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From soil microbe to saviour of humanity – How Streptomyces (could) save the world | Sam Prudence

Why do I do what I do? Well firstly, what do I do?

My PhD is in molecular microbiology, which means I study the molecular fundamentals of microbes - the nuts and bolts of microscopic life. Think of me as like a mechanic for cells, except I don’t really know how the engine works, so I just break random bits to see what happens. Specifically, I look at a type of bacteria called Streptomyces, they are weird (for bacteria) because, unlike most, they grow in long chains of cells (Figure 1) called mycelia, these spread throughout the soil (where the bacteria live) and feed off decomposing matter (called detritus). They are famed (amongst microbiologists at least) for being prolific producers of antibiotics. In order to reproduce, a colony of Streptomyces must produce spores which can then disperse, allowing the bacteria to colonise new areas (Figure 2). At this stage in their life cycle (sporulation) they begin to make antibiotics as a chemical weapon to defend the colony from invading microbes, competing for that nutritious detritus (see a colony of Streptomyces coelicolor producing a blue antibiotic in figure 3).

Figure 1: Electron microscope image of Streptomyces cinnamoneous growing in filamentous chains of cells. Image reproduced from Finlay et al. (Norwich Research Park image library).

Figure 2: Diagram showing the Streptomyces life cycle. Beginning with spore germination the colony spreads, feeding off of decomposing organic matter in the soil. After this aerial hyphae form and spore production (sporulation) begins. At this stage the bacterial colony produces antibiotics as a self-defence. Image reproduced from Seipke et al. (2012).

Figure 3: Image 3. Microscope image of Streptomyces colonies producing a blue pigmented antibiotic called actinorhodin. Image reproduced from Hosskison et al. (Norwich research park image library).

About two thirds of all clinical antibiotics, the ones your doctor may have given you for a bacterial infection, were originally made by Streptomyces. Scientist’s figured out what the antibiotic compounds Streptomyces make are, then copied them for use as medicine. In our lab, we study Streptomyces found living in all sorts of interesting places like leafcutter ant nests, plant roots and even the back garden of 10 Downing Street! My colleagues are trying to find any new antibiotics Streptomyces might be producing to combat drug resistant infections (reason number one Streptomyces (could) save the world). If you want to learn more about this work a great place to start is the 'Superbugs exhibition' in the Science museum, displaying some of my colleagues work until November 2019.

But what do I actually do?

I study how Streptomyces interact with the community of microbes that live in and around plant roots, we call this community the root-associated microbiome. Here we have Streptomyces bacteria, talented producers of antibiotics (killers of disease causing bacteria and fungi) living inside and around the roots of plants! This includes loads of important crops like wheat, corn, barley, potatoes, rice and tea plants (yes like PG tips/Yorkshire tea-tea plants). If I can figure out the role of Streptomyces within this community we may be able to develop techniques for harnessing their antibiotic abilities to protect our crops from disease.

Figure 4: A tea plantation, home to Streptomyces sp. XY006, discovered in 2017

But what’s the big deal? We have loads of crops, right?

Unfortunately, no, the global population is set to rise to over 9 Billion by 2050; as we progress (thankfully), living conditions are starting to improve and poverty is decreasing in developing nations. This means the global demand for food is about to rise significantly. Everyone being alive is a pretty good problem to have, but we still need to find ways to feed everyone. As of 2015 around 10% of the global population are going hungry, 780 million people! We are about to have 2 Billion more mouths to feed, and climate change is causing sea levels to rise, reducing the amount of land available for farming. Over the next few decades we have a big challenge…. grow more food using less land.

Figure 5: Map showing the global prevalence of undernourishment, reproduced from the United Nations Food and Agriculture Organisation (2015).

It might sound impossible but I believe if we can increase our crop yields, whilst decreasing the amount of our crops getting destroyed by pests and diseases, we can succeed.

Conventional methods of pest control use chemical pesticides which severely damage ecosystems, pests can also develop resistance (much like the antibiotic resistant bacteria) rendering them useless. If we could harness the abilities of Streptomyces in the root-associated microbiome to protect crops from disease, a biocontrol agent, then we can keep our crops protected without harming the environment, way number 2 Streptomyces (could) save the world!

So how exactly DO we go about deciphering what Streptomyces does within the community – in particular how they are fighting competing bacteria?

We start by looking Streptomyces genetic code which contains around 8000 genes. With 8000 genes, there is a lot Streptomyces can do; they code for everything from normal stuff like protease enzymes (they break down proteins, it’s basically how they chew their food), to cool stuff like the biosynthetic enzymes which make antibiotics. I am interested in the genes which code for something called a type seven secretion system, a system used by cells to transport proteins from the inside, out. It is a pore which sits in the cells membrane (like its skin) and it allows specific proteins to pass through to the outside of the cell but not others. Only proteins with specific features (we call these motifs) are allowed through, so if it hasn’t got the right motif, it’s not getting through. Many bacteria possess this system, for example Staphylococcus aureus (you may have heard of MRSA?) use it to secrete toxins which kill competing bacteria (actual toxic proteins, not the imaginary things that the internet tells you are in baked beans). My hypothesis is that, like MRSA, Streptomyces use this system to kill competing bacteria within the root associated microbiomes. If this turns out to be true it could indicate that Streptomyces are what we call a keystone species within the community, meaning their presence helps to determine which other bacteria are living in that environment.

So how will I investigate this?

Well, remember how I said I’m like a bad mechanic that breaks things? That is exactly how I will test how important type seven secretion is for competition (or to secrete those toxic proteins that kill off Streptomyces closest competitors for that oh so nutritious decomposing material). Using genome editing I will break the secretion system, then we will observe what happens!

You may have heard about CRISPR Cas9 in the news, a revolutionary new genome editing system which may help eradicate genetic diseases like Huntington disease and Cystic Fibrosis. CRISPR allows you to make specific changes to a DNA sequence (hence the potential as a medicine) and I am using this to make specific changes to the genes for type seven secretion. This enables me to produce strains of Streptomyces which cannot make a functioning type 7 secretion system (so essentially I’ve broken it), we call this a mutant strain. Then we can then see how well this mutant strain can compete with other bacteria in and around plant roots in comparison to unchanged Streptomyces (the wild-type), which can still use the secretion system. If type seven secretion is in fact being used to eradicate the competition we would expect our mutant strain to perform worse than the wild type. Figuring out what this secretion system does is the first step towards being able to wield the awesome potential of Streptomyces to protect crops from disease, (maybe) saving the world!

In short, I do what I do because globally food security has serious impending challenges with increasing populations, compounded by climate change. Streptomyces bacteria and the microbiomes within which they live contain a plethora of biological capabilities and curiosities; if we understand those we may be able to use them to help us grow more food, and to do so in a more environmentally friendly way – this is how Streptomyces (could) save the world!



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