Newswise — Washington, DC – Fungi generate substances that humans have utilized for health enhancement. One instance is the excretion of penicillin, which is later refined and employed as an antibiotic, thereby paving the way for the emergence of numerous other antibiotics. Nevertheless, the comprehension of the ecological impact of fungal metabolites on microbial communities remains limited. Recently, scientists employed cheese rinds to showcase how fungal antibiotics can affect microbiome development. The publication of this study can be found in mBio, an open-access journal of the American Society for Microbiology.

Benjamin Wolfe, PhD, who is an associate professor in the Department of Biology at Tufts University and the lead researcher of the new study, stated that his team is exploring the manner in which fungi influence the variety of microbial communities in their habitat. While fungi are present in numerous microbial ecosystems, such as in soils and our bodies, their diversity and roles in microbiomes have been less investigated compared to bacteria, which have been widely studied. Wolfe's lab concentrates on examining how fungi interact with other microorganisms in microbial communities, with an emphasis on fungal-bacterial interactions. "We employ cheese rinds as a model microbial ecosystem to comprehend the fundamental biological inquiries of fungi and their interactions with bacteria," said Wolfe, describing the team's approach to studying the ecology of fungi.

The surfaces of certain naturally aged cheeses, such as Brie, Taleggio, and certain Cheddars, give rise to microbial communities known as cheese rinds. These fuzzy and occasionally tacky layers are collections of microorganisms that thrive as the cheese matures. They gradually break down the cheese curd while expanding on the surface and creating scents and pigments that provide each artisanal cheese with distinct qualities.

A few years ago, a cheesemaker contacted Wolfe, seeking assistance with a mold issue. The cheesemaker's cheeses were experiencing a surge of mold growth on their surfaces, which was interfering with the typical formation of their rind. The mold seemed to be invading their cheese aging area, causing the rinds to vanish. This invasion of mold provided an excellent occasion for Wolfe and his team to explore the ecology, genetics, and chemistry of fungal-bacterial interactions.

To determine how this mold was affecting the microbial community of the rind, Wolfe's team partnered with Nancy Keller's laboratory at the University of Wisconsin. They sought to investigate the mold's impact on the rind microorganisms, as well as the chemicals that the mold could be generating, which may interfere with the rind's development.

To conduct their research, the scientists initially eliminated a gene called laeA in the Penicillium mold. This gene regulates the production of specialized or secondary metabolites, which are chemicals that fungi can emit into their surroundings. "We are aware that numerous fungi can generate metabolites that have antibiotic properties because we have used them as medicines for humans. However, we have relatively limited knowledge of how these fungal antibiotics function in nature," explained Dr. Wolfe. "Do fungi utilize these substances to eradicate other microorganisms? How do these antibiotics produced by fungi influence the growth of bacterial communities? We introduced both our normal and laeA-deleted Penicillium into a population of cheese rind bacteria to determine if deleting the laeA gene altered the development of the bacterial community."

The scientists discovered that removing the laeA gene caused a significant decrease in the antibacterial activity of the Penicillium mold. This was a significant breakthrough because it enabled the researchers to identify precise regions of the fungal genome that might be responsible for generating the antibacterial compounds. Eventually, they were able to narrow it down to a single class of compounds known as pseurotins. These metabolites are produced by various fungi and have been found to have noteworthy biological properties, such as modulation of the immune system, insecticide properties, and inhibition of bacterial growth.

This research marks the initial study that demonstrates that pseurotins can influence the growth and development of bacterial communities coexisting with fungi. The pseurotins generated by the Penicillium mold in cheese are highly effective against bacteria and notably hindered the growth of certain types of bacteria more than others, such as Staphylococcus, Brevibacterium, Brachybacterium, and Psychrobacter, which are commonly present on artisanal cheeses. As a result, the presence of the Penicillium-produced pseurotins induced a significant alteration in the composition of the cheese rind microbiome.

The research provides evidence that fungal-produced antibiotics have the capacity to regulate the development of microbiomes. Given that various fungi can produce comparable metabolites in diverse environments, such as soil ecosystems and the human microbiome, the researchers believe that these mechanisms of fungal-bacterial interactions are likely widespread.

Wolfe notes that their findings suggest that certain mold species in artisan cheeses may disrupt the typical cheese development by using antibiotics. This knowledge can assist cheesemakers in determining which molds are harmful and how to control them in their cheese caves. Additionally, it provides insight into the idea that every time someone consumes artisan cheese, they are consuming the metabolites that microbes employ to compete and collaborate in communities.

The study was funded by a CAREER award from the National Science Foundation (Grant # 1942063).

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The American Society for Microbiology is one of the largest professional societies dedicated to the life sciences and is composed of 30,000 scientists and health practitioners. ASM's mission is to promote and advance the microbial sciences.

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