Bacterial type III secretion systems: a complex device for the delivery of bacterial effector proteins into eukaryotic host cells

Abstract

Virulence-associated type III secretion systems (T3SS) serve the injection of bacterial effector proteins into eukaryotic host cells. They are able to secrete a great diversity of substrate proteins in order to modulate host cell function, and have evolved to sense host cell contact and to inject their substrates through a translocon pore in the host cell membrane. T3SS substrates contain an N-terminal signal sequence and often a chaperone-binding domain for cognate T3SS chaperones. These signals guide the substrates to the machine where substrates are unfolded and handed over to the secretion channel formed by the transmembrane domains of the export apparatus components and by the needle filament. Secretion itself is driven by the proton motive force across the bacterial inner membrane. The needle filament measures 20–150 nm in length and is crowned by a needle tip that mediates host-cell sensing. Secretion through T3SS is a highly regulated process with early, intermediate and late substrates. A strict secretion hierarchy is required to build an injectisome capable of reaching, sensing and penetrating the host cell membrane, before host cell-acting effector proteins are deployed. Here, we review the recent progress on elucidating the assembly, structure and function of T3SS injectisomes.

Advances on Vibrio parahaemolyticus research in the postgenomic era

“…The gatekeeper protein SctW is involved in the switching from middle to late substrates . The gatekeeper interacts with the export‐apparatus protein SctV, which may favor the secretion of translocators, but not of effectors . In V. parahaemolyticus , two gatekeeper proteins have been identified: the V. parahaemolyticus gatekeeper protein A (VgpA) and VgpB, which are encoded in the Vp‐PAI (Figure ).…”

“…The switching from middle to late substrates is triggered upon contact with host cells . T3SSs presumably sense host cell contact, which induces the release of the gatekeeper from the export apparatus, resulting in the secretion of effectors . Several chemical conditions, including calcium ions, potential of hydrogen (pH), and Congo red, are signals for the sensing of host cells by T3SSs .…”

“…50,51 The gatekeeper interacts with the export-apparatus protein SctV, which may favor the secretion of translocators, but not of effectors. 59,60 In V. parahaemolyticus, two gatekeeper proteins have been identified: the V. parahaemolyticus gatekeeper protein A (VgpA) and VgpB, which are encoded in the Vp-PAI 61 (Figure 1). The absence of VgpA or VgpB causes diminished secretion of the VopB2, VopD2, and VopW translocators and hypersecretion of T3SS2 effectors, a feature that is consistent with that of the gatekeeper.…”

“…49,51 T3SSs presumably sense host cell contact, which induces the release of the gatekeeper from the export apparatus, resulting in the secretion of effectors. 60 Several chemical conditions, including calcium ions, potential of hydrogen (pH), and Congo red, are signals for the sensing of host cells by T3SSs. [62][63][64] However, these conditions do not switch the secretion of T3SS2 from V. parahaemolyticus.…”

LITESEC-T3SS - Light-controlled protein delivery into eukaryotic cells with high spatial and temporal resolution

“…The injectisome is a bacterial nanomachine capable of translocating proteins into eukaryotic host cells in a one-step export mechanism 1 , 2 . The core components of the injectisome, or type III secretion system (T3SS) § are shared with the bacterial flagellum 3 , 4 .…”