6 Innovative Applications of Microbes

Whilst many people associate microbes with being bad and causing illness and disease, they also have many beneficial properties and can inhabit some of the most inhospitable corners of the globe. For many years now, humans, animals and plants have exploited the properties of microbes for their own benefit. Here we discuss some of the many and varied uses to which microbes are being applied.

Combating agricultural pests

Whilst pesticides have done a great job at killing off undesirable insect pests that plague our crops, many are indiscriminate, killing beneficial pollinators too. They also cause problems when run-off from fields ends up in our waterways, damaging the delicate ecosystems that live there. Long-term use means that inevitably, resistant populations are selected for and over time the pesticides fail to protect crops. Consequently, attention has increasingly turned to alternative approaches.

One such example exploits the symbiotic relationship between the western flower thrip and the bacterium Pantoea.¹ The thrip feeds on a wide range of crop plants and transmits topoviruses which are pathogenic to a range of crop species. Scientist have engineered a strain of Pantoea to constantly produce dsRNA from its home in the insect’s gut. These interfering RNAs (iRNAs) target a gene essential to the thrip’s survival resulting in host mRNA degradation and insect death.

The technology termed symbiont-mediated RNAi (SMR) is still in its developmental stages but offers a high degree of target species specificity. Unlike engineering the crops themselves to reduce susceptibility to pests, this approach also has the advantage of protecting all the crop species that are targeted by that particular pest.

The secret ingredient is microbes!

Microbes are involved in the production of many foods, like bread, cheese and sauerkraut, and some that are almost entirely the microorganisms themselves, like yeast extract or mycoprotein meat alternatives. However, microbes also have great power to alter the flavors in foods. Each microorganism produces characteristic metabolites which will depend on the nutrients available to them. These may in turn be metabolized into yet more products by other microbes present so it is important to have the right balance of microbes to get the desired flavors. In industrial food production, this is often achieved using starter cultures to introduce a balance of desirable microbes and ensure consistency in the final product. The cheese industry provides an excellent example of the importance of balancing microbes. Bitter notes can come from the breakdown of casein in the milk to hydrophobic amino acids, whilst sour tastes may come from the breakdown of sugars for example. The characteristic “cheesy” odor has been associated with the yeast Yarrowia lipolytica which turns tributyrin into butanoic acid, and Penicillium roqueforti imparts “blue” notes. Too much or too little of any particular flavor can make the product unpalatable. Microbes are even vital for producing the characteristic holes in Swiss cheese which develop as a result of the fermentation of lactate to propionate, acetate, CO₂ and H₂O by Propionibacterium freudenreichii.²

Let them eat waste

Radioactive materials have provided us with the benefits of energy generation, medical treatments and defenses. However, they have also left us with a problem – safe disposal. Whilst the half-life of some radioactive materials is short, others such as uranium, may remain hazardous to life for decades. One answer that has been widely employed is to simply store the waste in silos or bury the problem underground. One concern with burying radioactive waste underground until it is safe has been the leaching of radioactive molecules into the surrounding soil and rock as elements like uranium become mobile when they form soluble complexes with some organic molecules. However, bacteria could come to the rescue. Scientists have found that some bacteria are able to use radionuclides, such as uranium and neptunium, in place of oxygen and in the process make them insoluble.³

Treatment of the repositories with radioactive molecule-munching microbes could slow down the movement of radioactive molecules and therefore prevent or reduce their movement into the surrounding area during the radioactive breakdown process. The approach has also been suggested as a treatment for contaminated soil.

Making and breaking plastic

In a time of global concern over the negative impact of plastic pollution, the discovery of “plastic-eating bacteria” sent ripples of excitement through the scientific community. In 2016, a naturally occurring bacterial strain, named Ideonella sakaiensis 201-F6, was discovered in a waste dump in Japan that was able to degrade plastic, including the notoriously hard to crack polyethylene terephthalate, also known as PET, and use it as a food source.⁴ Since then, scientists have been working to reveal the detailed structure of the PETase enzyme that conveyed this property. The structure appeared very similar to an enzyme used by bacteria to break down the protective cutin polymer that coats some plants.

By a stroke of good fortune, the group of researchers investigating the PETase inadvertently engineered an enzyme that is even better at degrading the plastic than the one that evolved in nature.⁵ They found that the enzyme can also break down other forms of plastic, opening doors to sustainably recycling many plastics in the future that are currently challenging.

Treating illnesses with viruses

There are many diseases that have their basis in genetics – such as cystic fibrosis and severe combined immunodeficiency (SCID). The mission to try and “fix” these genetic problems through the use of gene therapy started in the 1970s. The idea was to replace the faulty copy with a good copy or otherwise inactivate a faulty gene, but researchers needed a means to interact with the problematic gene. This is where microbes came in. By their very nature, viruses are able to attach to and enter cells and, once inside, interact with the host genome, normally to facilitate their own replication. However, researchers have been able to hijack this property for their own means.

Currently, there are three main groups of viruses (adenoviruses, adeno-associated viruses and retroviruses/lentiviruses) that form the backbone of gene therapy studies. Initially, trials were plagued by issues with genotoxicity and immune responses, but decades of research have enabled many of these problems to be ironed out. Treatments using gene therapy techniques are now available for SCID, cancer and blindness following the approval in the EU of the first gene therapy, Glybera for acute pancreatitis, in 2012. With over 2,300 clinical trials conducted already, it is only a matter of time before more treatments follow.

One major hurdle that must be overcome if gene therapy is to succeed as a therapeutic treatment is the ability to scale up production, as techniques for viral vector production and purification suited to a research setting are not compatible with large-scale production.

Van Gogh, Monet, Da Vinci and E. coli?!

Scientists have recreated an image of Leonardo da Vinci's Mona Lisa from approximately one million Escherichia coli (E.coli) of all things!⁶ E. coli are fantastic swimmers and can move ten times their length per second. Ordinarily, the bugs process oxygen to fuel their movement. However, the protein proteorhodopsin was identified in ocean-dwelling bacteria, where it enabled bacteria to fuel themselves using light. By engineering a strain of E. coli to produce this protein, scientists managed to create bacteria, the movement of which could be controlled remotely using light. They projected light onto a layer of cells uniformly for five minutes before introducing a negative image of the Mona Lisa. After a further four minutes, the engineered bacteria had concentrated in the dark areas of the space forming a recognizable image. To refine blurring, a feedback control loop, where the bacterial shape is compared to the target image every 20 seconds and the light pattern updated accordingly, was employed resulting in a near perfect replica.

Aside from creating artwork, the ability to control the activity of swimming bacteria with light opens up potential applications for light-controllable active materials or even to surround and transport larger objects.

References

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4. Yoshida S, Hiraga K, Takehana T, et al. A bacterium that degrades and assimilates poly(ethylene terephthalate). Science. 2016;351(6278):1196-1199. doi: 10.1126/science.aad6359.

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