Transmembrane substrates of type three secretion system injectisomes

Abstract

The type three secretion system injectisome of Gram-negative bacterial pathogens injects virulence proteins, called effectors, into host cells. Effectors of mammalian pathogens carry out a range of functions enabling bacterial invasion, replication, immune suppression and transmission. The injectisome secretes two translocon proteins that insert into host cell membranes to form a translocon pore, through which effectors are delivered. A subset of effectors also integrate into infected cell membranes, enabling a unique range of biochemical functions. Both translocon proteins and transmembrane effectors avoid cytoplasmic aggregation and integration into the bacterial inner membrane. Translocated transmembrane effectors locate and integrate into the appropriate host membrane. In this review, we focus on transmembrane translocon proteins and effectors of bacterial pathogens of mammals. We discuss what is known about the mechanisms underlying their membrane integration, as well as the functions conferred by the position of injectisome effectors within membranes.

The sequence of events of enteropathogenic E. coli’s type III secretion system translocon assembly

“…These regions include the highest level of sequence identity among the translocon proteins. 48 We have previously shown that replacement of these TMDs, even by TMDs from other TMD-containing secreted proteins, impairs post-secretion function of these translocon components and prevents the formation of functional pores. 35 Here, we considered whether the EspB TMD-exchanged variants were defective in terms of their ability to dimerize and integrate into EspD oligomers.…”

Pathogenicity and virulence of Yersinia

“…In addition to their role in the translocation of Yops, YopD and LcrV may have additional roles in modifying the host response to infection as both YopD and LcrV have been found to localize to the host cell cytoplasm [ 127 , 128 ]. Furthermore, functional homologs of YopB, YopD, and LcrV are found in most T3SSs expressed by gram-negative bacteria, where strong evidence supports their direct roles on the host cell response [ 129 ]. Insertion of the translocation pore into host membranes connects the cytoplasm of the two cells, allowing direct injection of effector Yops into the host cytoplasm.…”