Treponema denticola, a bacterium that forms a "red complex" with Porphyromonas gingivalis and Tannerella forsythia, is associated with periodontitis, pulpitis, and other oral infections. The major surface protein (Msp) is a surface glycoprotein with a relatively well-established overall domain structure (N-terminal, central and C-terminal regions) and a controversial tertiary structure. As one of the key virulence factors of T. denticola, Msp is associated with adherence, immune response, and pore formation by the microorganism. It also mediates several pathological changes in histocytes, such as cytoskeleton disruption, neutrophil phagocytosis, and phosphoinositide balance interruption. In addition, the Msp of T. denticola is also an ortholog of the Treponema pallidum repeat (Tpr) proteins and Msp or Msp-like proteins that have been detected in other oral treponeme species. This review will discuss the structure, pathogenicity and homologs of Msp produced by T. denticola, illuminate the controversy regarding the structure and membrane topology of native Msp, explore the potential roles of Msp in the mechanism of T. denticola immune escape and provide an overview of the cytotoxicity and adherence ability of Msp. Further understanding of the structure and functions of Msp will offer new insights that will help promote further investigations of the pathogenic mechanisms of T. denticola and other treponemes, leading to more effective prophylactic or therapeutic treatments for relevant diseases.
Keywords: T. pallidum repeat (Tpr) family; Treponema denticola; Major surface protein (Msp); Oral Treponema.
© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.