Title page for ETD etd-09212006-131351

Type of Document Master's Thesis
Author Therit, Blair H.
URN etd-09212006-131351
Title Investigation of the role of the toxins perfringolysin O (PFO) and sialidase in Clostridium perfringens gas gangrene infections
Degree Master of Science
Department Biological Sciences
Advisory Committee
Advisor Name Title
Melville, Stephen B. Committee Chair
Inzana, Thomas J. Committee Member
Sible, Jill C. Committee Member
  • perfringolysin O (PFO)
  • sialidase
  • gas gangrene
  • PMNs
  • listeriolysin O
  • diapedesis
  • monocytes
  • Clostridium perfringens
Date of Defense 2006-09-08
Availability unrestricted
Clostridium perfringens is the causative agent of gas gangrene. A lethal infection in mice requires a large inoculum suggesting that the immune system is involved in inhibiting disease. Human monocytic cells and neutrophils killed C. perfringens in vitro when complement was present. Macrophages and neutrophils co-localized with C. perfringens in vivo when bacterial numbers were low. Depletion of neutrophils and monocytes in mice revealed that monocytic cells play a role in inhibiting C. perfringens gas gangrene in mice infected with an intermediate dose.

C. perfringens can persist in the tissues and this could be mediated by persistence within macrophages. To examine if the toxin perfringolysin O (PFO) could mediate this, less active variants of PFO were used to examine what occurs between phagosomal escape and cell lysis. The mutant forms of PFO did mediate phagosomal escape in macrophages and were found within macrophages at higher numbers than wild-type C. perfringens. Our data were preliminary but may indicate that less active PFO mediates intracellular persistence.

To investigate the role of sialidase in C. perfringens gas gangrene we made nanI-, nanJ-, and nanI-/nanJ- mutants. We observed that NanI is responsible for the majority of sialidase activity of C. perfringens strain 13, that NanJ is an extracellular sialidase, and that these genes are transcriptionally regulated by sialic acid. Murine infection trials revealed that these sialidases may be protective for mice during infection.

In conclusion, murine monocytes inhibit disease onset and C. perfringens sialidase enhances mouse survival. However, the toxin PFO if less active promotes the survival of C. perfringens with macrophages.

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