translated into protein and delivered by the bacterial T3SS with the aim to elicit immune response (vaccination) or cancer immunotherapy. They go through the needle complex and pass the translocon, and finally enter the host cell cytosol. This means that our item antigens is successfully injected into the host cell without wasting them into the culture supernatant nor the formation of the vesicle.

References:
[1] Bai F, Li Z, Umezawa A et al. Bacterial type III secretion system as a protein delivery tool for a broad range of biomedical applications. Biotechnol Adv 2018;36:482–93.
[2] Galle M, Carpentier I, Beyaert R. Structure and function of the Type III secretion system of Pseudomonas aeruginosa. Curr Protein Pept Sci. 2012;13:831–42. doi: 10.2174/138920312804871210.

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