Ann Lab Med.  2018 May;38(3):189-195. 10.3343/alm.2018.38.3.189.

Characteristics and Immunological Roles of Surface Layer Proteins in Clostridium difficile

• Mori N
• Takahashi

• KMID: 2403451
• DOI: http://doi.org/10.3343/alm.2018.38.3.189

Abstract

Clostridium difficile is a major causative agent of antibiotic-associated diarrhea and has become the most common pathogen of healthcare-associated infection worldwide. The pathogenesis of C. difficile infection (CDI) is mediated by many factors such as colonization involving attachment to host intestinal epithelial cells, sporulation, germination, and toxin production. Bacterial cell surface components are crucial for the interaction between the bacterium and host cells. C. difficile has two distinct surface layer proteins (SLPs): a conserved high-molecular-weight SLP and a highly variable low-molecular-weight SLP. Recent studies have shown that C. difficile SLPs play roles not only in growth and survival, but also in adhesion to host epithelial cells and induction of cytokine production. Sequence typing of the variable region of the slpA gene, which encodes SLPs, is one of the methods currently used for typing C. difficile. SLPs have received much attention in recent years as vaccine candidates and new therapeutic agents in the treatment of C. difficile-associated diseases. Gaining mechanistic insights into the molecular functions of C. difficile SLPs will help advance our understanding of CDI pathogenesis and the development of vaccines and new therapeutic approaches. In this review, we summarize the characteristics and immunological roles of SLPs in C. difficile.

Keyword

Clostridium difficile; Surface layer proteins; Attachment; Innate immunity; Typing; Vaccine

MeSH Terms

Clostridium difficile*
Clostridium*
Colon
Diarrhea
Epithelial Cells
Germination
Immunity, Innate
Vaccines
Vaccines

Figure

• 

  Fig. 1 Amino acid sequence and schematic representation of the SlpA precursor protein. (A) Amino acid sequence of the SlpA precursor protein in Clostridium difficile 630 (GenBank: AJP12540.1). Amino acids highlighted in black indicate the signal peptide and those highlighted in gray denote residues involved in the interaction with the HMW-SLP. The amino acids comprising the LMW-SLP are underlined. The black triangle indicates the cleavage site that results in the generation of the two mature SLPs. (B) Schematic representation of the SlpA precursor protein. The black section represents the signal peptide, the light gray section denotes the conserved region within LMW-SLP, and the black triangle indicates the cleavage site of cysteine protease CWP84, which produces mature LMW-SLP and HMW-SLP.Abbreviations: SLPs, surface layer proteins; HMW, high molecular weight; LMW, low molecular weight; CWP84, cell wall protein 84.

• 

  Fig. 2 The SLPs of Clostridium difficile activate dendritic cells and macrophages, which in turn produce various cytokines and chemokines.Abbreviations: SLPs, surface layer proteins; TLR, toll-like receptor; IL, interleukin; IFN, interferon; MIP, macrophage inflammatory protein; MCP, monocyte chemotactic and activating factor; CD, cluster of differentiation; MHC, major histocompatibility complex; Th, T helper.

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