Resistance to known antibiotics is one of the greatest concerns of 21st-century medicine, but finding new ones is proving difficult. Now scientists in the EU believe the answer may lie with insects such as ants.
There are tens of thousands of known species of ant. One of the most evolved groups is the leafcutters, so called because they march up trees, snip away at leaves and bring the pieces back underground to the colony, where they are fed to a fungus.
The fungus grows and creates food for the ants. In essence, then, the ants are farming – and they have been doing it for millions of years longer than humans have.
Leafcutters have to control pests on their crop, just like humans do. In fact, their bodies nurture bacteria, which generate antibiotic ‘weed killers’ to protect the fungus – and themselves – from infection.
When microbiologist Dr Matthew Hutchings at the University of East Anglia (UEA) in Norwich, UK, found out that leafcutters hosted bacteria, he wanted to find out which ones. ‘I thought maybe they are making antibiotics we’ve never seen before, that we could use in medicine,’ he said.
Last year, Dr Hutchings, along with Dr Hong Gao, funded by the EU's Marie Skłodowska-Curie actions, and colleagues identified a series of antibiotics generated by bacteria on the ant Allomerus – not a leafcutter itself, but another fungus farmer.
Those antibiotics were variations on ones already known in medicine, but Dr Hutchings believes they are just the tip of the iceberg.
There is a lot hanging on work like this: no new classes of antibiotics have been discovered for 25 years, and some bacteria are already proving very difficult to treat with what is currently available.
As Dr Hutchings identifies more ant-based antibiotics in his lab, he is also working with another Marie Skłodowska-Curie Fellow, Dr Tabitha Innocent at the University of Copenhagen in Denmark, to understand why only certain bacteria grow on ants.
What Dr Innocent finds interesting is that the cocktail, or ‘microbiome’, of bacteria hosted by the ants becomes more complex in the older leafcutters. Since it is only the mature ants that go to collect leaves, she believes the complexity may serve to protect the ants from the variety of different pathogens found outside the colony.
‘The microbiome could have benefits that we don’t yet understand’
Dr Tabitha Innocent, University of Copenhagen, Denmark
‘It certainly seems to be the case that the microbiome of older ants that emerges is beneficial, and could have benefits that we don’t yet understand,’ she said.
But how do ants assemble one particular microbiome of bacteria over another? To answer this question, mathematical modellers at UEA are forming predictions of how bacteria compete with each other on the ant’s body, and how the ant can influence this competition by, for instance, secreting food.
Dr Innocent can then test these predictions by replicating the conditions of the competition in the lab.
The work could help scientists to understand why certain combinations of antibiotics are better than others at treating infections. It could also allow scientists to develop crops for humans that naturally harbour protective bacteria on their roots, thereby avoiding the need for fungicides.
But, perhaps the solution to the problem of antibiotic resistance does not lie in traditional antibiotics, after all. Professor Jens Rolff at the Freie Universität Berlin in Germany believes there is merit in a different type of antibiotic – proteins known as antimicrobial peptides – which are used for defence mostly by larger organisms, including humans.
He believes that it may be the use of a mixture of these proteins, rather than a single agent, that has made insects so effective at repelling disease. ‘There is no golden bullet,’ he said.
Since 2010, Prof. Rolff has been backed by the EU’s European Research Council to investigate antimicrobial peptides, using the beetle Tenebrio molitor as a model organism.
Last year, he found that bacteria killed by some of these proteins do not activate ‘stress pathways’, which are what ultimately cause them to mutate, or evolve, to become antibiotic-resistant. ‘Basically, bacteria killed by antimicrobial peptides die peacefully,’ said Prof. Rolff.
The finding suggests that if antimicrobial peptides were used for antibiotics in humans rather than those originating in bacteria, they might be effective for a lot longer. It might also suggest that it is no coincidence that human bodies naturally contain these proteins.
‘Multicellular life uses antimicrobial peptides, and I think one reason might be that it is not in their interest to fuel evolution of pathogens,’ said Prof. Rolff.
Drug-resistant bacteria cause around 25 000 deaths each year and over EUR 1.5 billion in healthcare costs, according to EU statistics.
Under its 2011 action plan against antimicrobial resistance, the EU has identified seven areas where measures are most necessary.
These include ensuring that antimicrobials are used appropriately in both humans and animals, and developing new effective antimicrobials or alternative treatments.
Researchers haven’t discovered a new class of antibiotics since the late 1980s. However, one of the goals of the Innovative Medicines Initiative, a EUR 3.3 billion partnership between the EU and drug developers, is to create at least two new therapies for antimicrobial resistance or Alzheimer’s disease.
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