Inside the Microbial Jungle: Tales from a Microbe Whisperer

ABOVE: Anne Madden is captivated by the endless possibilities that microbes have to offer from antibiotics to new beer flavors. Andres Ruzo

Anne Madden is a self-proclaimed “microbe wrangler.” Her inner explorer and scientist emerged during her undergraduate years at Wellesley College, during an internship in Costa Rica. Surrounded by the lush rainforest and passionate researchers, she studied plants and poison dart frogs. Madden quickly fell in love with this wondrous world of biology, and when she returned to Massachusetts, she searched for a way to keep doing research.

In her microbiology courses, she found her calling as she learned about another unknown jungle at a different scale—under a microscope. When Madden realized that the microbes around her not only grow into an explosion of colors on a Petri dish but also produce most of the antibiotics used to save lives, she pursued a pharmaceutical industry position. There, she cultured soil microbes to identify novel sources of antibiotics.¹

These beautiful spaces are a kind of time capsule of creatures. The samples that I was really looking at were these door trim samples of forgotten dust. It’s like a secret world.

 —Anne Madden, The Microbe Institute

But the urge for discovery led her back to an academic setting. She pursued her PhD in biology at Tufts University in the laboratory of behavioral ecologist Philip Starks, studying the microbiome of paper wasps. Wasp collecting took fieldwork to another level for Madden, taking her to old barns, orchards, and even Craigslist, where people were more than happy to donate their wasps for science. While cataloging microbes, she discovered and named a new fungus, Mucor nidicola, isolated from the inside of a paper wasp nest; she was thrilled by this since various Mucor species have utility in biotechnological applications.² When she shared the news with her dad, he said, “Oh, well I hope you discovered something to get rid of [the fungus].” While most people might be wary of fungi, Madden maintained an optimistic outlook. She viewed the world as her microbial oyster, brimming with countless novel species yet to be discovered.

Assembling an Atlas of Arthropods

In 2014, Madden’s interest in microbial habitats led her to the laboratories of Noah Fierer, a microbial ecologist at the University of Colorado Boulder, and Rob Dunn, an ecologist and evolutionary biologist at North Carolina State University. Over the next few years, they co-advised her on a series of postdoctoral research projects exploring the diversity of microbes in the environment. 

One of her notable projects branched off from a citizen science project called Arthropods of Our Homes. Homeowners around Raleigh, North Carolina volunteered their residences to help researchers create atlases of these unnoticed arthropod roommates to understand how the characteristics of the home and lifestyle may affect their diversity.³ Researchers collected samples by hand and swabbed for dust mites. On their first arthropod roster, they morphologically identified some of the most common home dwellers: cobweb spiders, ants, and book lice. While these arthropods were represented in at least 80 percent of homes, the researchers had only gotten a glimpse of the biodiversity in one part of North Carolina.

So, they expanded their work and enlisted the help of citizen scientists. Madden processed dust swabs from the indoor and outdoor door trims of more than 700 homes, including Fierer’s, in the continental United States. “She used some of the methods we use to study bacteria and fungi for arthropods. She has this really broad understanding of not just microbes, but also other groups of organisms, which makes her pretty unique,” remarked Fierer. To circumvent the limitations of morphology-based identification, Madden used environmental DNA and high-throughput marker gene sequencing to analyze the home dust. For dust control standards, Madden recalled crawling under faucets looking for book lice and other tiny critters. 

As she layered the data sets to analyze what arthropods were present—ranging from cockroaches to termites—she identified patterns in how various factors influenced their structures and lifestyles.⁴ For instance, arthropod diversity was higher in rural homes, homes with basements, and in homes with cats or dogs. “These beautiful spaces are a kind of time capsule of creatures. The samples that I was really looking at were these door trim samples of forgotten dust. It’s like a secret world,” said Madden.

The dust samples provided insights into the variety of arthropods living in homes across the US, uncovering 600 genera, including common housemates, such as spiders and flying insects. Dust mites, which can be serious allergens in homes, were more often associated with homes in humid regions of the country. But there was also evidence of the arthropods people eat, such as crabs and crayfish, from aerosolized DNA. One unexpected finding from door trim dust was evidence of fairy shrimp. Madden wondered if this was an error, but sure enough, the homeowner had pet fish, and their fairy shrimp meals contributed to the arthropod roster. “There’s this amazing diversity out there that we’re only beginning to understand,” said Fierer. Not long after completing this project, Madden shifted her focus to how these arthropods and their microbiomes might be useful to people.

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While studying house dust, Madden had also been looking at microbes inside wasps in a parallel project. Although many consider wasps to be pests—evident from her successful wasp removal services posted on Craigslist—Madden remarked, “There are so many things to learn about what microbes wasps transfer around their world or around vineyards.” 

In 2014, Madden received an interesting email request from Dunn for an education outreach project with John Sheppard, a bioprocess engineer at North Carolina State University. Dunn and Sheppard wanted to showcase the benefits of microbes and discover new wild yeast strains from nature for brewing beer—a beloved beverage celebrated for its diverse flavors. Madden, despite never having a beer up until that point in her life, was up for the challenge. Although she didn’t have any yeast, she told Dunn, “I have these wasps, and they carry yeast.” 

She’s a yeast whisperer. Anne is able to pay attention to yeast in their own terms, and she can think like a yeast better than anybody I’ve ever met. 

 —Rob Dunn, North Carolina State University

In a vineyard landscape during the summer months, different yeast species feed on the sugar in flower nectar and fruit, such as grapes. Then, wasps sip on the sugar of these yeasty grapes, and they inadvertently carry these microorganisms in their bellies and on to other fruit.^5,6 

This connection inspired Dunn and Madden to focus on the microbes within these pollinators. As Madden collected wasps and bees, she carefully transferred microbes from their bodies to a Petri dish. When a forest lush with microbes bloomed, she isolated the yeast candidates. Then, she analyzed the DNA from these candidates and ran them through a national database to ensure her picks didn’t cause disease. The final step was narrowing down the microbes with metabolisms of interest, such as alcohol fermentation, through biochemical and genetic tests. When Madden sent her shortlisted microbes to Sheppard, she had no idea whether they would work for brewing.

To her surprise, Sheppard had success with one of her microbes. The yeast was a species of Lachancea and was not known or utilized by the beer brewing community. “In this process, we learned that not only does this yeast make beer, but it makes a sour beer, which previously couldn’t be done by one single microorganism,” said Madden. “We found a yeast that people said couldn’t do what it could do, and so it changed our understanding as scientists of what yeast could do.”

Normally, sour beer can be a challenge for brewers because they have to add bacteria that produce lactic acid, which contributes to factors such as time and contamination. This fermentation process can take months or even years. However, this yeast could produce both the alcohol and the lactic acid needed to make a sour beer without requiring aging or adding other microorganisms. It produced a sour beer in roughly two weeks, which was unheard of in the brewing world. 

The team was thrilled by the potential of Madden’s single strain brewing yeast and what similar strains could accomplish in the future. “She’s a yeast whisperer. Anne is able to pay attention to yeast in their own terms, and she can think like a yeast better than anybody I’ve ever met,” said Dunn. “She has a magical ability to look into the microscopic world and think about how we might make human use of these magical things these organisms are undertaking.”

They debuted their wasp-derived beer at the World Beer Festival which harbored a blend of delightful flavors, ranging from sort of fruity to a bit floral. Madden described the taste as a “beautiful tartness.” Then, over the next few years, Madden and her colleagues hypothesized that wasps, bumblebees, and other sugar-seeking insects may prefer yeasts that produce floral and fruity aromas because these smells indicate a sugar resource.⁷ As such, yeast from these bugs might yield beers with new and tasty flavor profiles. Not long after, the researchers created a “bumblebeer” from bumblebee yeast which boasted a sweet honey taste without the addition of actual honey.

“A big part of the story, too, is you know, it’s one part luck, one part science, and knowing where to look for things and how to find them—wrangling the yeast—and then again, this other part of how humans work with microbes to deliver both excellent flavors,” said Madden.

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Exploring Why Microbes Matter with Science Communication

Aside from serving up arthropod atlases and buggy beer, Madden sought to serve her communities in another way. In 2020, she established The Microbe Institute, a nonprofit organization network for academic scientists who want to engage in science communication, companies that are working on microbial-related technologies, and artists who are looking for new tools in their craft. “I really wanted to create something like a NASA for the microbial world that could foster this discovery for a better tomorrow,” remarked Madden.

The Microbe Institute emerged around the same time as the COVID-19 pandemic. Because the whole world developed a contentious relationship with microbes, Madden felt that it was critical to highlight that not all microbes aim to kill people. Instead of making the world smaller, some microbes expand it through their numerous benefits to people. 

During lockdown, when many people could not venture far from home, Madden began The Global Lichen Hunt project, which encouraged people to venture into their backyards. There, they could identify lichen, share their findings with scientists, and learn more about the lichen around them. These data observations served as an ecological indicator for scientists to better understand the biology and distribution of the lichen, also noting how air pollution can influence their spread. 

Another partnership evolved when Brooke Jude, a molecular microbiologist at Bard College, heard Madden deliver a talk at a small regional meeting. They struck up a conversation and bonded over their microbial work. Jude’s research involves hunting for novel beneficial microbes in the local aquatic environment. Her first water sample from the Hudson River Valley watershed revealed naturally purple-pigmented bacteria. This purple pigment, called violacein, was not only beautifully colored but also exhibited antimicrobial properties.

Her communication is exquisite, and she’s very, very good at figuring out how to tell a story in the most positive light possible.

 —Brooke Jude, Bard College

Researchers have suggested that this pigment could help address the current amphibian conservation crisis, which is marked by declining populations often due to a chytrid fungal disease. These violacein-producing bacteria have been found to help amphibians combat this illness. Intrigued by these microbes, Jude wondered if the watershed harbored many more undiscovered bacterial species capable of producing this pigment. This curiosity provided a springboard for their collaboration.

“From there, we started thinking that a lot of our work overlapped in interesting ways, that some of the things that [Anne] was doing in The Microbe Institute, in terms of communicating about these projects that the general public could truly understand and sink their teeth into and enjoy and be passionate about. How do you get that word out?” said Jude.

So, Madden designed a few projects with Jude dedicated to finding more of these bacteria and understanding their biogeography. One part of this project involved citizen science, which encouraged science enthusiasts to sample local waterways, grow microbes, and upload data on whether they found purple-pigmented bacteria to aid researchers in finding new species of these helpful microbes. They also received funding from National Geographic to make educational materials to teach middle and high school students about these powerful, purple microbes. “Working with her, her communication is exquisite, and she’s very, very good at figuring out how to tell a story in the most positive light possible,” said Jude.

“It’s been really beautiful to witness what’s emerged from [The Microbe Institute’s partnerships], and as we continue to sort of scale in the coming years, with both projects and capacity, [we’re] really excited to see where that goes,” said Madden. Combining an air of whimsy with evidence-based education, she hopes to continue unveiling the microbial mysteries of the natural world. “Our goal is to democratize discovery, to really make [the] wonder of this microbial world possible for anyone who wants to explore it.”