Analysis of genes linked to disease shows likelihood of superbugs arising is far greater than feared

Lab discoveries of single mutations that increase infectiousness have quadrupled since 2015

Far more bacteria 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 microbes.

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 fruit, 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.