The surface-layer protein of Clostridium tetani
Posted by ajcann on July 20, 2007
Clostridium tetani, a Gram-positive anaerobic bacterium, is best known as the causative agent of tetanus. The disease is characterized by a spastic paralysis mediated solely by tetanus toxin, a member of the family of clostridial neurotoxins. In a typical infection, spores enter a wound and following germination, the vegetative cells produce tetanus toxin, which is released from the bacteria and taken up at the neuromuscular junctions. Following this uptake, the toxin is transported to inhibitory interneurons in the spinal cord where it blocks exocytosis of inhibitory neurotransmitters. Despite the wide knowledge regarding the mechanism of action of the CNTs, little is known about the processes whereby C. tetani establishes a localized infection, enabling the production of tetanus toxin from the vegetative bacterium. Clostridium tetani infections are almost invariably found in anaerobic wounds, but in many cases the site of entry of the spores is minor and not found by the clinician. Nevertheless, the bacterium must interact with the host tissues and evade the immune response for a sufficient period to allow toxin production.
Many bacteria produce a surface layer, a paracrystalline array that completely surrounds the cell. Surface layers are usually composed of one or two surface-layer proteins (SLPs) or glycoproteins, which are expressed at very high levels on the surface of the bacterium. In some species, for example Camplyobacter fetus, the surface layer is a well-characterized virulence factor that undergoes antigenic variation. In Clostridium difficile, where the surface layer has been extensively characterized, it has been shown to act as an adhesin to host cells and to interfere with the immune response, disturbing the balance between inflammatory and regulatory cytokines. Based on the knowledge of the surface layer of C. difficile, an attractive hypothesis is that the surface layer of C. tetani may interact with host cells and/or the immune system to enhance the survival of the bacterium during and after toxin production.
Two proteins present in cell wall extracts from Clostridium tetani have been investigated and identified one of these has been unambiguously as the surface-layer protein (SLP). The gene, slpA, that encodes the SLP has been located in the genome of C. tetani. The molecular mass of the protein as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis is considerably larger than that predicted from the gene; however the protein does not appear to be glycosylated. Furthermore, analysis of five C. tetani strains, including three recent clinical isolates, shows considerable variation in the sizes of the SLP.
Identification and characterization of the surface-layer protein of Clostridium tetani
FEMS Microbiology Letters, July 2007
