Host Resistance to Avian Pathogenic E. coli

Avian colibacillosis is a severe and recalcitrant disease that constrains the health, welfare and productivity of poultry worldwide. It is the most common infectious disease affecting turkeys, layers, and broilers. Infections are frequently initiated by inhalation of faecal dust containing avian pathogenic Escherichia coli (APEC) and are often secondary to respiratory viral or Mycoplasma infections. Immaturity of the immune system in neonates and suppression of immune function at the onset of sexual maturity or under stress are also key risk factors, though how such factors act at the respiratory mucosa is ill-defined. Respiratory distress is common following APEC infection and the bacteria often translocate to the blood and internal organs, causing a variety of problems, including sepsis, hepatitis, and cellulitis. Losses are incurred via increased mortality, reduced productivity, condemnation of carcasses at slaughter, and decreased egg yield and egg quality in layers. The scale of the problem is vast. In the United Kingdom, a recent survey of 4 broiler flocks sampled weekly for 4 weeks found evidence of colibacillosis in 39% of dead birds. A separate analysis of causes of death 2-3 days after placement of broiler chicks found evidence of colibacillosis in 70% of dead birds. Although the incidence of the disease varies with geographical location, species and production system, a common feature is the high diversity of APEC associated with the bacterial isolates from diseased birds. E. coli diseases result in annual multimillion pound losses by the worldwide poultry industry.

Our goal in this project is to define the genetic and immunological basis of avian resistance to respiratory Escherichia coli infection so as to inform the design of vaccines and genomic selection strategies. In our integrated and synergistic project, we will exploit unique inbred chicken lines in both countries that differ in resistance to APEC, analyze transgenic chickens in which all cells of the myeloid lineage express a fluorescent protein to aid sorting and phenotyping of APEC-infected cells, use state-of-the-art methods to define the transcriptome of infected cells and associate resistance with bird genotype, and validate selected research findings for translation into industry application. An urgent need exists to improve control of this key endemic avian disease, yet there is a striking paucity of research on avian airway responses to APEC and the basis of heritable host resistance. Our genomic, molecular and cellular characterization of the host-pathogen interactions between chickens and APEC will identify critical control points that can be used to enhance resistance to APEC through veterinary and breeding strategies. Our long-term goal is to reduce the occurrence and negative impact of this disease on the poultry industry through development of control strategies that are based on a thorough understanding of the host's functional responses to E. coli infection.

Avian colibacillosis is a severe and recalcitrant disease that constrains the health, welfare and productivity of poultry worldwide. It is the most common infectious disease affecting turkeys, layers, and broilers. Losses are incurred via increased mortality, reduced productivity, condemnation of carcasses at slaughter, and decreased egg yield and egg quality in layers. The scale of the problem is vast. In the United Kingdom, a recent longitudinal survey of 4 broiler flocks sampled weekly for 4 weeks found evidence of colibacillosis in 39% of dead birds. A separate analysis of causes of mortality 2-3 days after placement of broiler chicks found evidence of colibacillosis in 70% of dead birds. Though incidence varies with geographical location, species and production system, a common feature of such surveys is the high diversity of APEC associated with the bacterial isolates from diseased birds. E. coli diseases result in annual multimillion dollar losses by the US poultry industry due to morbidity, mortality, and condemnation of infected products.

Our goal in this project is to define the genetic and immunological basis of avian resistance to respiratory Escherichia coli infection so as to inform the design of vaccines and genomic selection strategies. In our integrated and synergistic project, we will exploit unique inbred chicken lines in both countries that differ in resistance to avian pathogenic E. coli (APEC), analyze transgenic chickens in which all cells of the myeloid lineage express a fluorescent protein to aid sorting and phenotyping of APEC-infected cells, use state-of-the-art methods to define the transcriptome of infected cells and associate resistance with bird genotype, and validate selected research findings to translate into industrial applications.

The work proposed has direct relevance to the BBSRC key strategic priority area of "Food Security" and in particular "Animal Health" and "Livestock Production". Outputs will include the identification of regions of the chicken genome associated with resistance/susceptibility to infection by one or more species of avian pathogenic E. coli (APEC), supplemented by characterisation of specific immune mechanisms underlying these traits to yield a panel of informative biomarkers. Outcomes will assist in increasing UK competitiveness in the global animal production market, improving animal welfare and helping to guarantee a secure supply of safe, healthy food. The following stakeholders have been identified as beneficiaries of this work:

1. The UK poultry production industry
Avian colibacillosis is a severe and recalcitrant disease that constrains the welfare and productivity of poultry worldwide. Losses are incurred via increased mortality, reduced productivity, condemnation of carcasses at slaughter, and decreased egg yield and quality in layers. The scale of the problem is vast. Identification of genomic regions associated with resistance to APEC infection will facilitate selection for inherently resistant poultry with no loss of productivity. The structure of the UK poultry industry is such that collaboration with the major breeding companies will provide a cascade of breeding developments, 'ensuring exchange of knowledge between the science base and industry through effective networking'.

2. The UK poultry breeding industry
Mapping quantitative trait loci associated with resistance to APEC infection and immune responses correlated with relevant immuno-competence will provide a panel of genetic and phenotypic biomarkers which may be developed as accurate, affordable tools to estimate disease susceptibility and inform breeding strategies.

3. Animal welfare
The effective reduction of disease as a result of improved breeding supports the Five Freedoms implicit to animal welfare as set out by the Farm Animal Welfare Council.

4. General public and the environment
Increased efficiency in poultry production will raise poultry product availability at a lower cost for the consumer, contributing to improved food security. Consequences of improved disease resistance include a reduction in the requirement for prophylactic chemotherapy, reducing drug consumption and the risk of contamination to the food chain and the environment. The world's chicken flock is now estimated to be around 21 billion, producing 1.1 trillion eggs and 60 billion broilers every year. Alleviating the burden of mortality and morbidity due to E. coli in poultry could therefore have a significant impact on economic and societal prosperity.

5. Skills, knowledge and training
The multidisciplinary nature of this project will provide opportunities for broad training to all staff, in addition to other members and students of each host institution.

6. International development
APEC impose serious costs on animal production in developing counties. Translating 'high quality, innovative, strategic research within UK universities and institutes to improve the resistance of farmed animals to pest and disease organisms' can improve economic income and alleviate poverty.