The Ruler Protein EscP of the Enteropathogenic Escherichia coli Type III Secretion System Is Involved in Calcium Sensing and Secretion Hierarchy Regulation by Interacting with the Gatekeeper Protein SepL

Abstract

The type III secretion system (T3SS) is a multiprotein complex that plays a central role in the virulence of many Gram-negative bacterial pathogens. To ensure that effector proteins are efficiently translocated into the host cell, bacteria must be able to sense their contact with the host cell. In this study, we found that EscP, which was previously shown to function as the ruler protein of the enteropathogenic Escherichia coli T3SS, is also involved in the switch from the secretion of translocator proteins to the secretion of effector proteins. In addition, we demonstrated that EscP can interact with the gatekeeper protein SepL and that the EscP-SepL complex dissociates upon a calcium concentration drop. We suggest a model in which bacterial contact with the host cell is accompanied by a drop in the calcium concentration that causes SepL-EscP complex dissociation and triggers the secretion of effector proteins.

SsaV Interacts with SsaL to Control the Translocon-to-Effector Switch in the Salmonella SPI-2 Type Three Secretion System

“…The complete absence of SsaP also led to undetectable secretion of both SseB and SseJ, arguing against a significant contribution of these proteins in the translocon-to-effector switch. This is in contrast to the situation in other T3SSs, where EscP and specific cleavage of YscU are required for the switch from secretion of needle/inner rod proteins to translocon proteins (but not effectors) and where EscP is involved in the second switch ( 31 – 33 , 48 ).…”

The PopN gate-keeper complex acts on the ATPase PscN to regulate the T3SS secretion switch from early to middle substrates inPseudomonas aeruginosa

“…In the resting state before the beginning of the T3SS secretion process, we propose that the SctW complex is recruited to the T3SS sorting platform through binding to SctN and to SctU-SctP at the same time ( Figure 5A). Indeed, the ruler SctP was shown to directly interact with the gate-keeper SctW (Shaulov et al, 2017). This SctW-SctN interaction would allow needle complex recognition by enabling its interaction with the ATPase while SctU would prevent translocators and effectors to be loaded into the T3SS.…”

Tandem tyrosine residues in the EPEC multicargo chaperone CesT support differential type III effector translocation and early host colonization

“…Additional pathogenicity islands found within the EHEC and EPEC chromosomes encode effectors that are secreted by the LEE encoded T3SS (16–19). Interestingly, a temporal hierarchy for translocon protein secretion (EspA, B and D) and effector secretion has been observed (20–22), indicating that EPEC has a tiered mechanism to first coordinate translocon and subsequently effector injection into host cells. Low calcium sensing by EPEC has been implicated in transitioning from translocon to effector protein secretion (20).…”

“…Interestingly, a temporal hierarchy for translocon protein secretion (EspA, B and D) and effector secretion has been observed (20–22), indicating that EPEC has a tiered mechanism to first coordinate translocon and subsequently effector injection into host cells. Low calcium sensing by EPEC has been implicated in transitioning from translocon to effector protein secretion (20). The first secreted, or hierarchical effector, is the t ranslocated i ntimin r eceptor (Tir) (23, 24), although the mechanism behind this hierarchy remains elusive.…”