Pasteurella multocida causes major welfare problems and economic losses in a range of hosts and in many areas of the world. It is responsible for both respiratory and systemic disease in cattle and buffalo, but a detailed understanding of, and the ability to control, the underlying molecular mechanisms during host-pathogen interaction is lacking.
Acute bovine respiratory disease (ABRD) is a significant economic and welfare problem in calves despite widespread use of vaccines for several of the pathogens involved. Combined annual losses in the UK cattle industry from bacterial and viral respiratory disease are estimated at over £80 million with P. multocida re-emerging as a primary contributor, accounting for about 50% of pneumonic pasteurellosis in the UK. A recent Moredun survey of 68 dairy and beef farms throughout Scotland, involving 616 calves that appeared healthy, showed an overall prevalence for carriage of P. multocida in the upper respiratory tract of 17%, and that 47% of farms were affected. A higher prevalence was detected in dairy calves (26%) than in beef calves (9%).
There is no current test that differentiates between dangerous and less harmful forms of the bacterium, nor any European vaccine and the industry needs new and effective control measures. The disease haemorrhagic septicaemia, a form of endotoxin shock caused by P. multocida serotypes B and E, is of great socio-economic importance across South and Southeast Asia and sub-Saharan Africa. It affects all principal livestock species including cattle, water buffalo and camels, in which morbidity and mortality rates are high. Resultant losses of meat, milk and draught animals have devastating effects on the health and wealth of local communities where annual costs of several million US dollars are probable underestimates due to a lack of comprehensive surveillance data.
Vaccines are of short duration and unpopular because of adverse reactions and a new, effective and long-lasting alternative is needed urgently. The recent award from the Wellcome Trust Translational Fund of over £1M for 3 years will help produce and test a novel vaccine from a prototype developed in collaboration with colleagues at Glasgow University.
The current focus areas of the Pasteurella Research Group at Moredun are the molecular characterisation of bovine isolates of P. multocida during carriage and disease, what happens during infection and the involvement of biofilms in disease. The aim is to develop new diagnostic and control methods for diseases caused by this bacterium.
A recent molecular and clinical study in a mixed group of 40 initially healthy calves aged from 3 days to 3 weeks from 18 farms assessed disease transmission and development caused by P. multocida. A proportion of these calves were asymptomatic carriers of P. multocida and molecular characterisation of isolates obtained from nasal swabs showed close similarities in 7 carrier calves from 3 farms but a different pattern in 2 carrier calves from a fourth farm. Subsequent results showed that these 2 types of isolates differed in their ability to spread to and infect naïve calves – the common isolate from 3 farms infected 19 naïve calves whereas the isolate from farm 4 infected only 1 further animal. The resultant disease was multifactorial, with many samples positive also for M. haemolytica, Mycoplasma and bovine respiratory syncytial virus.
Culture of nasal secretions from calves developing ABRD indicate that each gram may contain 1010(or 10 billion) P. multocida, suggesting that exchange of nasal secretions between infected and naïve calves either directly or as an aerosol could be a major route of transmission. Our studies show that P. multocida is susceptible to most antibiotics in vitro but that systemic treatment with antibiotics is not a reliable method to clear nasal colonisation. This suggests that biofilm formation protects against the antibiotics. A biofilm is a community of microorganisms that can attach to biological surfaces encapsulated in a selfsynthesised polysaccharide matrix. Whereas antibiotics work best against rapidly-dividing bacterial cells, biofilms are slow-growing and the extraordinary resistance to antimicrobials may be due to ‘persister cells’ that neither grow nor die in the presence of bactericidal agents but protect against immune cells or drugs and repopulate the biofilm after treatment. Work in vitro has shown that P. multocida is able to form biofilms, and this may help explain its resistance to clearance in vivo. Our work is continuing to try and understand more about these processes so that we can control diseases caused by this bacterium more effectively in the future.
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