GENE DATA SUGGESTS 'SUPERBUG' THREAT IS UNDERESTIMATED
Discoveries of single mutations that increase microbe infectiousness have quadrupled since 2015
Far more microbes are one step away from becoming dangerous than previously thought, say the team managing the world’s only specialist database on the disease-causing genes of microorganisms.
The scientists, led from Rothamsted Research, say there has been a sharp rise in the number of laboratory studies that show how just a single mutation can create highly infectious or ‘hypervirulent’ strains of disease-causing bacteria, fungi and water moulds.
These include the microbes responsible for human diseases such as TB and salmonellosis, as well as economically important crop diseases of fruits, vegetables and cereals.
Writing in the journal Nucleic Acids Research, the team report that the number of such hypervirulence genes that have been found has risen from 112 in 2015, to the current total of 475.
Hypervirulence now accounts for almost 5% of all database entries and is particularly prevalent amongst bacteria.
When a single gene is so pivotal, then it is much more likely that a hypervirulence mutation will occur, potentially affecting both man-made and environmental systems - from food chains and hospitals to the health of our farmed and natural ecosystems.
As well as human diseases, the database also covers infections in mammals, plants, fish and insects – the majority of which we depend on for food, or the proper functioning of ecosystems.
Plant pathologist and geneticist Dr Kim Hammond-Kosack, who oversees the database, said: “The increasing number of hypervirulent interactions indicates that scientists have identified many new factors occurring during infection. These genes need close monitoring if we are to halt the emergence and spread of severe disease outbreaks.”
Infectious diseases are a consequence of the battles played out between the molecules produced by disease-causing organisms such as bacteria, fungi and water moulds - which allow them to overcome or evade host immune systems - and the host’s own molecular defences, such as antibodies.
It is the underlying genes responsible for shaping these interactions and their impact on disease symptoms that are recorded in the Pathogen-Host Interaction database (PHI-base), along with a measure of their ability to infect and harm their host, or conversely, repel and protect against the invader.
The increase in hypervirulence genes being discovered is partly down to genetic testing being faster and cheaper than ever before, allowing scientists to study more genes and more diseases in even greater detail.
But along with their colleagues in Cambridge, UK and Bangalore, India, the Rothamsted team also blame the increasing effects of climate change, human migration, and the global trade of fresh goods on the rise of disease problems.
Dr Hammond-Kosack said: “In addition, we have the emergence of many new disease causing organisms, we have diseases jumping species barriers into new hosts, and we have a growing resistance to antibiotics and pesticides –– coupled with a rise in legislation banning or restricting many existing chemicals we use for control –– all of which means microbial infections are of ever growing concern to human, animal and plant welfare.”
In the United Kingdom alone, the total economic burden from infectious diseases is estimated at £30 billion annually, and accounts for 7% of all deaths.
Single mutations in globally important human pathogens could create more infectious strains of disease-causing microbes, such as the bacteria Salmonella enterica, Mycobacterium tuberculosis, and Staphylococcus aureus, as well as the fungi Aspergillus fumigatus and Candida albicans.
Threats to our food system come from bacteria such as Erwinia amylovora, which causes fire blight disease on different orchard trees; Xylella fastidiosa, which kills olives trees; Xanthomonas oryzae, which infects rice crops; the fungi Verticillium dahlia, which cause vascular wilt disease in many horticultural crops; and Botrytis cinerea, which causes grey mould disease on numerous fruits and vegetables both pre- and post-harvest - whilst the water mould Phytophthora infestans, devastates potato crops and was the primary cause of the Irish Potato Famine in the 1840s.
Increasing concerns over the rise and spread of economically important crop diseases led to Dr Hammond-Kosack being invited to UNESCO headquarters in September to speak about PHI-base to representatives from all the European plant-protection agencies within the European and Mediterranean Plant Protection Organization (EPPO).
The UN have designated 2020 as the International Year of Plant Health, to raise global awareness on how protecting plant health can help end hunger, reduce poverty, protect the environment, and boost economic development.
The Pathogen-Host Interactions database (PHI-base) available at www.PHI-base.org is funded by the Biotechnology and Biological Sciences Research Council (BBSRC) – part of UK Research and Innovation (UKRI) – and is being developed and maintained by scientists at Rothamsted Research.
The database contains molecular and biological information gathered from published studies into genes found to affect disease progression in humans, plants and animals. Viruses are not included, due to their extensive coverage in other databases.
PHI-base also curates literature describing specific gene alterations that have no impact on disease, in order to provide complete datasets for comparative purposes.
PHI-base version 4.8 (September 2019) contains 3454 manually curated references, and provides information on 6780 genes from 268 pathogens, tested on 210 hosts in 13,801 interactions.
Host species consist of approximately 60% plants (split 50:50 between cereal and non-cereal plants), and 40% other species of medical and/or environmental importance.
All the data in PHI-base can be freely downloaded, so that scientists can carry out comparative analyses to identify both the species-specific requirements and the generic requirements underpinning a microbe’s ability to cause disease.
About Rothamsted Research
Rothamsted Research is the longest-running agricultural research institute in the world. We work from gene to field with a proud history of ground-breaking discoveries, from crop treatment to crop protection, from statistical interpretation to soils management. Our founders, in 1843, were the pioneers of modern agriculture, and we are known for our imaginative science and our collaborative influence on fresh thinking and farming practices.
Through independent science and innovation, we make significant contributions to improving agri-food systems in the UK and internationally. In terms of the institute’s economic contribution, the cumulative impact of our work in the UK was calculated to exceed £3000 million a year in 20151. Our strength lies in our systems approach, which combines science and strategic research, interdisciplinary teams and partnerships.
Rothamsted is also home to three unique resources. These National Capabilities are open to researchers from all over the world: The Long-Term Experiments, Rothamsted Insect Survey and the North Wyke Farm Platform.
We are strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), with additional support from other national and international funding streams, and from industry. We are also supported by the Lawes Agricultural Trust (LAT).
For more information, visit https://www.rothamsted.ac.uk/; Twitter @Rothamsted
1Rothamsted Research and the Value of Excellence: A synthesis of the available evidence, by Séan Rickard (Oct 2015)
The Biotechnology and Biological Sciences Research Council is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government.
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The Lawes Agricultural Trust, established in 1889 by Sir John Bennet Lawes, supports Rothamsted Research’s national and international agricultural science through the provision of land, facilities and funding. LAT, a charitable trust, owns the estates at Harpenden and Broom's Barn, including many of the buildings used by Rothamsted Research. LAT provides an annual research grant to the Director, accommodation for nearly 200 people, and support for fellowships for young scientists from developing countries. LAT also makes capital grants to help modernise facilities at Rothamsted, or invests in new buildings.