Finding New Antibiotics: Nature’s Guide for Dummies | Sarah Worsley
With the seemingly unstoppable rise in pathogen resistance and dire warnings of a pre-antibiotic era looming, there has never been a better time to be thinking seriously about revamping our stocks of antimicrobial drugs. But where does one go when in need of a new antibiotic?
Probing the Soil
Surprisingly, many of the antibiotics that we use today, such as Streptomycin, were originally isolated from the soil environment. Here, bacteria and fungi make antibiotics as a form of chemical warfare, enabling them to eliminate other species and dominate the use of resources such as nutrients and living space. We isolated these compounds and put them to work against pathogens in the clinic.
Surely an obvious suggestion then, now that we need a fresh wave of antibiotics, would be to pick up our spades and go digging for new compounds.
Unfortunately, as scientists have spent more and more of their time rummaging in the dirt, the same antibiotic molecules have been continuously rediscovered with few new ones being identified. Instead much of the attention over the past few decades has been on the chemical synthesis of new antibiotics in the laboratory. However, as quickly as these have been developed, pathogens have evolved fancier ways to evade them. Welcome to the biological arms race…
Luckily nature is, again, here to help. It turns out that many species do a much better job at finding useful, antibiotic-producing bacteria than we do.
Almost all organisms, at some point during their lifecycle, interact extensively with microorganisms from their environment, forming what is known as a microbiome. In organisms as different as sponges, birds and plants, many of these microbes are specifically selected because of the protective benefits that they lend to their host. To give one example, the Hoopoe bird has been found to accumulate antibiotic-producing Enterobacteria in their preen glands, which are then spread over the feathers to help reduce the growth of feather-degrading pathogens.
So if we want to find some new antibiotics, microbiomes may well be the next port of call. One advantage of looking here is that, rather than the problem of rediscovery emerging from soils, many of the natural products uncovered from microbiomes are likely to have novel activities due to the bacteria have specifically coevolved with the host. Thus they continue to produce effective antibiotics in return for rewards from their host, such as nutrients.
As well as making direct use of this new source of antibiotics there is also the potential to learn from the mechanisms by which host organisms recruit these beneficial bacteria in the first place.
This is the focus of my work on leafcutter ants.
These ants, despite human ingenuity being allegedly unmatched, have been farming for over 50 million years. They cultivate the fungus Leucogaricus gonglyphorous for food, using cut-up leaves as compost. Like our own food crops however, the fungus is constantly under threat from invading pathogens, hence why the ants have recruited several species of antibiotic-producing Actinobacteria which live on the ants cuticle and help to keep the fungal gardens clean. Pretty clever right?
My lab is working to characterise many of these antibiotics as well as switch on the production of those that the bacteria can make, but only under certain conditions. It is my job, however, to work out how the ants get hold of these useful symbionts in the first place. Since the bacteria are found to cluster around glands on the ants surface it is though that nutrients are likely to be involved. My experiments will aim to test this by tracing a radioactive label from the ant’s food source to the bacteria. If you’re really interested you can check out the live feed of our ant colony from the John Innes Centre.
Understanding the construction and maintenance of this protective community could have huge ramifications, not only for the way that we search for new natural products ourselves but also for manipulating other microbiomes to increase the representation of good, protective bacteria. This could be in systems as such as crop plants, or microbial communities found within the human gut.
It is hard to believe that organisms as small and pesky as ants may be this important, but, in fact, ants may be key players in what is emerging to be one of the largest medical challenges faced by human society today.