ISME Journal study: Diverse Cyanopeptides Follow Distinct Temporal Succession Patterns in Freshwater Harmful Algal Blooms (DOI: 10.1093/ismejo/wrag026)
Environmental Toxicology study: Cyanopeptide Mixtures Induce Variable Synergistic and Antagonistic Effects Across Diverse Human Cell Lines (DOI: 10.1002/tox.70028)
Municipalities and federal agencies monitor U.S. waters for microcystins, a toxin produced by harmful algal blooms in Lake Erie, but a University of Michigan study shows that the blooms produce a greater range of potentially toxic compounds than previously known.
The researchers found that these compounds, called bioactive cyanopeptides, may overlap and interact with each other in ways that amplify their toxicity throughout the season. Now, they say, it will be important to characterize these compounds, determine their toxicity and examine how they interact with each other.

"A lot of people are aware of these algal toxins, but the big picture is that these harmful algal blooms are expanding with climate change, and they're a real threat to recreation, drinking water and ecosystems," said senior author Gregory Dick, professor of earth and environmental sciences and of environment and sustainability.
"What our paper shows for the first time is that in western Lake Erie, there really is a soup of these different compounds, and what's interesting is that there seem to be seasonal patterns in which these compounds pop up."
Their findings, published in The ISME Journal, are supported by the National Institutes of Health, National Institute of Environmental Health Sciences, National Science Foundation, Great Lakes Restoration Initiative, U.S. Geological Survey, and National Oceanic and Atmospheric Administration. The research was highly collaborative, involving scientists from U-M's Cooperative Institute for Great Lakes Research and Great Lakes Center for Freshwaters and Human Health, as well as NOAA and USGS.
To track what compounds were being produced in Lake Erie, the researchers examined samples from four NOAA Great Lakes Environmental Research Laboratory sampling stations in western Lake Erie. The samples were collected each month from May through October, from 2016 to 2022.
They then used a method to detect microbial DNA which told the researchers which bacteria were present. In tandem, the researchers also detected the presence of microbially produced compounds, including cyanotoxins like microcystins. This enabled the researchers to link the bacteria to the compounds they produced.
They found the usual suspects, such as microcystin, produced by the cyanobacteria Microcystis. But they also found several other compounds that had not yet been characterized in Lake Erie-and aren't tracked by conventional monitoring.
"Microcystin is the tip of the iceberg in terms of compounds that Microcystis and other cyanobacteria can produce," said Dick, who is also director of the Cooperative Institute for Great Lakes Research.

Lauren Hart, a U-M graduate student at the time and lead author of the study, found that the blooms occurred in three phases, beginning in the early spring when runoff and rain carry nitrogen into the lake.
The toxin microcystin dominates the first phase of blooms. Then, once nitrogen becomes depleted in the lake, other microbes step in to process the remaining nitrogen into forms usable for the production of other molecules later in the season. The second and third phases of algal blooms produce cyanopeptides called anabaenopeptins and aeruginosins, and then aerucyclamides.
Hart also recently discovered that these compounds can interact in ways that amplify or decrease their toxicity, researching the interactions after noticing that microcystins and anabaenopeptins were present at the same time in Lake Erie. In this study, published in Environmental Toxicology, Hart tested different combinations and dosages of microcystins and anabaenopeptins on three different human cell lines from the lung, liver and kidney.
"I wanted to ask, 'What does that mean for human health?'" she said. "We found that anabaenopeptins are as toxic as some of the most toxic microcystin congeners, but it's not a molecule that we monitor for."
Hart and colleagues also found that when they mixed microcystin and anabaenopeptin together, their effects amplified. Studies on cell lines don't necessarily translate directly to organisms, so the health risks to humans or animals remain unclear, but Hart's findings highlight the need for further research.
"In the first study, we characterized the molecules that exist in this 'forbidden soup' and that there were co-occurrences of these molecules. Then we tested the impact of those co-occurrences, and found that not only do they exist, they're of concern," Hart said.
"There needs to be more focus on what we are currently monitoring for, why we are currently monitoring it, and making sure we're including the bigger picture in our risk management models for large lakes."