The threat posed by the Noble False Widow spider has been debated among spider and healthcare specialists for many years. This new study, published in the international medical journal Clinical Toxicology, confirms that some bite victims experience symptoms very similar to the true black widow spiders and some severe cases require hospitalisation.

Originating from Madeira and the Canary Islands, the Noble False Widow spider Steatoda nobilis, now has the potential to become one of the world’s most invasive species of spider. It was first documented in Britain over 140 years ago, but in recent decades the species has suddenly increased in numbers, significantly expanding its range and density.

The reasons behind this sudden expansion are not clear. Scientists have ruled out climate change as the likely cause but have suggested that a new genetic mutation within the species may have made Noble False Widows more adaptable to new environments. In addition, the species has benefited from an ever-increasing globalised economy, hitchhiking in containers and crates throughout the globe. Human movement has largely contributed to spread this species throughout Europe, North Africa, West Asia and parts of North and South America.

In parts of Ireland and Britain, it has become one of the most common species of spiders found in and around urban habitats. With the increase in False Widow spiders around homes, bites are becoming more prevalent, and scientists are now beginning to realise the full medical importance of these spiders.

Envenomation symptoms can be both localised and systemic, ranging from mild to debilitating pain and mild to intense swelling. Some victims have experienced tremors, reduced or elevated blood pressure, nausea and impaired mobility. In rare instances, victims have developed minor wounds at the bite site or had to be treated for severe bacterial infections.

The research team at NUI Galway have established a DNA database to allow clinicians dealing with cases to confirm the species identity using genetic analysis. This is especially important when the spider has been squashed so an accurate identification of the spider can be made. The study also provides epidemiology of bites which reveals that almost all bites occurred in and around the home, and 88% of bites occurred when the victim was either asleep in bed or when the spider was trapped in clothing. The team are encouraging members of the public to email them at falsewidow@nuigalway.ie if they think they may have been bitten.

Dr Michel Dugon, Head of the Venom Systems Lab at NUI Galway and senior author of the study, said: “In addition to their medically significant venom, Noble False Widows are extremely adaptable and competitive in the wild. Two decades ago, this species was almost unknown in Ireland, the UK or in continental Europe. We still have much to learn about its genetics, origin, behaviour and development. One thing is certain though: this species is here to stay, and we must learn how to live with it.”

Dr John Dunbar, Postdoctoral Researcher at the Venom Systems Lab at NUI Galway and lead author of the study, said: “Speculations around the potential severity of the bites by the Noble False Widow have been debated for many years. We only compiled envenomation cases where we had a clear identification of the spider responsible for the bite. We had to rely on DNA extraction and genetic profiling to confirm some cases. We are encouraging people to capture a photograph of the spider immediately after being bitten. Our latest study confirms without a doubt that Noble False Widows can cause severe envenomations (the process by which venom is injected).

“This species is increasing its range and population density which will undoubtedly lead to an increase in bites (since submitting our study in March we have already received further confirmed bite cases). While most cases will have a mild outcome, we need to continue to closely monitor bites by the Noble False Widow to understand the potential range of symptoms and to treat severe cases when they occur.”

Aiste Vitkauskaite, MSc student in Toxicology at NUI Galway and joint lead in the study, said: “Approximately ten species of Irish spiders have fangs large enough to bite through human skin, yet over the past five years, we have never heard of anybody being bitten by any of the native species. Within the same period, we have recorded dozens of confirmed or probable False Widow bites. These spiders will become increasingly common and so will their bites.”

Professor Derek O’Keeffe, Professor of Medical Device Technology at NUI Galway and Consultant Physician, University Hospital Galway said: “This innovative research led by Dr Dugon and his team clearly demonstrates that Noble False Widow spider bites may result in significant patient morbidity that requires hospital care. This is important as previously we only had anecdotal evidence of its potential harms in victims and therefore this new evidence will allow the updating of clinical guidelines and protocols. These findings demonstrates the key importance of interdisciplinary collaboration between scientists and clinicians to improve patient care.”

The study, published today (26 May 2021) in Nature, is the first successful attempt to induce apparently sterile immunity against a trypanosome parasite. A vaccine was long thought impossible due to the sophisticated ability of the parasites to evade the host immune system. As well as a strong vaccine target for AAT, the findings raise the possibility of identifying vaccine targets for trypanosome species that cause the deadly human infections sleeping sickness and Chagas’ disease.

Animal African trypanosomiasis (AAT) is a disease affecting livestock in Africa and, more recently, South America. It is caused by several species of Trypanosoma parasite, which are transmitted by tsetse flies, causing animals to suffer from fever, weakness, lethargy and anaemia. The resulting weight loss, low fertility and reduced milk yields have a huge economic impact on the people who depend on these animals. The disease has been said to lie at the heart of poverty in Africa1.

In humans, a disease called sleeping sickness is caused by infection with another trypanosome species, Trypanosoma brucei. Although control efforts have reduced the number of infections each year considerably, 65 million people remain at risk. In South America, the potentially life-threatening infection Chagas’ disease is caused by Trypanosoma cruzi and affects at least 6 million people living in endemic areas2.

All trypanosome species have developed sophisticated anti-immune mechanisms that allow the parasites to thrive in their host. For example, African trypanosomes display a protein on their surface that constantly changes and prevents host antibodies from recognising the pathogen. Until now, it was thought impossible to vaccinate against trypanosome infection for this reason.

In this study, scientists at the Wellcome Sanger Institute analysed the genome of T. vivax to identify 60 cell surface proteins that could be viable vaccine targets. Each protein was produced using mammalian cell lines and then used to vaccinate mice to determine if the host immune system had been instructed to identify and destroy the T. vivax parasite.

One cell surface protein, named ‘invariant flagellum antigen from T. vivax’ (IFX), was observed to confer immunity against infection in almost all vaccinated mice for at least 170 days after experimental challenge with T. vivax parasites.

Dr Delphine Autheman, first author of the study from the Wellcome Sanger Institute, said: “Scientists have been searching for a way to vaccinate against animal African trypanosomiasis (AAT) since the parasite and vector were first discovered in the early 20th century. We’ve heard a lot about vaccines recently, but compared to a virus protozoan parasites have a huge number of proteins, making it very difficult to identify the right targets. Several of the 60 targets we tested elicited a partial immune response, but only one conferred the long-lasting protection that makes it a promising vaccine candidate.”

Though drugs exist to prevent or treat AAT, many communities that require them live in remote locations that are difficult to access. Reliance on a handful of drugs, and a lack of professional expertise in their administration, are thought to be contributing to increased drug resistance in the parasites3. An effective vaccine would help to overcome some of these practical barriers.

Dr Andrew Jackson, a senior author of the study from the University of Liverpool, said: “It was considered impossible to vaccinate against trypanosome parasites because of the sophisticated immune-protective mechanisms they have evolved, so I’m delighted that we have been able to demonstrate that this can be done. Beyond the obvious benefit of a strong vaccine candidate for animal trypanosomiasis, the genome-led vaccine approach we outline in this study is one that could potentially be applied to other trypanosome species and other parasite families.”

The next step will be to validate the results using a cattle model. If successful, work could begin on developing a vaccine for AAT that would be an important tool for tackling poverty in affected regions.

Dr Gavin Wright, a senior author of the study from the Wellcome Sanger Institute and the University of York, said: “This study is an important first step toward relieving the burden of animal African trypanosomiasis (AAT) on both animals and humans in Africa and South America. The protective effect of the vaccine target we identified will first need to be replicated in a cattle model, but I think we can be cautiously optimistic that in a few years’ time we will have made substantial progress against this devastating disease.”

Michael Pearce, AAT Programme Officer at livestock vaccine organisation GALVmed, said: “Trypanosomiasis remains a major disease challenge for livestock and farmers in Asia, Africa and South America, and is a significant human health problem in Africa and South America. Options for control and treatment of trypanosomiasis are very limited and resistance to currently available medicines is an increasing problem. These novel results from the Sanger Institute are a very important and welcome development, opening up the possibility of successful vaccine development for the prevention and control of trypanosomiasis in both humans and animals.”

Notes to Editors:

1 For more details, see the Food and Agriculture Organisation of the United Nations website.

2 For more information on trypanosomiasis in humans, see the WHO website.

3 For more information on attempts to understand, control and prevent AAT, see the University of Glasgow website

The study, published today (27 May 2021) in Molecular Systems Biology, provides important information about how DNA variants can suppress undesirable genetic changes. If confirmed in humans, this biological phenomenon could have an important role in genetic diseases such as cancer or rare developmental disorders, and explain why certain patients suffer from more severe disease than others.

Mutations are changes to the letters of DNA that form the genetic code of multi-cellular organisms. They can be a result of errors when DNA replicates during cell division, or the influence of environmental exposures such as ultraviolet light. While most mutations will have no significant effect on how the cell functions, some can be harmful and lead to genetic diseases such as cancer. Other mutations can be beneficial and contribute to genetic diversity in a species through the natural process of evolution¹.

With six billion letters of DNA in the human genome, the implications of natural genetic variation are vast. As a result, the precise effect of mutations on the function of genes and cells is not fully understood. Mutations that are harmful in one individual may have no negative effect on another. In some cases, this is because the healthy or resilient individuals carry additional mutations, called suppressors, which counteract harmful DNA changes.

In this study, researchers at the University of Toronto screened 1,106 temperature-sensitive alleles2 from 580 essential genes3 in 10 wild yeast strains to see if natural genetic variation would allow the yeast to grow when exposed to an unfavourably high temperature.

They found that 26 per cent of the 580 essential genes could be circumvented by natural variants in at least one wild yeast strain. Yeast colonies that continued to grow were then sequenced at the Wellcome Sanger Institute, in order to search for specific mutations that could be suppressing the temperature-sensitive allele.

Professor Jolanda van Leeuwen, a senior author of the paper from the University of Lausanne, said: “The proportion of harmful mutations in essential genes that could be supressed was unexpected, and because we only sampled a small fraction of wild yeast strains the percentage of mutations that can be suppressed by natural variants is likely to be much higher. The frequency of suppression suggests it could make an important contribution in other contexts as well — including, potentially, for human disease.”

Researchers at the University of Lausanne examined 10 instances of suppression in detail to better understand the suppression effect and how it protected cells. To their surprise, in each case a single mutation was responsible for suppressing the temperature-sensitive allele and enabling cells to live and reproduce.

Dr Leopold Parts, a senior author of the paper from the Wellcome Sanger Institute, said: “In biology, explanations tend to be complex, so it’s unusual to find a single ‘smoking gun’. We might have expected a number of genes to combine to overcome a serious genetic defect like the temperature-sensitive allele, so for this to be the result of a single mutation is very surprising.”

Work is already underway at the Sanger Institute to conduct a similar study in human cells to see how relevant these findings are to the human genome, using commercially available human cell lines from healthy donors. If the same biological phenomenon is at play, it could provide valuable information about how genetic diseases arise and whether ‘rescue mutations’ might one day help clinicians to treat these diseases.

Notes

1 For an overview of genetic mutations, see yourgenome.org

2 An allele is a variant form of the same gene. The combination of alleles influences an individual’s physical traits, such as eye colour. For more information, see yourgenome.org

3 Essential genes are those that are absolutely required for the cell to live and reproduce.

The collaborative study from the University of British Columbia (UBC) and the Strategic Salmon Health Initiative (SSHI) — a partnership between Fisheries and Oceans Canada (DFO), Genome BC and the Pacific Salmon Foundation — traces the origins of PRV to Atlantic salmon farms in Norway and finds that the virus is now almost ubiquitous in salmon farms in B.C.

It also shows that wild Chinook salmon are more likely to be infected with PRV the closer they are to salmon farms, which suggests farms transfer the virus to wild salmon.

Genome sequencing of viruses from farms and wild fish further indicates that transmission occurs between farms and wild salmon.

“Both our genomic and epidemiological methods independently came to the same conclusion, that salmon farms act as a source and amplifier of PRV transmission,” said Dr. Gideon Mordecai, a viral ecologist and Liber Ero fellow with UBC Science and researcher with UBC Medicine, who led the study. “Because separate lines of independent evidence all point to the same answer, we’re confident in our finding.”

Sequencing of 86 PRV genomes helped researchers track the history of PRV emergence in British Columbia. They estimate that the lineage of PRV in the North East Pacific diverged from PRV in the Atlantic Ocean approximately 30 years ago. This suggests that the introduction of PRV to B.C. and infection of wild Pacific salmon is a relatively recent phenomenon, coincident with the growth of salmon aquaculture in the province — not dating back to early attempts to introduce Atlantic salmon to the region, starting in 1874.

“There is much confusion about where PRV is originally from, whether it is transmitted between farmed and wild salmon, and how different lineages of the virus cause different severities of disease,” said Dr. Mordecai. “This study’s genome sequencing clearly indicates PRV is not native to B.C. waters — it originated in the Atlantic Ocean and has been spread around the world through salmon aquaculture.”

The study highlights the role of aquaculture in introducing novel pathogens to new regions, where they then spread to wild fish, and integrates the expertise of the two senior authors, Dr. Kristi Miller, a DFO scientist and Professor Jeffrey Joy, a UBC evolutionary geneticist. It demonstrates the value of genomics in the surveillance of viral pathogens affecting important fisheries resources and how analytical methods derived from the epidemiology of human viruses can be adapted and applied to conserving wild salmon populations.

Further analysis of PRV genomes generated by the study suggested that there has been a growth in the number of PRV infections in B.C. over recent decades. This finding corresponds with the regional growth in salmon aquaculture and high rates of viral infection in salmon farms.

“Our finding that PRV is transmitted between farmed and wild salmon is particularly relevant given recent field and laboratory studies showing the lineage of PRV in B.C. is likely to cause disease in both Pacific and Atlantic salmon” says Dr. Mordecai. A recent Norwegian study found that a Canadian isolate of the virus causes heart lesions in Atlantic salmon. More importantly to the Pacific ecosystem, PRV has been associated with a different disease in Chinook salmon in which blood cells rupture, leading to kidney and liver damage. These are in contrast to the DFO’s assessment that PRV is not a disease agent.

“Our study reaffirms that a more precautionary approach to managing salmon farming in BC is warranted,” says study co-author Dr. Andrew Bateman, of the Pacific Salmon Foundation. “The PRV findings, in particular, support calls to transition from open-net salmon farming towards farming technology that doesn’t allow disease transfer between farmed and wild salmon, protecting BC’s wild Pacific salmon from serious risk in the process.”

“The study provides foundational information necessary to assess the risk of salmon aquaculture on wild fish, as recommended by the Auditor General of Canada’s 2018 Report on Salmon Farming, which criticized DFO’s ability to manage aquaculture in a precautionary manner,” says Professor Jeffrey Hutchings of Dalhousie University, a leading Canadian fisheries scientist who was not involved with the research. “The work by Mordecai, Miller, and colleagues on PRV provides the most compelling, scientifically objective evidence to date that wild salmon in BC are at increased risk of disease because of open net-pen Atlantic salmon aquaculture,” adds Professor Hutchings.