Pathophysiological investigations of pneumonic pasteurellosis due to Pasteurella multocida type A:3 in calves

Dowling, Aileen Aisha (2003) Pathophysiological investigations of pneumonic pasteurellosis due to Pasteurella multocida type A:3 in calves. PhD thesis, University of Glasgow.

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Abstract

Pneumonia in young ruminants, caused by the Gram-negative bacterium Pasteurella multocida, world-wide is an infectious respiratory disease of major economic and welfare importance. P. multocida infection is on the increase, for unknown reasons, as the serotype A:3 that causes the majority of pneumonic disease has not been fully characterised. Greater knowledge of P. multocida A:3 may reveal the underlying mechanisms of pathogenesis that have not yet been elucidated. The aim of the work presented in this thesis was to expand knowledge of P. multocida, specifically with respect to serotype A:3. There are several published attempts to develop a suitable animal model of P. multocida infection but prior to this investigation none were reliable, reproducible or closely mimicked the field disease. As a consequence, progress towards a vaccine has been slow and there is currently no vaccine available to protect against disease caused by P. multocida A:3. In these studies the lipopolysaccharide (LPS) from P. multocida A:3, a potentially important virulence factor, was characterised and found to be of the rough form, indicating loss of the O- antigen responsible for variation in the bacterial isolates. This discovery may facilitate the development of vaccines targeted against LPS. Pulsed-field gel electrophoresis of DNA cut by enzymes with infrequently predicted restriction sites revealed the potential for much genetic diversity. An experimental model of pneumonic pasteurellosis caused by P. multocida A;3 was established to help determine mechanisms of pathogenesis. In this model, 300 ml of PBS containing 109 cfu of P. multocida produced progressive clinical and pathological responses comparable to those observed in field cases providing for the first time a model suitable for future experimental studies (Dowling et al., 2002). Furthermore haptoglobin and serum amyloid-A were found to be useful markers for the disease. Subsequent work confirmed the reliability and reproducibility of the model in terms of the clinical and pathological responses. Host-pathogen interactions at various stages of disease were assessed by 2-dimensional electrophoresis of bronchoalveolar lavage fluid isolated from calves infected with live P. multocida A:3 which revealed changes in antimicrobial peptides, annexins, antioxidant protein and apolipoprotein-1 precursor. Host responses to both live and killed P. multocida A:3 challenge were compared. Calves received either formalin killed P. multocida or saline, followed, at day 21, by challenge with live P. multocida. There were marked changes in both clinical scores and acute phase protein concentrations in responses to both treatments, with the highest values associated with formalin- killed P. multocida. Calves given formalin-killed P. multocida appeared to cope well with the bacterin challenge indicating a possible method for generating protection against exposure to a homologous challenge. The responses in calves given homologous live challenge after exposure to the bacterin were more severe than those calves given only the homologous challenge, suggesting that the bacterin compromised the animals' defences rather than enhancing protection. The in vitro interaction of macrophages with P. multocida was shown to be independent of opsonisation and the pathogen could survive in these cells for up to 1 hour, possibly by disabling the bactericidal function of the macrophage which may be significant to pathogenesis in the host. The work reported in this thesis led to a successful, progressive and reproducible animal model that has provided a detailed picture of the clinical and pathological responses following P. multocida infection. This study has provided a better understanding of the disease process and the host interaction with P. multocida A: 3 and from these novel findings more informed approaches to vaccine development should be possible.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Advisers: J C Hodgson; P D Eckersall
Keywords: Animal diseases
Date of Award: 2003
Depositing User: Enlighten Team
Unique ID: glathesis:2003-71029
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 09 May 2019 14:28
Last Modified: 09 May 2019 14:28
URI: http://theses.gla.ac.uk/id/eprint/71029

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