For thousands of years, humanity has had a… complicated relationship with fungus, though at points half-oblivious. On one hand, many cuisines across the world have made use of edible fungi or fermented food and drink for longer than you might expect – the ancient Sumerians liked beer so much, they honored the miracle of fermentation with the patron goddess Ninkasi almost four thousand years ago. On the other hand, fungi have been known culprits in food spoilage across the ages, and even if germ theory didn’t gain traction until the 19th century, that doesn’t change the fact that we have suffered various types of fungal infections since well before that.
This ambivalence still exists in modern time, but the balance is changing as handling processes have been improved and refined. Even if most fungal samples are still infectious, proper handling can prevent contamination, allowing those fungi to be used in a number of ways, from producing antibiotics to many of the cutting-edge biotechnologies being developed today. Last time in our Amazing Samples blog series, we discussed the value in stool. Today, let’s mull over what fungus provides to modern science.
The Birth of Antibiotics
Honestly, no one can write about medical applications of fungus without giving a nod to the discovery of penicillin’s antibiotic properties. Many people have heard the curious story, even if they don’t remember all the details. In 1928, a bacteriology professor at a London hospital, Alexander Fleming, returned from a vacation to discover that one of his petri dishes had been contaminated with mold. Before disposing of the dish, though, he noticed that the mold was encircled by a band free of bacterial growth, and eventually identified that mold as Penicillium notatum. Though he was not initially recognized for the great discovery this was, he began producing a filtered broth that proved a useful disinfectant, and paved the way for further antibiotic development. Read more on this story and the following developments in the ACS’s commemorative booklet.
Penicillin was used from early on against several different bacterial infections, including staphylococcus, streptococcus, and listeria infections. As expected of evolution, though, it did not take long for the bacteria to start fighting back. As early as 1940, penicillin-resistant strains were being observed, most notably due to producing an enzyme to break down the β-lactam ring central to penicillin’s structure. Discovery of that enzyme led to the development of various β-lactamase-resistant forms of the drug, and between that and myriad other responses to adapting bacteria, the market now has many different forms and derivatives of penicillin still being used for various illnesses. Additionally, the romanticized nature of penicillin’s discovery helps to remind us that even “bad” samples or data might sometimes be put to good use.
Yeast Manufacturing Biologics
Most microbiologists have dealt with yeast at some point or another, as being single-celled, they are an easily-produced model to work with and observe the basic processes of eukaryotic cells. Additionally, while humans already love yeast for its knack for fermentation, that ability has also been repurposed for more practical uses, such as for fuel ethanol.
Yeast can make some things far more interesting than just ethanol, however. Even if it doesn’t match the popularity of bacteria or Chinese hamster ovary cells, yeast still accounts for an appreciable number of biologics. Only a few years ago, there were over 20 yeast-produced recombinant protein therapies in US/EU markets, 15% of the total at the time. This is primarily due to yeast and other fungi occupying an odd middle-ground as a protein expression system. They have the upper hand over bacteria through their ability to glycosylate the proteins they produce, but are limited to only simple glycoproteins due to immunogenicity issues in humans. Per the link above, it's evident that yeast is significantly more cost-effective than the more consistently immune-friendly mammalian cells, which could mean that yeast will hold its ground in the biosimilar production sphere for the time being.
Cleaning the Environment
You might remember hearing about a 2007 oil spill in San Francisco, but did you know part of the cleanup effort used mushrooms? A volunteer force was mobilized with an odd pair of cleanup tools – hair mats and oyster mushrooms. Due to hair’s structure, which we discussed in a previous post, woven mats of hair were used to wick oil from water, and the oyster mushrooms were used to digest the oil-soaked mats into non-toxic soil.
This is just one example of mycoremediation, or fungal bioremediation. Essentially, the fungi used for bioremediation have extremely effective digestive capabilities, able to degrade a broad range of organic molecules generally thought to be intractable or pernicious. The hydrocarbons found in crude oil can easily be broken down, though some substrate like hair, straw, or sawdust is generally required as a base for the fungal growth. Additionally, this practice isn't limited to oil; even pollutants like heavy metals or radioactive compounds can be treated with mycoremediation. The fungus can draw such components from the soil and then be physically removed and disposed of in a more environmentally responsible manner. Read more about mycoremediation here.
As you can see from the references above, fungus has had an enormous impact on science and continues to shape the biotech industry. From the development of antibiotics to mitigating the impact of environmental disasters, it is no wonder that fungus is an Amazing Sample. Do you work with fungus samples? Tell us about it in the comments below! To learn more about managing the storage of high-value biologics, download our eBook Defense in Depth: Off-Site Storage of Biological Specimens and Biopharmaceuticals Risk Mitigation.