11,000-year-old living dog cancer reveals its secrets
By fpjl2 from University of Cambridge - Department of Veterinary Medicine. Published on Jan 23, 2014.
Scientists have sequenced the genome of the world’s oldest continuously surviving cancer, a transmissible genital cancer that affects dogs.
This cancer, which causes grotesque genital tumours in dogs around the world, first arose in a single dog that lived about 11,000 years ago. The cancer survived after the death of this dog by the transfer of its cancer cells to other dogs during mating.
The genome of this 11,000-year-old cancer carries about two million mutations – many more mutations than are found in most human cancers, the majority of which have between 1,000 and 5,000 mutations. The team used one type of mutation, known to accumulate steadily over time as a “molecular clock”, to estimate that the cancer first arose 11,000 years ago.
“The genome of this remarkable long-lived cancer has demonstrated that, given the right conditions, cancers can continue to survive for more than 10,000 years despite the accumulation of millions of mutations,” said Dr Elizabeth Murchison from Cambridge’s Department of Veterinary Medicine and the Wellcome Trust Sanger Institute, who is lead author on the study, published today in the journal Science.
The genome of the transmissible dog cancer still harbours the genetic variants of the individual dog that first gave rise to the cancer 11,000 years ago. Analysis of these genetic variants revealed that this dog may have resembled an Alaskan Malamute or Husky. It probably had a short, straight coat that was coloured either grey/brown or black. Its genetic sequence could not determine if this dog was a male or a female, but did indicate that it was a relatively inbred individual.
“We do not know why this particular individual gave rise to a transmissible cancer,” said Murchison, “But it is fascinating to look back in time and reconstruct the identity of this ancient dog whose genome is still alive today in the cells of the cancer that it spawned.”
Transmissible dog cancer is a common disease found in dogs around the world today. The genome sequence has helped scientists to further understand how this disease has spread.
“The patterns of genetic variants in tumours from different continents suggested that the cancer existed in one isolated population of dogs for most of its history,” says Dr Murchison. “It spread around the world within the last 500 years, possibly carried by dogs accompanying seafarers on their global explorations during the dawn of the age of exploration.”
Transmissible cancers are extremely rare in nature. Cancers, in humans and animals, arise when a single cell in the body acquires mutations that cause it to produce more copies of itself. Cancer cells often spread to different parts of the body in a process known as metastasis.
However, it is very rare for cancer cells to leave the bodies of their original hosts and to spread to other individuals. Apart from the dog transmissible cancer, the only other known naturally occurring transmissible cancer is an aggressive transmissible facial cancer in Tasmanian devils that is spread by biting.
“The genome of the transmissible dog cancer will help us to understand the processes that allow cancers to become transmissible,” said Professor Sir Mike Stratton, senior author and Director of the Sanger Institute.
“Although transmissible cancers are very rare, we should be prepared in case such a disease emerged in humans or other animals. Furthermore, studying the evolution of this ancient cancer can help us to understand factors driving cancer evolution more generally.”
Inset image: Elizabeth Murchison and Andrea Strakova, University of Cambridge and Genome Research Limited
Genome of longest-living cancer reveals its origin and evolution.
Transmissible cancers in dogs and Tasmanian devils
Join Andrea Strakova for a talk which will reveal unexpected findings about two unique cancers which have adapted to transfer by the means of living cancer cells between their hosts – Tasmanian devils and domestic dogs. We will explore how a cancer can become transmissible, despite the fact that it is usually considered to be a malignant transformation of cells of your own body.
VetCam 2014 course opens for applications
By sjr90 from University of Cambridge - Department of Veterinary Medicine. Published on Jan 16, 2014.
The two-day residential course is designed to give Year 12 students an insight into studying veterinary medicine in general, and also to show the unique benefits of the Cambridge course through a mixture of practical demonstrations, lectures, tours of pre-clinical departments and the Queen’s Veterinary School Hospital.
Attendees stay overnight at Queens’ College for a taste of life as a Cambridge undergraduate.
Georgia, who attended VetCam in 2012 and is now at Pembroke College studying veterinary medicine, said "I heard about VetCam through my sixth form. The bursary place I was given made it possible for me to go without worrying about the cost.
"The two days I spent in Cambridge were really informative. Overall, I learnt a lot about the course and the university as a whole and having this knowledge definitely helped me when it came to applying.
"I applied to Cambridge several months later and now I'm just starting my second term here! Going to VetCam was a really positive experience as it gave me a great insight into life as a vet student here and I haven't looked back since.”
*Please note that the course is now full and all bursaries have been awarded. 18.02.2014
Thanks to continued funding from the University’s Widening Participation Project Fund, a number of bursaries are available to help students from under-represented groups cover the cost of the course.
Fruit bat population covering central Africa is carrier of two deadly viruses
By sj387 from University of Cambridge - Department of Veterinary Medicine. Published on Nov 19, 2013.
The study, conducted jointly by the University of Cambridge and the Zoological Society of London’s Institute of Zoology and published today in the journal Nature Communications, found that the “gregarious” bats span over 4,500 km of central Africa (around the distance from California to New York). The researchers also discovered that thirty-four per cent of the bats had been infected with Lagos bat virus, a disease similar to rabies, and 42 per cent had been infected with henipaviruses.
The African straw-coloured fruit bat (Eidolon helvum), which can live in roosts of over one million and often congregates near cities, was previously known to be a reservoir for these viruses, but it was not known to what extent.
For the study, the researchers tested over 2,000 bats in 12 different countries across Africa, measuring DNA from blood and tissue samples. They discovered that the bats were largely genetically similar, meaning that they travelled and mated across the continent without any evidence of population subgroups or specific migratory patterns – the largest example of this freely mixing population structure ever found in mammals. The species’ homogeneity and extensive movement means that the two viruses can be spread easily.
Professor James Wood, the study’s senior author from the University of Cambridge’s Department of Veterinary Medicine, said: “We now not only know how widespread viral infections are in this bat population, but we also know much more about its population structure. This new information indicates that the unique population of freely mixing bats across the entire continent facilitates the spread of the viruses. This has important implications for the monitoring of these viruses in order to prevent its spread to other animals, including humans.”
Fruit bats are often hunted for meat, a process which can result in a spill-over of these pathogens from animals to humans. Henipaviruses can also be spread through contact with urine and faeces. While no instances of either disease have been reported in humans in Africa, the viruses have previously been detected in pigs in Ghana. Henipaviruses have caused fatal disease in humans, pigs and horses in SE Asia and Australia.
Although potential human infection raises public health concerns, the study’s lead author, Dr Alison Peel, cautions restraint. She said: “Sometimes, a knee-jerk response can be to try and remove bats from urban areas via culling or dispersal. However, there is evidence to suggest that actions such as this can stress the bats and lead to a greater risk of spill-over. The most appropriate response is ongoing studies and public awareness to avoid handling bats, and to wash the wound thoroughly if you are bitten by a bat.”
A population of fruit bats which is found across much of continental Africa is widely infected with two deadly viruses that could spread to humans, new research reveals.
Sustainable livestock production is possible
By gm349 from University of Cambridge - Department of Veterinary Medicine. Published on Sep 25, 2013.
Consumers are increasingly demanding higher standards for how their meat is sourced, with animal welfare and the impact on the environment factoring in many purchases. Unfortunately, many widely-used livestock production methods are currently unsustainable. However, new research out today from the University of Cambridge has identified what may be the future of sustainable livestock production: silvopastoral systems which include shrubs and trees with edible leaves or fruits as well as herbage.
Professor Donald Broom, from the University of Cambridge, who led the research said: “Consumers are now demanding more sustainable and ethically sourced food, including production without negative impacts on animal welfare, the environment and the livelihood of poor producers. Silvopastoral systems address all of these concerns with the added benefit of increased production in the long term.”
Current cattle production mostly occurs on cleared pastures with only herbaceous plants, such as grasses, grown as food for the cows. The effects on the local environment include the removal of trees and shrubs as well as the increased use of herbicides, all of which result in a dramatic decrease in biodiversity. Additionally, there is also contamination of soil and waterways by agricultural chemicals as well as carbon costs because of vehicles and artificial fertiliser necessary to maintain the pasture.
The researchers advocate that using a diverse group of edible plants such as that in a silvopastoral landscape promotes healthy soil with better water retention (and less runoff), encourages predators of harmful animals, minimizes greenhouse gas emissions, improves job satisfaction for farm workers, reduces injury and stress in animals, improves welfare and encourages biodiversity using native shrubs and trees.
Additionally, shrubs and trees with edible leaves and shoots, along with pasture plants, produce more food for animals per unit area of land than pasture plants alone. Trees and shrubs have the added benefit of providing shade from hot sun and shelter from rain. It also reduces stress by enabling the animals to hide from perceived danger.
“The planting as forage plants of both shrubs and trees whose leaves and small branches can be consumed by farmed animals can transform the prospects of obtaining sustainable animal production,” said Professor Broom. “Such planting of ‘fodder trees’ has already been successful in several countries, including the plant Chamaecytisus palmensis which is now widely used for cattle feed in Australia.”
Another success has been in Colombia where a mixed planting of the shrub Leucaena with a common pasture grass resulted in a 27% increase in dry matter for food and 64% increase of protein production.
When ruminants, such as cows, goats and sheep, are consuming the plants from a silvopastoral system, researchers have seen an increase in growth and milk production. Milk production in the tropical silvopastoral system mentioned above was 4.13 kg per cow when compared with 3.5 kg per day on pasture-only systems. As the numbers of animals per hectare was much greater, production of good quality milk per hectare was four to five times greater on the silvopastoral system.
One of the additional benefits of using the silvopastoral system is that it increases biodiversity. Biodiversity is declining across the globe, and the main culprit is farming – 33% of the total land surface of the world is used for livestock production. If farmers were to switch to sustainable livestock production methods, such as the silvopastoral system, the result would be much greater biodiversity with no increase in land use.
Professor Broom added: “It is clear that silvopastoral systems increase biodiversity, improve animal welfare and provide good working conditions while enabling a profitable farming business. The next step is to get farmers to adopt this proven, sustainable model.”
The paper ‘Sustainable, efficient livestock production with high biodiversity and good welfare for animals’ was published today, 25 September, in the journal Proceedings of the Royal Society B.
New research advocates use of pastures with shrubs and trees as it is more sustainable, improving animal welfare and increasing biodiversity.
New research reveals how cat dander triggers allergic responses
By amb94 from University of Cambridge - Department of Veterinary Medicine. Published on Jul 24, 2013.
New research reveals how the most common cause of severe allergic reactions to cats, the Fel d 1 protein which is found in cat dander, triggers an allergic response.
Scientists have discovered that when the cat protein Fel d 1 is in the presence of very low doses of the ubiquitous environmental bacterial toxin, lipopolysaccharide (LPS), it activates the pathogen recognition receptor Toll-like receptor 4. Until now, it was not understood how Fel d 1 generated such a large inflammatory response in the immune system.
Allergic reactions are the result of the immune system overreacting to a perceived danger. Instead of identifying and responding to a harmful virus or bacteria, it misidentifies different allergens, including dander (microscopic pieces of animal skin often accompanied by dried saliva from grooming), as dangerous and mounts an immune response.
In order to find out how Fel d 1 triggers these allergic reactions, the researchers exposed human cells to cat and dog dander proteins in the presence or absence of low levels of LPS. The researchers found that when the bacterial toxin LPS is present, it increases the signalling to the body’s immune system, intensifying the body’s inflammatory response to the cat protein Fel d 1.
They also discovered that the part of the immune system that recognises the LPS contaminated Fel d 1 is the pathogen recognition receptor Toll-like receptor 4 (TLR4). (TLR4 also plays a role in a heightened immune response, and subsequent allergic reaction, to dust mite allergens and as well as the metal nickel.) The researchers then used a drug which inhibits the TLR4 response and found that it blocks the effects of the cat dander protein on human cells, thereby preventing an inflammatory response.
Dr Clare Bryant, lead author of the research from the University of Cambridge’s Department of Veterinary Medicine, said: “How cat dander causes such a severe allergic reaction in some people has long been a mystery. Not only did we find out that LPS exacerbates the immune response’s reaction to cat dander, we identified the part of immune system that recognises it, the receptor TLR4.”
Additional research revealed that the dog allergen Can f 6 (a protein found in dog dander) also enhances LPS-induced activation of TLR4. The researchers believe that dog-allergy sufferers could also benefit from new drugs which inhibit TLR4.
Dr Bryant continued: “As drugs have already been developed to inhibit the receptor TLR4, we are hopeful that our research will lead to new and improved treatments for cat and possibly dog allergy sufferers.”
The research was funded by the Wellcome Trust and the Medical Research Council (MRC). It was published in the The Journal of Immunology.
For more information about this story, please contact: Genevieve Maul, Office of Communications, University of Cambridge. Email: Genevieve.Maul@admin.cam.ac.uk; Tel: 01223 765542.
Immune system’s extreme reaction to cat allergen previously poorly understood; study could lead to new treatments for those with cat and dog allergies
African Horse Sickness: mapping how a deadly disease might spread in the UK
By amb206 from University of Cambridge - Department of Veterinary Medicine. Published on May 25, 2013.
As its name suggests, African Horse Sickness (AHS) is associated with the continent of Africa, where it is feared as a deadly disease. It has long been assumed by British veterinarians and horse-owners that the disease, which is carried by midges, could not spread to cooler northern climates.
But researchers now think that its arrival in northern Europe could be only a matter of time – and perhaps more importantly, that it could spread if it did arrive.
A study undertaken by scientists at the University of Cambridge Department of Veterinary Medicine, in collaboration with the Animal Health Trust and The Pirbright Institute, shows how dangerous it could be for the horse and pony population if AHS was introduced into the UK. The research also identified which regions would be worst hit at different times of the year.
This information could be vital to strategies for coping with an outbreak if it arrived. The study also emphasises the importance of the continued exclusion of the disease.
The research was led by Dr Gianni Lo Iacono, a multidisciplinary scientist whose expertise lies in the mathematical modelling of a range of problems related to the interface between biology and physics. He worked with a team of colleagues from complementary fields including Professor James Wood, a renowned specialist in infectious diseases.
Most strikingly, East Anglia emerges from the study as the region that is most vulnerable to AHS spread which could occur if the disease was not identified early enough for action to be taken to contain it.
In Africa, the disease is spread by infected insects from species of midge known as Culicoides imicola, which carry the African Horse Sickness virus, an orbivirus of the family Reoviridae. Once a horse is infected by AHS, there is no treatment and no cure: the animal will have a high fever within 24 hours and most infected animals will be dead within 48 hours.
Other equidae, zebras and donkeys, are susceptible to AHS infection but do not have such severe disease. Infected zebras do not exhibit any apparent symptoms: as seemingly healthy animals they are potentially lethal carriers. Donkeys develop symptoms but can survive the disease.
First recorded references of AHS occurred in 1327 in Yemen, and in the mid-1600s following the introduction of horses to southern Africa. The disease was clearly identified by the British Army in South Africa 150 years ago when scores of cavalry horses perished in an epidemic.
Ever since, European horse owners have taken comfort from the fact that the disease could not strike in cooler countries. The British climate was considered too cold for the Culicoides imicola midges to survive. On top of this, the UK (and Europe more generally) has protective mechanisms in place that prohibit horses from Africa entering the country.
A growing number of veterinarians now believe that AHS can now arrive in the UK. Well-documented outbreaks were reported in Morocco (1965, 1989–1991), Spain (1987, 1988,1990) and Portugal (1989). The British climate is warming and global transportation of perishable fresh goods – such as flowers and vegetables – offers a possible route for infected midges to enter the country.
The prospect of AHS brings sharply into focus the need for greater research into ways of preventing an incursion of AHS – and ways to cope in the event of an outbreak. “Our work demonstrates that there is no place for complacency about the ability of the virus to spread here,” said Professor Wood.
A greater understanding of AHS requires a multi-stranded approach covering the behaviour and life cycle of the midge and the geographical distribution and movement of horses, plus possible routes for infection to enter the country. Midge numbers and activity are highest during the warmer summer months, when the arrival of infection from overseas would be most serious.
In the UK, all horses have passports as a legal requirement but these documents record the owners’ address rather than the location where their animals are kept. If horses were mapped according to their owners address, London, for example, would emerge as the centre with the densest horse population. Clearly most horses owned by Londoners are kept outside the city, many of them within easy driving distance of their owners’ homes.
Correcting this issue posed problems. However, satellite data on land usage and a survey which recorded the distribution of distances between horses and their owners in different land-use settings (people live closer to their horses in rural areas than they do in urban areas) allowed the researchers to produce a more meaningful map of the risk of the disease. This showed that East Anglia is particularly vulnerable to an outbreak: not only is the region warm and dry, but it also has distinct clusters of horses, notably around Newmarket.
The team has also investigated another important aspect of the disease: the possible 'dilution effect' that could be achieved through keeping animals not susceptible to the virus, such as cattle and sheep, close to horses.
Dr Lo Iacono explained: “In some communities in Africa people keep cattle or sheep near their houses in the belief that this will distract mosquitoes carrying malaria away from people. Some midges show apparent preference for cattle over sheep, so in South Africa deploying cattle to protect sheep from bluetongue (a similar disease to AHS in cattle and sheep) has been proposed as a way to control the disease. On the other hand, the presence of other species might well prove to be an added attraction for midges, exacerbating the threat to horses.”
The research re-emphasises the importance of veterinary education to allow early disease identification, which can reduce the critically important reaction times to allow optimal control.
The tools that Dr Lo Iacono has developed have potential applications in mapping and responding to the spread of other diseases, some of which are ecologically even more complex – such as Rift Valley Fever, a mosquito-borne disease that affects both humans and animals, causing a serious disease and in some cases death.
The research provides a good example of how theoretical models can identify biological knowledge gaps (identifying midge biting preferences). This is now being taken forward in other studies.
‘Where are the horses? With the sheep or cows? Uncertain host location, vector-feeding preferences and the risk of African horse sickness transmission in Great Britain’ by Giovanni Lo Iacono, Charlotte Robin, Richard Newton, Simon Gubbins, and James Wood is published by the Journal of the Royal Society, Interface (2013) 20130194 doi:10 .1098/rsif.2013.0194
For more information on this story contact Alex Buxton, Office of Communications, University of Cambridge firstname.lastname@example.org 01223 761673.
A disease lethal to horses, until now confined to hot countries, could arrive in the UK. New research creates a picture of its possible spread and pinpoints the area that would be worse hit.
New study shows how Salmonella colonises the gut
By ns480 from University of Cambridge - Department of Veterinary Medicine. Published on Apr 19, 2013.
Salmonella is a major cause of human diarrhoeal infections and is frequently acquired from chickens, pigs and cattle, or their products. Around 94 million such infections occur in people worldwide each year, with approximately 50,000 cases in the UK per annum.
In a BBSRC-funded collaboration between the University of Cambridge’s Department of Veterinary Medicine, the University of Edinburgh’s Roslin Institute and the Wellcome Trust Sanger Institute, scientists have studied how Salmonella colonises the intestines of food-producing animals. This is relevant both to the welfare of the animal hosts and to contamination of the food chain and farm environment.
To unravel how Salmonella persists in farm animals, the scientists studied the role of thousands of its genes. Using a novel DNA-sequencing method the team screened 10,000 mutants of Salmonella for their ability to colonise the guts of chickens, pigs and cattle. This was achieved by using a novel technique based on high-throughput DNA sequencing which enabled the screening of 475 mutants of the bacteria per single animal. In the process, they assigned roles in infection to over 2700 Salmonella genes in each of the farm animal hosts. This has yielded roles for over half the genetic instructions of the bacterium and is by far the most comprehensive survey for any pathogen in its natural hosts to date.
Professor Duncan Maskell at the University of Cambridge said, “We found that hundreds of genes are important for colonisation; this provides vital new data for the design of strategies to control Salmonella in animals and reduce transmission to humans. Our data indicate that Salmonella contains a core set of genes that is important when it infects all three hosts, but that there are smaller sets of genes that are required for infection of each individual host species.”
Professor Mark Stevens at The Roslin Institute added, “We are always trying to develop new ways of reducing the number of animals used in experiments. The methods we applied allowed us to survey the fate of hundreds of bacterial mutants simultaneously in one animal, rather than us having to test them one-by-one. This represents a significant advance in the study of microbial diseases, and can be applied to other pathogens and host animals.”
The team now plans to use the data it has collected to design vaccines or treatments to reduce the burden of salmonellosis in animals and humans.
Researchers plan to use data collected to develop vaccines to control Salmonella in animals and humans
New research suggests animal-to-human transmission of MRSA
By gm349 from University of Cambridge - Department of Veterinary Medicine. Published on Mar 25, 2013.
Cambridge scientists have linked two human cases of infection with the antibiotic- resistant superbug MRSA to farms in Denmark. The results of the study, published today in the journal EMBO Molecular Medicine, suggest the methicillin-resistant Staphylococcus aureus (MRSA) bacteria was transmitted from the livestock to the farmers.
The type of MRSA which was found in both of the human cases was only discovered two years ago by Dr Mark Holmes and his colleagues from the University of Cambridge. The new strain’s genetic makeup differs greatly from previous strains, which means that the ‘gold standard’ molecular tests currently used to identify MRSA - a polymerase chain reaction technique (PCR) and slide agglutination testing - do not detect it.
For this study, the scientists used whole genome sequencing to investigate two cases of the new MRSA where the patients lived on farms to see if the same strain could be found in the animals on the farm.
Dr Holmes, from Cambridge’s Department of Veterinary Medicine and the senior author on the paper, said: “Having found this new MRSA in both people and animals on the same farm it was likely that it is being transmitted between animals and people.
“By looking at the single differences in nucleotides, or SNPs, in the DNA sequences of each isolate, it became obvious that in both farms we looked at the human and animal MRSA were almost identical. In one case, the results also clearly showed that the most likely direction of transmission was from animal to human.”
The study raises questions about whether cows could be a reservoir for new strains of MRSA. It was previously not clear whether MRSA was transmitted to cows from humans or to humans from cows, but the new research indicates that the livestock is the likely source of these new strains.
“Our findings demonstrate that the MRSA strains we studied are capable of transmission between animals and humans, which highlights the role of livestock as a potential reservoir of antibiotic resistant bacteria,” remarked Dr Ewan Harrison, a post-doctoral research associate at the University of Cambridge’s Department of Veterinary Medicine and co-author of the paper.
For more information about this story, please contact: Genevieve Maul, Office of Communications, University of Cambridge. Email: Genevieve.Maul@admin.cam.ac.uk; Tel: 01223 765542.
Using whole genome sequencing, scientists have found two independent human cases of infection have been linked to livestock.
March of the superbugs
By admin from University of Cambridge - Department of Veterinary Medicine. Published on Feb 13, 2013.
Every so often, research laboratories and hospitals testing patients for the superbug methicillin-resistant Staphylococcus aureus (MRSA) have come across an oddity: a strain that appeared to be MRSA because it was resistant to antibiotics but one that tested negative with the ‘gold standard’ molecular test. The quirky cases were so infrequent that they were usually filed away for future analysis or disregarded. Until, that is, PhD student Laura Garcia-Alvarez from Cambridge’s Department of Veterinary Medicine had the tenacity to look a little further at a bacterial strain she had spotted in cows’ milk.
MRSA first appeared in 1961 and epidemic strains of this difficult-to-treat bacterium have since spread worldwide in hospitals and the community. In the farming world, MRSA causes bovine mastitis – an infection of cows’ udders – affecting both animal welfare and milk yields.
Garcia-Alvarez was working with Dr Mark Holmes on bovine mastitis when she came across one of the ‘curious anomalies’. The strain was resistant to antibiotics but in the standard molecular test was negative for the presence of mecA – the gene responsible for methicillin resistance. She had the isolates retested and then sequenced at the Wellcome Trust Sanger Institute.
It turned out that she had discovered a new strain of MRSA. Its antibiotic resistance is carried not by mecA but by mecC, a gene that is so genetically dissimilar to mecA that it can’t be picked up by the standard molecular test used to define MRSA but only by DNA sequencing.
As Holmes and Garcia-Alvarez began to spread the information to colleagues around Europe, it soon became clear that this phenomenon was not confined to cows: others had found the unusual samples in humans. “We started to get calls from hospitals and research groups who had come across a small number of human MRSA strains that behaved differently,” said Holmes. “Within a few weeks, we had a further 50 isolates. This meant that what we were looking at was a human problem too.”
Garcia-Alvarez, who at the time was a student on the Department’s postgraduate training in infectious disease dynamics programme, described how finding the same new strain in both humans and cows was worrying, although no cause for immediate alarm: “Pasteurisation of milk will prevent any risk of infection via the food chain. In the wider UK community, less than 3% of individuals carry MRSA – typically in their noses – without becoming ill.”
“Nonetheless,” added Holmes, “MRSA presents a major challenge to the control of infectious diseases. Finding a new strain – studying its prevalence, how it confers antibiotic resistance and how it’s transmitted – can tell us enormous amounts about the origins and evolution of antibiotic resistance.”
Since the discovery, Holmes’ team has been investigating the prevalence of the strain in human and animal populations – and the potential for passing the strain between species – in partnership with Cambridge’s Department of Medicine, the Sanger Institute and the Moredun Research Institute (Scotland), and funded by the Medical Research Council.
One of their first steps was to develop a better genetic test, one that also detected the new strain. The timing was fortuitous. Moves to help hospitals identify MRSA more quickly have resulted in the development of automated systems based on genetic testing. Because the standard genetic test does not detect the new strain, the scientists have now developed a protocol that will pick up both strains.
Moreover, their recent research has shown that additional MRSA strains have emerged that possess other mechanisms of antibiotic resistance: “We’ve found about 40 human MRSA isolates that don’t have a mecA or a mecC gene, and we are trying to establish why these are resistant to methicillin-family antibiotics. In retrospect, it was incredibly lucky that the original isolate we investigated happened to have a genetic variation in a known gene that could be picked up by whole genome sequencing.”
To identify how mecC confers antibiotic resistance, Holmes collaborated with Professor Alexander Tomasz at Rockefeller University, New York. They discovered that the gene is more resistant than mecA to cefoxitin (one of the newer classes of antibiotics): “Inappropriate use of antibiotics in human and veterinary medicine has favoured the selection and growth of antibiotic-resistant microorganisms,” explained Holmes. “Our finding suggests that an increased use of this drug may have driven emergence of the new strain.”
“We also now know that the new strain is found in almost every species that we’ve studied, including domestic cats and dogs, wild rats, deer, a rabbit, a common seal, sheep and a chaffinch. The bacterium may have lost factors that restricted it to certain species, or gained pan-host virulence factors that make it better able to colonise multiple species. We need to know how and why this has happened to understand the emergence of bacterial pathogens from animals and their dissemination into human populations.”
Now, their latest research has tracked transmission of the superbug, providing the first direct evidence of transmission of the new strain between livestock and humans.
The researchers capitalised on a growing trend to use increasingly rapid and affordable DNA sequencing for tracking the transmission of pathogens. This technique is helping scientists to look for differences at the level of single letters in the genetic code as a means to map the direction of infection – from patient to patient, and from one animal species to another. The team investigated two cases of mecC MRSA in Danish farmers. The strains circulating in the farmers’ livestock and those isolated from the patients only differed by a small number of letters – strong evidence that the farmers had acquired their infections from their animals, in one case a sheep and in another a cow.
“The ability to confirm animal-to-human transmission in virtual real time using this technology can’t be underestimated,” said Holmes. “High-throughput DNA sequencing is going to revolutionise clinical microbiology by enabling targeted epidemiological follow-up and infection control.”
Nearing the precipice
Mastitis is the most common infectious disease of dairy cattle, affecting the welfare of cows and, according to one estimate, costs the UK dairy industry around £170 million per year. Its control and treatment relies on the use of millions of doses of therapeutic and prophylactic antibiotics every year. “Our research on MRSA is pointing to the fact that although we are not on the precipice of having the whole system collapse through selection of bugs that are even more resistant or having husbandry systems that make it impossible to eliminate them, we are closer to the precipice than we would like to be,” said Holmes. “As it is, S. aureus is considered impossible to eliminate in dairy herds – you have to live with it once you’ve got it. “Farmers and veterinarians are in a constant battle to improve the health of dairy cows, yet farming cannot be sustained at these levels if it is generating these types of resistance. Moreover, we can’t predict how these bacterial strains will evolve – they could become more resistant, more virulent or better able to jump between species.”
Holmes views the interface between veterinary medicine and human medicine as crucial to understanding infectious diseases such as MRSA: “There is very little research on S. aureus mastitis in cows in comparison to research into it as a human pathogen, and yet now we’re beginning to see exactly the same organism being found in people and in cows. This means that we should be thinking about the epidemiology of disease control and the development of antibiotic resistance in both species. Understanding how new strains emerge will help us to understand the growing public health problem of antibiotic resistance.”
For more information, please contact Louise Walsh at the University of Cambridge Office of External Affairs and Communications.
Scientists who recently discovered a new strain of superbug have now tracked its transmission between animals and humans.
Cambridge researchers support the WHO
By lw355 from University of Cambridge - Department of Veterinary Medicine. Published on Dec 20, 2012.
The WHO Collaborating Centre for Modelling, Evolution and Control of Emerging Infectious Diseases recognises the work of Cambridge researchers who work in this area.
The Centre, directed by Professor Derek Smith in the Department of Zoology, has pan-university and highly interdisciplinary activities with members of the Department of Zoology, Department of Pathology and Department of Veterinary Medicine in the School of Biological Sciences, members of the School of Clinical Medicine, and also from the Department of Architecture and Computer Laboratory.
The Centre is linked with researchers throughout the world and is concerned with global infectious disease issues that affect not only the developed world, but also the developing world. For example the Centre has close cooperation with the Cambridge in Africa program, in particular on researching the dengue virus.
One of the long-standing activities of the Collaborating Centre is to provide support for WHO activities in the global surveillance of influenza and other pathogens – including dengue and enterovirus 71 – as well as recommendations on suitable vaccine strains for use in these and other emerging and re-emerging diseases.
Each year, influenza infects 5–15% of the world’s population and kills up to half a million people – a figure that can rise to many millions in the event of a pandemic. Spearheading the annual race to identify the best vaccine to combat seasonal flu, the WHO collates information about the flu viruses in circulation worldwide in the preceding months.
As part of this process, Dr Colin Russell in the Department of Zoology curates a global database of information on the rapidly changing variations (called antigenic differences) in the influenza coat protein – the part that makes it difficult for our immune system to recognise flu from one year to the next.
“Our WHO Collaborating Centre is in the privileged position of informing public health initiatives through highly translational scientific research, using technology that allows real-time detection of circulating viruses that escape protection conferred by current vaccines,” said Smith.
The Centre uses a technique called antigenic cartography developed by Smith with Dr Alan Lapedes (Los Alamos National Laboratory, New Mexico) and Professor Ron Fouchier (Erasmus Medical Center, Rotterdam). The technique analyses antigenic differences between pathogens, allowing real-time detection of circulating viruses that escape protection conferred by current vaccine strains. “Antigenic maps allow us to make sense of vast amounts of difficult binding assay data. One can see at a glance the global picture of decades of viral evolution,” added Smith.
In addition, the Centre carries out research on the evolution of pandemic influenza. “We can start asking questions such as how close is nature to evolving an aerosol-transmissible form of bird flu that can be transmitted from human to human, as opposed to the varieties we have seen so far that have been passed to individuals in close contact with infected birds,” said Smith.
The work of the Centre is underpinned by the activities of Cambridge Infectious Diseases, a multidisciplinary community of researchers that promotes, develops and supports initiatives which focus on infectious diseases.
WHO Collaborating Centres are designated by the WHO Director-General to carry out activities in support of the Organization’s programmes on areas such as nursing, occupational health, communicable diseases, nutrition, mental health, chronic diseases and health technologies.
For more information, please visit www.whocc.infectiousdisease.cam.ac.uk/ or download the WHO Collaborating Centre for Modelling, Evolution and Control of Emerging Infectious Diseases brochure.
A newly designated Collaborating Centre at the University of Cambridge will support the World Health Organization (WHO) in detecting and responding to major epidemic- and pandemic-prone diseases.