Do Apx toxins of Actinobacillus pleuropneumoniae distract the immune response from recognizing the neutralizing determinants?

Abstract

Actinobacillus pleuropneumoniae (App) is the agent of contagious porcine pleuropneumonia: a widespread, severe and economically important respiratory disease of the pig.  Apx (pore-forming) cytolysins are crucial for virulence.  Protective immunity requires neutralizing antibody to the toxins, but vaccination with toxin fails to emulate this response.  This project will aim to understand why the neutralizing response is poor and find ways to improve the response.  Computational analysis will attempt to predict and understand toxin structure-function.  Peptides will be designed to generate neutralizing response while excluding distracting regions.  These will be tested by immunization of pigs and analysis of the cytolytic neutralizing response.




References:
[1]

Rycroft, A.N., Williams, D. Cullen, J.M. & Macdonald J. (1991).  The cytotoxin of Actinobacillus pleuropneumoniae (pleurotoxin) is distinct from the haemolysin and is associated with a 120 kDa polypeptide.  Journal of General Microbiology.  137, 561-568.  

[2]

Bossé, J.T., Janson, H, Sheehan, B.J. Beddek, A.J., Rycroft, A.N., Kroll, J.S. & Langford, P.R.  (2002).  Actinobacillus pleuropneumoniae: pathobiology and pathogenesis of infection.  Microbes and Infection 4, 225-235.

[3]

Cruijsen, T., van Leengoed, L.A., Kamp, E.M., Bartelse, A., Korevaar, A., Verheijden, J.H. (1995).  Susceptibility to Actinobacillus pleuropneumoniae infection in pigs from an endemically infected herd is related to the presence of toxin-neutralizing antibodies.  Vet Microbiol. 47, 219-228.

[4]

Seah, J.N. & Kwang, J.  (2004).  Localization of linear cytotoxic and pro-apoptotic epitopes in RTX toxin ApxIII of Actinobacillus pleuropneumoniae.  Vaccine 22, 1494-1497.

[5]

Lainson et al. (1996).  Characterization of epitopes involved in the neutralization of Pasteurella haemolytica serotype A1 leukotoxin. Microbiology 142 , 2499-2507.


Biological Areas:

Biotechnology
Microbiology

BBSRC Area:

Animal disease, health and welfare