̽��ֱ�� of Cambridge - pig

Pig-borne disease jumped into humans when rearing practices changed

cjb250 — Tue, 31 Mar 2015 09:00:00 +0000

Almost every pig carries harmless strains of the S. suis bacterium – such strains are known as ‘commensal’ strains. However, a more virulent group of strains of the bacteria also exist, which cause disease in pigs worldwide and are a major driver of antibiotic use for prevention. Increasingly, this group of strains is also implicated in serious human diseases such as meningitis and septicaemia.

In order to understand the genetic basis of disease in S. suis, an international study, led by the Bacterial Respiratory Diseases of Pigs-1 Technology (BRaDP1T) consortium, examined the genomes of 375 clinical samples from pigs and humans from the UK and Vietnam and combined these with data already published on 15 S. suis genome sequences and draft genomes from around the world. They found that the commensal strains and disease-causing strains differed genetically; in particular, the disease-causing strains have between 50 and 100 fewer genes than the commensal strains.

Dr Lucy Weinert from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge, first author of the study, says: “It seems that the loss of genes is associated with causing disease. This is something we see quite often in bacteria, but for reasons that are unclear. One possibility is that the missing genes are those that hinder the function of newly-acquired virulence factors in the genomes.”

By examining the S. suis’s ‘tree of life’ – which looks at how the bacteria have evolved over time – the researchers were able to show that the emergence of a group of strains causing meningitis in pigs and the human form of the disease dates back to the 1920s, when pig production was intensified with the introduction of wide-scale indoor rearing of meat-producing pigs in larger groups, supported by government schemes that favoured larger producers with regular throughput. However, despite having jumped the species barrier from pig to human, the bacteria do not appear to have adapted to infect humans.

“A group of more virulent strains seem to have emerged at around the time the pig industry changed, and it is these strains that mostly cause disease in pigs and humans,” says Professor Duncan Maskell, Head of the School of the Biological Sciences at Cambridge.

“Human S. suis disease in the West is extremely rare, but is seen more frequently in south east Asia. It is most likely spread to humans through poor food hygiene practices or other environmental factors. This emphasises the importance of monitoring such practices and putting policies in place to reduce the risk of the spread of infections between species.”

̽��ֱ��study was primarily funded by the Biotechnology and Biological Sciences Research Council.

Reference
Weinert, LA et al. Genomic signatures of human and animal disease in the zoonotic pathogen Streptococcus suis. Nature Communications; 31 March 2015

̽��ֱ��most virulent strains of Streptococcus suis, the leading cause of bacterial meningitis in adult humans in parts of southeast Asia and in pigs around the world, are likely to have evolved and become widespread in pigs at the same time as changes in rearing practices, according to research from an international consortium published today in the journal Nature Communications.

A group of more virulent strains seem to have emerged at around the time the pig industry changed, and it is these strains that mostly cause disease in pigs and humans

Duncan Maskell

Balint Földesi

Pig Head

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Field to fork: safeguarding livestock health

lw355 — Thu, 21 Jul 2011 09:45:03 +0000

About 17 billion chickens, almost 10 billion pigs, and nearly 2 billion each of cattle and sheep were produced as livestock worldwide in 2009. And, by 2050, demand for livestock is projected to double. With the added strain of increasing meat production on resources such as land, water, crops and energy, it’s vital to maximise the ‘output for input’, as Professor Duncan Maskell, Head of Cambridge’s Department of Veterinary Medicine and Marks and Spencer Professor of Farm Animal Health, Food Science and Food Safety, explained: “How you should apportion crops between food for animals and food and fuel for humans is a complex question, so it’s crucial to ensure that resource input counts in terms of output of meat, and one of the main moderators of this relationship is animal welfare, especially in terms of infectious disease.”

Viral epidemics can sweep through livestock, and endemic diseases such as respiratory infections can affect the rate at which animals grow. A further risk to food security is posed by bacterial infections of livestock that contaminate meat and cause food poisoning.

Research at the Department of Veterinary Medicine is tackling disease on all of these fronts in what Professor Maskell has described as “a perfect marriage between fundamental biological research and applied clinical outcomes.”

‘Flu-free’ chickens

A breakthrough was announced earlier this year that could prevent future bird flu outbreaks from spreading within poultry flocks. Dr Laurence Tiley, in collaboration with researchers in the Roslin Institute at the ̽��ֱ�� of Edinburgh, produced the world’s first genetically modified chickens that prevent the spread of avian influenza.

Since 2003, over 300 million poultry have been culled as a result of influenza outbreaks, and in some countries the virus is now endemic in wild bird populations. Preventing virus transmission in chickens would reduce both the economic impact of the disease and the risk for people who are exposed to the infected birds.

̽��ֱ��scientists introduced a new gene that manufactures a ‘decoy’ molecule into the chicken genome. In a clever move to confuse the flu virus into ignoring its own replication needs, the decoy mimics an important control element of the virus and diverts the viral replication machinery away from its own genetic material.

“Because the control element is absolutely conserved across strains, we expect that the decoy will work against all strains of avian influenza and be difficult for the virus to evolve around,” said Dr Tiley, whose research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC). Although the birds become sick themselves, they don’t transmit the infection to other chickens, even those without the decoy molecule.

“At this stage, the chickens are not intended for consumption,” Dr Tiley added. “This genetic modification is a significant first step. Our objective now is to develop chickens that are completely resistant to avian flu.”

Threats from the wild

Viral epidemics are not just a concern in livestock, but also in relation to wildlife, as Professor James Wood explained: “Often, emerging infectious diseases originating from wildlife are a particular challenge because little might be known about the virus, how it’s transmitted to livestock and humans, or the potential for epidemics to spread.”

Nipah virus, for example, was first recognised in 1999 when an outbreak causing severe inflammation of the brain occurred in pigs and pig farmers in Malaysia. When the source of the virus was traced, it was found to be on fruit contaminated by infected fruit bats, the natural host of the virus.

“Bats epitomise the growing challenges associated with the spread of wildlife diseases,” added Professor Wood: “They are associated with a wide range of viruses, live in close proximity to animals and humans, and many important puzzles remain about the social, environmental and biological dynamics that shape pathogen transmission.”

̽��ֱ��first steps to remedy this lack of information were taken last year when a unique network was created comprising experts from institutions worldwide including collaborators in Bangladesh, Ghana and Kenya. ̽��ֱ��consortium was funded by a Catalyst grant from the Medical Research Council and three other research councils.

“ ̽��ֱ��network has a long-term aim of creating vitally needed interdisciplinary knowledge,” said Professor Wood, one of the leaders of the network, “as well as pioneering interventions geared to enabling bats, animals and people to co-exist with reduced disease risk.”

Super-vaccination at one sniff

Respiratory infections in pigs are a major animal welfare issue and cost the pig industry millions of pounds each year. An innovative project has begun the process of developing a ‘super-vaccine’ to guard against infection by the bacteria that are responsible for the most serious infections.

Funded with £5.6 million from the BBSRC, the consortium links experts from the ̽��ֱ�� of Cambridge, Imperial College London (the project co-ordinator), the London School of Hygiene and Tropical Medicine, and the Royal Veterinary College.

Dr Dan Tucker, who together with Professor Maskell leads the Cambridge component of the five-year project, explained why these infections matter so much to food security: “When a pig gets sick it diverts its energy away from growth to fighting off the infection. This requires treatment with antibiotics and decreases the efficiency with which vegetable protein is converted into kilograms of meat.”

̽��ֱ��goal is to create a single super-vaccine that can be administered by nasal spray and protect against Actinobacillus pleuropneumoniae, Haemophilus parasuis, Mycoplasma hyopneumonia/hyorhinis and Streptococcus suis. “Our gold standard would be to create a live vaccine based on a mutated version of one of these bacteria that no longer causes the disease, and then engineer it to display portions of the other three bacteria so that a strong immune response is made to all,” said Dr Tucker.

High-throughout sequencing in collaboration with the Wellcome Trust Sanger Institute is enabling the scientists to assemble the largest ever sequenced collection of these bacteria. ̽��ֱ��team has begun to identify which genes need to be ‘knocked out’ to provide a live vaccine – information that will also help in understanding why some strains cause more virulent disease than others.

Alongside vaccine development, a diagnostic kit will be developed to detect all four pathogens in less than six hours. ̽��ֱ��goal is to have a diagnostic test and potential vaccine ready for field trials at Huazhong Agricultural ̽��ֱ�� in China within three years.

Safety first

Diseases can also be spread by meat. Although the global incidence of food-borne illness is difficult to estimate, up to 30% of the population in industrialised countries may be affected each year according to the World Health Organization.

Salmonella and Campylobacter – two of the most common sources of food-borne disease – are the basis of multiple research programmes at the Department of Veterinary Medicine, such as the research led by Professor Maskell. His team has particularly focused on understanding the dynamics of the interactions of bacteria with their animal hosts.

“Thanks to the completion of genome sequences for many of the chief culprits and the advent of high-throughput sequencing,” said Professor Maskell, “the door has been opened on many of the secrets of how pathogens such as salmonellae cause disease.”

“We are committed to maintaining strong basic research, but do this in the context of finding improved intervention strategies,” he added. “Health standards and life expectancy have gone up globally, and a large part of this is better nutrition. At many levels this means more meat and high-protein food. One key aim of our research is to provide the fundamental knowledge and clinical tools to keep livestock healthy and our food safe.”

For more information, please contact Professor Duncan Maskell (djm47@cam.ac.uk) at the Department of Veterinary Medicine.

Veterinary research in Cambridge is spearheading a new generation of preventive methods to protect livestock from disease.

One key aim of our research is to provide the fundamental knowledge and clinical tools to keep livestock healthy and our food safe.

Professor Duncan Maskell

Norrie Russell, ̽��ֱ��Roslin Institute, ̽��ֱ�� of Edinburgh

Genetically modified chicken

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Towards a ‘super-vaccine’ for swine bacterial diseases

bjb42 — Mon, 01 Mar 2010 09:27:59 +0000

Among the most serious diseases in pigs are those that are caused by bacteria that live in their throats, airways or tonsils and can cause severe lung infections such as pneumonia. Infected animals either die quickly or fail to grow normally, resulting in substantial economic costs to the worldwide pig industry and adding to food security concerns. Because the infections are difficult to diagnose, and current vaccines have limited efficacy, antibiotics are now in widespread use in efforts to reduce infection.

A new five-year, £5.6 million grant awarded by the Biotechnology and Biological Sciences Research Council (BBSRC) under its strategic longer and larger grant (LoLa) scheme, which supports research projects requiring ‘big’ science approaches and longer timescales, aims to develop a new vaccine and a diagnostic tool to combat the four most common bacteria that cause infections in pigs.

̽��ֱ��grant has been awarded to a consortium of researchers at the ̽��ֱ�� of Cambridge, Imperial College London, the London School of Hygiene and Tropical Medicine, and the Royal Veterinary College, as well as Huazhong Agricultural ̽��ֱ�� in China, and involves three UK government-funded agencies. ̽��ֱ��consortium also receives support from Pfizer Animal Health.

‘This combined expertise has generated a new opportunity that is highly synergistic and where real progress is possible,’ said Professor Maskell, Head of the Department of Veterinary Medicine and leader of the Cambridge component. ‘It’s also a perfect marriage between fundamental biological research and applied clinical outcomes.’

‘As a first step, we are isolating bacteria from pigs and assembling the largest ever sequenced collection of these types of bacteria,’ explained co-investigator Dr Dan Tucker. ‘From this, we’ll design and assemble appropriate super-vaccines and single-platform diagnostic tests. Crucially, these will immunise and test pigs for all four pathogens at the same time.’ In the final year of the project, field trials will be carried out in China, where dedicated facilities for this type of work are already set up.

Commenting on the timeliness of the BBSRC funding, Professor Maskell added: ‘Technical innovations and the availability of genome data have progressed to such an extent, and continue to do so, that only recently has it become possible to embark on this type of programme to find effective vaccines and diagnostics.’

For more information, please contact Professor Duncan Maskell (djm47@cam.ac.uk), Marks & Spencer Professor of Farm Animal Health, Food Science and Food Safety at the Department of Veterinary Medicine (www.vet.cam.ac.uk/).

A new multidisciplinary research programme aims to develop a single vaccine that will combat four major respiratory pathogens of pigs.

It’s a perfect marriage between fundamental biological research and applied clinical outcomes.

Professor Duncan Maskell

̽��ֱ��Pug Father from Flickr

Prize Pig

Biotechnology and Biological Sciences Research Council

̽��ֱ��Biotechnology and Biological Sciences Research Council (BBSRC) is the UK’s principal research funder across the biosciences. Its current Chair is Sir Tom Blundell, who is also Director of Research and Emeritus Professor in Cambridge’s Department of Biochemistry.

Over the past decade, BBSRC has helped achieve a step change in bioscience. Descriptive, single-problem research is increasingly being replaced by generic, predictive and systems approaches, informed by the physical, computational and social sciences. ̽��ֱ��result is that the UK has kept its world-lead in fundamental bioscience, and enhanced its capability to generate the new knowledge needed to tackle global challenges such as food security, sustainable energy and healthier ageing.

BBSRC research at Cambridge exemplifies this combination of excellence and impact. A grants and fellowships portfolio of over £50 million supports research in more than 20 departments, ranging from predictive modelling of disease epidemiology, the role of short interfering RNAs in cell regulation, data standards and software for macromolecular analysis, to mechanisms of predator vision and defensive colouration in birds. BBSRC also funds around 100 postgraduate research students including some registered with the ̽��ֱ�� at the Babraham Institute.

Cambridge hosts one of six programmes that comprise the BBSRC Sustainable Bioenergy Centre, which is a £26 million investment bringing together academics and industry to investigate sustainable methods for producing biofuels. Dr Paul Dupree in the Department of Biochemistry leads the Cambridge programme, with partners at Newcastle ̽��ֱ�� and Novozymes A/G, which seeks to improve the release of sugars from plant cell walls. An important resource for the Dupree lab, and many others across Cambridge, has been the protein-analysis capabilities of the Cambridge Centre for Proteomics, a long-term recipient of BBSRC funding.

Research projects requiring ‘big’ science approaches and longer timescales are supported by BBSRC under its strategic longer and larger (LoLa) grant scheme. One such grant to develop a pig super-vaccine was recently awarded to a consortium of researchers based at five universities, including Cambridge’s Department of Veterinary Medicine.

Ways to improve the manufacturability of viral vectors for therapeutics are currently being pursued with funding from the BBSRC-led Bioprocessing Research Industry Club.

BBSRC-funded research at Cambridge has also turned into notable innovations. One example is the massively parallel Solexa sequencing technology invented by Professor Shankar Balasubramanian and Professor David Klenerman in the Department of Chemistry, resulting in the spin-out company Solexa, which was purchased by Illumina for $600 million in 2007. ̽��ֱ��technology is revolutionising bioscience by improving the cost and speed of DNA sequencing by 1,000–10,000 fold on previous technologies. In recognition of this work, Professor Balasubramanian was recently named BBSRC Innovator of the Year 2010.

For more information and to download the BBSRC 2010–2015 Strategic Plan, please visit www.bbsrc.ac.uk/

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