A piece of cheese is a perfect playground for fungal antibiotics.

Behold the microscopic power of cheese. The dairy product has been a staple food for generations, but it’s also helping microbiologists better understand nature’s microbiomes. In a study published May 10 in the journal mBioa team of researchers used cheese rinds to demonstrate how fungal antibiotics can influence the development of microbiomes.

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The metabolites produced by fungi can improve human health. Some secrete penicillin, which is then purified and used as an antibiotic. For this study, the scientists set out to better understand how fungi interact with the microbes that live alongside them in microbial communities, with a particular focus on the relationship between fungi and bacteria.

“My lab is interested in how fungi shape the diversity of microbial communities where they live. Fungi are widespread in many microbial ecosystems, from soils to our own bodies, but we know much less about their diversity and roles in microbiomes compared to the more well-studied bacteria,” said co-author and Tufts University microbiologist, Benjamin Wolfe, in a statement. “To study the ecology of fungi and their interactions with bacteria, we used cheese rinds as a model microbial ecosystem to understand these basic biological questions.

The cheese rinds themselves are microbial communities that form on the surface of naturally aged cheeses such as brie, taleggio, and some types of cheddar. As cheeses age, fuzzy and sometimes sticky layers of microbes form on the surfaces of the cheese. Microbes slowly break down as the cheeses curdle and grow on the surface to create the aromas and colors that give cheese in the fancy part of the grocery store its most unique properties.

Wolfe and his team began by investigating the problem of moldy cheese spreading across the surface of cheeses and disrupting the normal development of the rind. This makes it look like the cheese rinds are disappearing as mold invaded your cheese cave. They collaborated with microbiologist Nancy Keller’s lab at the University of Wisconsin to find out what this mold was doing to the shell microbes and what chemicals the shell-disrupting mold may be producing.

First, the researchers deleted a gene (laeA) in the Penicillium mold that can control the expression of chemicals that fungi can secrete into their environment. These compounds are called specialized or secondary metabolites.

“We know that many fungi can produce metabolites that are antibiotics because we have used them as medicines for humans, but we know surprisingly little about how fungal antibiotics work in nature,” Wolfe said. “Do fungi really use these compounds to kill other microbes? How do these antibiotics produced by fungi affect the development of bacterial communities? We add our normal and our laeA-erased Penicillium to a community of cheese rind bacteria to see if removing laeA caused changes in the way the community of bacteria developed.”

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When laeA was removed, most of the antibacterial activity of the Penicillium the mold was lost. This discovery helped the team narrow down specific regions of the fungal genome that could produce antibacterial compounds. They narrowed it down to a class of compounds called pseudotins. The metabolites are produced by multiple types of fungi and can modulate the immune system, kill insects, and inhibit bacteria.

The study showed that pseudotins can also control how bacterial communities living with that fungus grow and develop. Pseudotins are strongly antibacterial, meaning they inhibit some of the bacteria found in artisan cheeses, including staphylococcus, brevibacterium, brachybacteriumand psychobacter. This process caused a change in the microbiome composition of the cheese rind.

It also shows that antibiotics secreted by fungi can control how microbiomes develop, as the metabolites are found in other ecosystems, including the human microbiome and soil ecosystems. The team expects that these mechanisms of interactions between fungi and bacteria are widespread.

“Our results suggest that some species of nuisance molds in artisan cheeses may disrupt normal cheese development through antibiotic deployment,” Wolfe said. “These findings allow us to work with cheesemakers to identify which molds are the bad guys and how to manage them in their cheese caves. It also helps us appreciate that every time we eat artisan cheese, we are consuming the metabolites that microbes use to compete and cooperate in communities.”

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