Induction of De Novo Subcortical Actin Filament Assembly by Treponema denticola Major Outer Sheath Protein

Abstract

Treponema denticola and its major outer sheath protein (Msp) induce actin reorganization in fibroblasts. We adapted a barbed-end labeling/imaging assay to monitor Msp-induced subcortical actin filament assembly in neutrophils and fibroblasts. Msp, at an actin-reorganizing concentration, inhibited migration of these dissimilar cell types, whose cytoskeletal functions in locomotion and phagocytosis are crucial for immunity and healing of peripheral infections.

Modulation of Human Neutrophil Functions In Vitro by Treponema denticola Major Outer Sheath Protein

“…These key outcomes impacting the cytoskeleton help explain how Msp may inhibit PMN chemotaxis, perhaps through its impact on cytokinesis. The findings are consistent with previous reports that Msp pretreatment of fibroblasts leads to actin reorganization, diminished calcium store release, and delayed migration (1,27).…”

“…1B), indicating that Msp rather than a minor protein or heat-stable contaminant, such as a glycolipid, was the predominant bioactive ingredient. These findings with human PMNs extend a previous observation that Msp (20 g/ml) impaired chemotaxis of murine PMNs in a Zigmond chamber, in which PMNs migrate laterally from central coordinates on a slide (1).…”

“…Yet there is little knowledge of the T. denticola factors that may modulate key antimicrobial pathways and mechanisms in PMNs. The crucial role of the cytoskeleton in migration and endocytosis, combined with previous findings that the major outer sheath protein (Msp) of T. denticola perturbed actin assembly in fibroblasts (1,15,27), suggested that Msp may modulate human neutrophil chemotaxis and phagocytosis.…”

Composition and Localization of Treponema denticola Outer Membrane Complexes

“…Msp, one of the most highly expressed T. denticola proteins, is a pore-forming outer membrane protein that has lytic effects on erythrocytes and epithelial cells (20) and disrupts regulation of both actin (2,46) and intracellular calcium (2,47) in fibroblasts. Like other members of the porin family, native Msp is a detergent-stable trimeric complex.…”

Mutagenesis of a Novel Gene in the prcA-prtP Protease Locus Affects Expression of Treponema denticola Membrane Complexes

“…Both Msp and PrcA-PrtP exhibit adhesin-like binding activity and are cytotoxic to epithelial cells (7). Recent reports implicate Msp in the disruption of fibroblast calcium responses and cytoskeletal assembly (1,3). PrtP activity contributes to T. denticola tissue penetration (4,12) and modulation of inflammatory cytokine responses (2,5).…”