The Type IX Secretion System and Its Role in Bacterial Function and Pathogenesis

Abstract

Porphyromonas, Tannerella, and Prevotella species found in severe periodontitis use the Type IX Secretion System (T9SS) to load their outer membrane surface with an array of virulence factors. These virulence factors are then released on outer membrane vesicles (OMVs), which penetrate the host to dysregulate the immune response to establish a positive feedback loop of chronic, inflammatory destruction of the tooth’s supporting tissues. In this review, we present the latest information on the molecular architecture of the T9SS and provide mechanistic insight into its role in secretion and attachment of cargo proteins to produce a virulence coat on cells and OMVs. The recent molecular structures of the T9SS motor comprising PorL and PorM as well as the secretion pore Sov, together with advances in the overall interactome, have provided insight into the possible mechanisms of secretion. We propose the presence of PorL/M motors arranged in a circle at the inner membrane with bent periplasmic rotors interacting with the PorN protein. At the outer membrane, we envisage a slide carousel model where the PorN protein is driven around a circular track composed of PorK. Cargo proteins are transported by PorN to PorW and the Sov translocon just as slides are rotated to the projection window. Secreted proteins are proposed to then be shuttled along highways consisting of the PorV shuttle protein to an array of attachment complexes distributed around the cell. The cell surface attachment of cargo is a hallmark of the T9SS, and in Porphyromonas gingivalis and Tannerella forsythia, this attachment is achieved via covalent bonding to a linking sugar synthesized by the Wbp/Vim pathway. The cell-surface attached cargo are enriched on OMVs, which are then released from the cell.

Interplay between the microalgae Micrasterias radians and its symbiont Dyadobacter sp. HH091

“…Highly active genes within this transcriptome belong to T9SS mechanism and gliding motility ( Supplementary Table S4 ). Overall, 18 genes ( gldA , gldB , gldD , gldF , gldG , gldH , gldI , gldJ , gldK , gldL , gldM , gldN , sprA , sprE , sprF , sprT , porU and porV ), required for gliding motility and protein secretion, and/or involved in T9SS ( Hunnicutt and Mcbride, 2000 ; McBride and Braun, 2004 ; Braun et al, 2005 ; Lauber et al, 2018 ; McBride, 2019 ; Hennell James et al, 2021 ; Trivedi et al 2022 ; Veith et al, 2022 ), were identified among DEGs ( Supplementary Table S2 ).…”

Type B CTD Proteins Secreted by the Type IX Secretion System Associate with PorP-like Proteins for Cell Surface Anchorage

“…It appears to localise in a helical manner, and it was proposed to be associated with the track on which SprB is propelled [ 37 , 38 ]. SprF may link SprB, directly or indirectly, to this track, which we recently proposed to also include the GldK and GldN proteins [ 39 ] ( Figure 7 B) that were pulled down at a slightly higher abundance than GldJ ( Figure 6 ).…”

A unique bacterial secretion machinery with multiple secretion centers

“…These finding have led to a model in which PMF-energy transduction regulates the activation states of the PorLM and GldLM translocation motors ( 14 , 25 ). Upon sensing of the PMF, PorLM and GldLM transduce PMF energy in the form of conformational changes in the periplasmic domains of PorM and GldM as a prerequisite for substrate secretion or gliding motility ( 25 , 26 ). In this context, we propose that the visualized conformational classes of the PorKMN complexes correspond to different activation states of the motors.…”