An actin‐stabilizing peptide conjugate deduced from the major outer sheath protein of the bacterium Treponema denticola

Abstract

A synthetic peptide conjugated to bovine serum albumin, P34(BSA), based on a 10-mer in the deduced amino acid sequence of the major outer sheath protein of Treponema denticola, was found to stabilize actin filaments of fibroblasts. Pretreatment of cells with P34(BSA) inhibited the actin disruption induced by cytochalasin D and latrunculin B. P34(BSA) was taken up by the cells and localized among actin filaments. P34(BSA) bound actin from fibroblast lysates, and cell exposure to P34(BSA) led to the activation of RhoA, a key regulator of actin filament assembly in fibroblasts. Exposure of fibroblasts to P34(BSA) retarded their migration on a collagen substratum. P34(BSA) also inhibited chemotaxis of murine neutrophils. Our findings with a novel peptide conjugate imply that bacterial proteins known to perturb the cytoskeleton represent a rich source of molecular models upon which to design synthetic reagents for modulating actin-dependent cellular functions.

Treponema denticola Msp‐deduced peptide conjugate, P34BSA, promotes RhoA‐dependent actin stress fiber formation independent of its internalization by fibroblasts

“…These findings prompted further studies of the cell-binding, translocation, and signalling of the P34 BSA conjugate. We reported previously that P34 BSA was internalized by fibroblasts but not by the same endocytic pathway as transferrin, that it bound and aggregated actin filaments in vitro, and that it activated RhoA, a key regulator of actin filament dynamics [Subauste et al, 2000;Amin et al, 2007]. Yet, the actual pathways and mechanisms that accounted for its profound effect on actin stress fibers were not investigated.…”

“…We have recently identified a bioactive peptide of Msp, which, when conjugated to BSA as P34 BSA , promotes actin stress fiber formation and actin filament stability in cells exposed to the actin inhibitors cytochalasin D and latrunculin B [Amin et al, 2007]. P34 BSA was unique in this regard among Msp-deduced synthetic peptide-BSA conjugates, and its activity depended on its lysine residues.…”

Neutrophil Role in Periodontal Disease

“…T. denticola major outer sheath protein (Msp) is one of its most important virulence factors in contributing to the disease progression. This membrane protein modulates neutrophil signaling pathways involved in cytoskeletal dynamics that are relevant in chemotaxis and phagocytosis [70]. Msp controls neutrophil cytoskeletal functions like migration, adhesion, and cell shape.…”

Tobacco-gene activity profile in Porphyromonas gingivalis, Filifactor alocis and Treponema denticola.

“…Tobacco-induced susceptibility to periodontitis was also believed to be associated (198,200,201), which was contradicted in a recent study which showed that smokers with periodontitis has decreased bacterial diversity (221).…”

“…It is also one of the immunodominant T. denticola antigens recognized by human serum antibodies (196). Msp interaction leads to actin remodeling and reorganization in host cells, which is likely how it impairs neutrophil chemotaxis and phagocytic activity (197)(198)(199)(200).…”