A New Hybrid Fungus Found in Hospitals Is Linked to Lung Disease
By Jacob L. Steenwyk and Antonis Rokas
From the mythical minotaur to the mule, creatures created from merging two or more distinct organisms – hybrids – have played defining roles in human history and culture. However, not all hybrids are as fantastic as the minotaur or as dependable as the mule; in fact, some of them cause human diseases.
We are evolutionary biologists who are trying to understand why certain fungi infect hundreds of thousands of patients each year while others are harmless. We are particularly interested in infections caused by Aspergillus fungi, a group of molds – multicellular fungi that typically grow by forming networks of hairlike filaments – that can cause very serious infections in patients with weak immune systems. While examining Aspergillus strains isolated from patients with lung-related diseases, we unexpectedly discovered an Aspergillus hybrid that infects humans. This finding is significant not only because this is the first known example of a hybrid mold infecting humans but also because accurate identification of the species causing disease is key for managing fungal infections.
When Looking Through a Microscope Isn’t Close Enough.
For the last few years, our team at Vanderbilt University, Gustavo Goldman's team at São Paulo University in Brazil and many other collaborators around the world have been collecting samples of fungi from patients infected with different species of Aspergillus molds. One of the species we are particularly interested in is Aspergillus nidulans, a relatively common and generally harmless fungus. Clinical laboratories typically identify the species of Aspergillus causing the infection by examining cultures of the fungi under the microscope. The problem with this approach is that very closely related species of Aspergillus tend to look very similar in their broad morphology or physical appearance when viewing them through a microscope.
Interested in examining the varying abilities of different A. nidulans strains to cause disease, we decided to analyze their total genetic content, or genomes. What we saw came as a total surprise. We had not collected A. nidulans but Aspergillus latus, a close relative of A. nidulans and, as we were to soon find out, a hybrid species that evolved through the fusion of the genomes of two other Aspergillus species: Aspergillus spinulosporus and an unknown close relative of Aspergillus quadrilineatus. Thus, we realized not only that these patients harbored infections from an entirely different species than we thought they were, but also that this species was the first ever Aspergillus hybrid known to cause human infections.
Several Different Fungal Hybrids Cause Human Disease.
Hybrid fungi that can cause infections in humans are well known to occur in several different lineages of single-celled fungi known as yeasts. Notable examples include multiple different species of yeast hybrids that cause the human diseases cryptococcosis and candidiasis. Although pathogenic yeast hybrids are well known, our discovery that the A. latus pathogen is a hybrid is a first for molds that cause disease in humans.
(Left) Candida yeasts live on parts of the human body. Imbalance of microbes on the body can allow these yeasts, some of which are hybrids, to grow and cause infection. (Right) Cryptococcus yeasts, including ones that are hybrids, can cause life-threatening infections in primarily immunocompromised people. Centers for Disease Control and Prevention
Why certain Aspergillus species are so deadly while others are harmless remains unknown. This may in part be because combinations of traits, rather than individual traits, underlie organisms' ability to cause disease. So why then are hybrids frequently associated with human disease? Hybrids inherit genetic material from both parents, which may result in new combinations of traits. This may make them more similar to one parent in some of their characteristics, reflect both parents in others or may differ from both in the rest. It is precisely this mix and match of traits that hybrids have inherited from their parental species that facilitates their evolutionary success, including their ability to cause disease.
The Evolutionary Origin of an Aspergillus Hybrid.
Multiple evolutionary paths can lead to the emergence of hybrids. One path is through mating, just as the horse and donkey mate to create a mule. Another path is through the merging or fusion of genetic material from cells of different species.
It is this second path that appears to have been taken by our fungus. A. latus appears to have two of almost everything compared to its parental species: twice the genome size, twice the total number of genes and so on. But unlike other hybrids, which are often sterile like the mule, we found that A. latus is capable of reproducing both asexually and sexually.
But how distinct were the parents of A. latus? By comparing the parts contributed by each parent in the A. latus genome, we estimate that its parents are approximately 93% genetically similar, which is about as related as we humans are with lemurs. In other words, A. latus, an agent of infectious disease, is the fungal equivalent of a human-lemur hybrid.
How A. Latus Differs From its Parents.
Elucidating the identity of closely related fungal pathogens and how they differ from each other in infection-relevant characteristics is a key step toward reducing the burden of fungal disease. For example, we found that A. latus was three times more resistant than A. nidulans, the species it was originally identified as using microscopy-based methods, to one of the most common antifungal drugs, caspofungin. This result provides a clear example of the potential importance of accurate identification of the Aspergillus pathogen causing an infection.
We also examined how A. latus and A. nidulans interact with cells from our immune system. We found that immune cells were less efficient at combating A. latus compared to A. nidulans, suggesting the hybrid fungus may be trickier for our immune systems to identify and destroy.
In the midst of the COVID-19 pandemic, our quest to understand Aspergillus pathogens is becoming more urgent. Growing evidence suggests that a fraction of COVID-19 patients are also infected with Aspergillus. More worrying is that these secondary Aspergillus infections can worsen the clinical outcomes for those infected with the novel coronavirus. That being said, we stress that little is known about Aspergillus infections in COVID-19 patients due to a lack of systematic testing, and none of the infections identified so far appear to have been caused by hybrids.
So, when it comes to hybrids, some are fantastic (the minotaur), some are helpful (the mule) and some are dangerous (Aspergillus latus). Understanding more about the biology of Aspergillus latus may help in our understanding of how microbial pathogens arise and how to best prevent and combat their infections.
Jacob L. Steenwyk is a Graduate Student of Biological Sciences, Vanderbilt University.
Antonis Rokas is a Cornelius Vanderbilt Chair in Biological Sciences, Professor of Biological Sciences and Biomedical Informatics, and Director of the Vanderbilt Evolutionary Studies Initiative, Vanderbilt University.
Disclosure statement: Jacob L. Steenwyk receives funding from the Howard Hughes Medical Institute through the James H. Gilliam Fellowship for Advanced Study program.
Antonis Rokas and his laboratory receives funding from the National Science Foundation, the John Simon Guggenheim Memorial Foundation, the Burroughs Wellcome Trust, the National Institutes of Health, the Beckman Scholars Program, the March of Dimes, the Howard Hughes Medical Institute, and Vanderbilt University.
Reposted with permission from The Conversation.
At first glance, you wouldn't think avocados and almonds could harm bees; but a closer look at how these popular crops are produced reveals their potentially detrimental effect on pollinators.
Migratory beekeeping involves trucking millions of bees across the U.S. to pollinate different crops, including avocados and almonds. Timothy Paule II / Pexels / CC0<p>According to <a href="https://www.fromthegrapevine.com/israeli-kitchen/beekeeping-how-to-keep-bees" target="_blank">From the Grapevine</a>, American avocados also fully depend on bees' pollination to produce fruit, so farmers have turned to migratory beekeeping as well to fill the void left by wild populations.</p><p>U.S. farmers have become reliant upon the practice, but migratory beekeeping has been called exploitative and harmful to bees. <a href="https://www.cnn.com/2019/05/10/health/avocado-almond-vegan-partner/index.html" target="_blank">CNN</a> reported that commercial beekeeping may injure or kill bees and that transporting them to pollinate crops appears to negatively affect their health and lifespan. Because the honeybees are forced to gather pollen and nectar from a single, monoculture crop — the one they've been brought in to pollinate — they are deprived of their normal diet, which is more diverse and nourishing as it's comprised of a variety of pollens and nectars, Scientific American reported.</p><p>Scientific American added how getting shuttled from crop to crop and field to field across the country boomerangs the bees between feast and famine, especially once the blooms they were brought in to fertilize end.</p><p>Plus, the artificial mass influx of bees guarantees spreading viruses, mites and fungi between the insects as they collide in midair and crawl over each other in their hives, Scientific American reported. According to CNN, some researchers argue that this explains why so many bees die each winter, and even why entire hives suddenly die off in a phenomenon called colony collapse disorder.</p>
Avocado and almond crops depend on bees for proper pollination. FRANK MERIÑO / Pexels / CC0<p>Salazar and other Columbian beekeepers described "scooping up piles of dead bees" year after year since the avocado and citrus booms began, according to Phys.org. Many have opted to salvage what partial colonies survive and move away from agricultural areas.</p><p>The future of pollinators and the crops they help create is uncertain. According to the United Nations, nearly half of insect pollinators, particularly bees and butterflies, risk global extinction, Phys.org reported. Their decline already has cascading consequences for the economy and beyond. Roughly 1.4 billion jobs and three-quarters of all crops around the world depend on bees and other pollinators for free fertilization services worth billions of dollars, Phys.org noted. Losing wild and native bees could <a href="https://www.ecowatch.com/wild-bees-crop-shortage-2646849232.html" target="_self">trigger food security issues</a>.</p><p>Salazar, the beekeeper, warned Phys.org, "The bee is a bioindicator. If bees are dying, what other insects beneficial to the environment... are dying?"</p>
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