High resolution phylogenetic analysis of livestock-associated Staphylococcus aureus.

An understanding of the basis for the emergence of endemic diseases of livestock is critical for designing new approaches for their control and to prevent new pathogens from emerging. In particular, the role of human activities such as industrialization and globalization in the evolution of pathogens has not been well examined to date. Staphylococcus aureus is notorious as a major human pathogen and is also an important pathogen of farmed animals including cows, sheep, goats, poultry and pigs, resulting in huge economic losses. Recent studies have provided evidence that S. aureus strains affecting livestock have evolved from human strains and have undergone genetic adaptation to cause endemic diseases of animals. Furthermore, some livestock-associated strains have the capacity to cause zoonotic infections of humans. In the current project we will use high throughput sequencing technology to achieve a comprehensive genetic analysis of livestock-associated S. aureus. The project will reveal the evolutionary origin of livestock-associated S. aureus, how they have adapted to animal hosts, and their potential to cause human infections. The genetic analyses will also facilitate the identification of targets for developing new approaches to controlling endemic livestock disease. Overall, the project will contribute important new insights into a critical animal welfare, food security and public health issue.

The emergence of pathogens causing endemic diseases of livestock is an important food security and public health issue. Staphylococcus aureus is an important human and animal pathogen and a major economic burden worldwide. Recent studies indicate that some animal-specific lineages have evolved from human progenitor strains followed by host-adaptive diversification. Importantly, human activities such as domestication and globalization may have contributed to the emergence of livestock-associated S. aureus by providing increased opportunities for cross-species host-jumps and promoting global dissemination. Furthermore, reports that some livestock-associated strains have the capacity to cause human zoonotic infection is a major public health concern. The project represents a high resolution genetic analysis of livestock-associated S. aureus to resolve the evolutionary history of all major livestock-associated S. aureus, including the molecular basis for host adaptation and the timing of predicted host-jumps. For clonal complexes associated with multiple animal and human hosts, this approach will allow us to identify intraclonal genetic variation, determine the geographic distribution of subtypes, and predict their zoonotic potential. Furthermore, the fundamental molecular processes contributing to adaptive genome diversification will be examined and genetic markers for host-specificity identified, leading to the identification of novel targets for the control of S. aureus livestock diseases. Overall, the project will contribute fundamental insights into an endemic pathogen of livestock which could be applied to improve animal health, and protect food security and public health

It is anticipated that there will be a broad-ranging array of beneficiaries of the proposed project. In the commercial sector, companies involved in the breeding and distribution of broiler poultry and other livestock will benefit from an understanding of of the source of endemic pathogens and how they are disseminated. In a recent paper, we demonstrated that infections of broiler poultry were caused by resident S. aureus of human evolutionary origin which were being disseminated globally. We suggested that decolonization of birds should result in fewer infections. We expect that the findings relating to other livestock S. aureus resulting from the current study would inform on ways to reduce transmission of infections of those species which would be of interest to livestock breeders and farmers. Furthermore, policymakers involved in the regulation of livestock trade would benefit from an improved understanding of the role of industry in the dissemination of pathogens. Policymakers concerned with food safety including the UK Food Standards Agency and the European Food Safety Authority would benefit from our data relating to the prevalence of S. aureus strains on livestock and their potential to cause disease of humans. In addition, if livestock S. aureus is discovered to be a major potential source of new virulent strains affecting humans, the data could be used by bodies such as the UK Health Protection Agency which aims to provide integrated support to limit the dangers to human health from infections including S. aureus. In turn, the general public and particularly those most susceptible to S. aureus infection would benefit. We would anticipate that the research would directly impact on animal health by informing ways to prevent the spread of livestock pathogens and to prevent the emergence of new pathogens affecting livestock. In addition, although beyond the scope of the current proposal, the research could ultimately result in the design of novel therapeutics for controlling diseases such as mastitis of cows, sheep and goats, and skeletal infections of poultry. Accordingly, pharmaceutical companies developing products for animal health could directly benefit from the research. In turn this would generate wealth and contribute to the UK economy. The research will provide new information relating to the basis for the emergence of pathogens and thus could ultimately contribute to approaches to conserving global food security.