Climate Change's Silent Threat: The Fungal Awakening

see the episode substack for more detail

We're witnessing the quiet emergence of a global threat that could redefine public health in the coming decades. While the world fixates on flashy disaster headlines and political theater, a more insidious danger is evolving in the shadows of our warming planet—pathogenic fungi that are adapting to higher temperatures, including our body temperature, with alarming speed.

The recent Heliox podcast deep dive into fungal pathogens and climate change revealed a reality that should disturb us all: the environmental shifts we've set in motion are creating perfect conditions for fungal evolution that threatens human health in ways we're only beginning to understand.

Impact of climate change and natural disasters on fungal infections

Why Infections by Bacteria, Viruses and Fungi Will Increase In The Future?

Evolutionary origin and population diversity of a cryptic hybrid pathogen

Rates of infection with other pathogens after a positive COVID-19 test versus a negative test in US veterans (November, 2021, to December, 2023): a retrospective cohort study

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Transcript

0:25

All right, welcome to the Deep Dive. Today we're going to be talking about something pretty fascinating and something I think is only going to become more important as time goes on, and that's the connections between fungal pathogens, climate change, and even natural disasters. And you flagged some really compelling recent scientific research for us, and what we're going to try to do today is... you know, really pull out the key insights from these different papers. Absolutely. And make sense of it all for you, the learner. Right. So to get us started, why don't you tell us a little bit about the research that we're going to be looking at today? Well, I think the first thing to understand is that, you know, we have to look at how these different forces are all kind of coming together and interacting with, to kind of impact our health and the environment around us. And so, you know, to get started, the first paper we have is from Nature Communications. And the title is Evolutionary Origin and Population Diversity of a Cryptic Hybrid Pathogen. And this paper really zooms in on a specific fungus called Aspergillus lattice. Now, it's described as cryptic, and we'll get into that. But it's a very interesting paper that really goes into some depth on this particular fungus. Yeah, sounds pretty interesting. And then, you know, you also flagged another paper for us, which kind of takes a bit of a broader look at all of this. Yeah. So taking a step back from just that one particular fungus, we can get a broader perspective from the Lancet microbe. OK. And they have this great review called Impact of Climate Change and Natural Disasters on Fungal Infections. So this looks at kind of the bigger picture in terms of how environmental shifts are influencing various fungal pathogens and contributing to disease outbreaks. All right. And then last but not least, you also sent over a Twitter thread by at adjustin46. And while this one is mostly about COVID-19, it does raise some interesting points about co-infections. Absolutely. Which seems pretty relevant for today's topic. So for you... The learner, the goal of this deep dive is to really, you know, connect these seemingly disparate pieces. Right. We want to understand how climate change and natural disasters are shaping the world of fungal infections, including, you know, the emergence of the behavior of specific fungi like Aspergillus lattice that we just mentioned earlier. And then really just kind of grasp the broader significance for human well-being. Right. Right. OK. So let's dive into the cryptic world of Aspergillus lattice first. All right. This Nature Communications paper, you know, it gives us a really good detailed look at Aspergillus lattice. And one of the things that I found really interesting was that it's an allodeployed hybrid. Yeah. Yeah. Now, that sounds very technical. Right. But in very simple terms, what does that mean for this fungus? Well, think of it like this. Aspergillus lattice has essentially inherited a double set of genetic instructions, a genome that's roughly twice the size and contains twice the number of genes compared to its close relatives. Wow, that's incredible. So, you know, the researchers discovered this by looking at its genetic makeup, you know, sequencing the genome. Right. And they found that there are two copies of the genome. of most Busco genes. Now these are kind of like essential single copy genes that are usually found in just one version, right? Okay. But in a lattice, a surprising 96.68% of these were duplicated. So almost a complete doubling of these essential genes. Yeah, it's pretty remarkable. So how else did they figure out or how else did they determine that alatus was a hybrid? So they use something called macrosyntony analysis. Okay. And so what that does is imagine you're comparing the arrangement of houses on two different streets. Okay. Right? To see how similar they are. Okay. Macrosyntony analysis does kind of a similar thing with genes on chromosomes. Okay. so what they found was that large chunks of the a lattice genome had the same gene order as parts of the genomes of two other species aspergillus spinolosporus and aspergillus quadrillioniitis wow so this strongly suggested that a lattice originated from a fusion of you know, these two or at least closely related species of fungi. So it's like taking, you know, significant portions of the genetic coat from, you know, two different fungal species and combining them. It's really incredible. Wow. And was there anything else that... that they found or any other, you know, methods that they used to kind of come to that conclusion? So further evidence came from, you know, phallogenomics, which is like building a family tree using genetic information. Okay. And so by analyzing over 3,700 of those Biscu genes. They were able to trace the origin of each copy. Okay. One copy of each gene appeared to come from A. spinulosporus while the other came from a close but as yet unknown relative of a quadrilineatus. So these duplicated genes that arise from such a hybridization event are called onalogues. Onalogues. Got it. So it's not just, you know, a random doubling but they can actually see you know, kind of the fingerprints of these two parental lines in alatus. That's some impressive detective work. Yeah. And, you know, I'm kind of curious, you know, you have all of these extra genes now, right? So did the fungus just discard the duplicates? It's interesting that you asked that. So they found that on average, 91.63% of these onologues have been retained in the alatus genome. Wow. So this suggests that having these extra gene copies has likely provided some sort of evolutionary advantage and that the genome has become quite stable over time. Right. They also found very little evidence of recombination, which is like genetic mixing and matching between the two sets of parental genes across the 22 isolates that they studied that had very complete genomes. Oh, wow. So it seems like this hybrid fungus isn't some recent unstable newcomer. No, it's something that has been around for... for quite some time and its genetic structure has been established. It seems so, yeah. Yeah, that's really fascinating. And speaking of time, I mean, did the paper give any indication of when this hybridization event might have occurred? They did. So using what are called relaxed molecular clock analyses, which look at the rate of genetic changes over time, They estimate that a lattice originated somewhere between 13.7 and 13.1 million years ago. Wow. So it's an ancient fungus. It's a very, very deep evolutionary history. That's incredible. Yeah. So this hybrid has been around for a very long time. That's amazing. Okay. So we've got this really long established hybrid fungus. Yeah. What else did the researchers uncover about its genes and what they do? So they looked at the distribution of core genes, which are present in all the A-lattice samples that they looked at, and accessory genes, which vary between different samples. And what they found was that core genes... are much more common overall. However, the collection of accessory biosynthetic gene clusters, or BGCs, is actually larger than the core BGCs. And BGCs, those are groups of genes responsible for producing things like antibiotics or other specialized molecules, right? Exactly. So think of them as like little fungal factories that produce various molecules. And what's really intriguing is that the products of many of these BGCs and alitis are still unknown. So this suggests that this fungus might have the potential to produce novel compounds, or perhaps some of these gene clusters are just no longer actively producing anything. Okay. They also found that the proteins that are produced by core and soft core genes tend to be longer and are more likely to have a known function compared to those from shell and cloud genes, which are more variable. And surprisingly, the soft core BGCs actually contain fewer genes on average than the other types. Oh, wow. Interesting. So the consistent set of genes... you know, in a latest is pretty well understood. But but the more variable genes, particularly in those BGCs are are kind of a mystery box in terms of what they can do. That's a great way to put it. Yeah. And that just sounds like, you know, a really fertile area for future research. Oh, absolutely. Okay, so what about how these genes are actually used? Is there a preference for, you know, the genes from one parental genome over the other? Well, that's a really insightful question. So they investigated gene expression levels at both 30 degrees Celsius and 37 degrees Celsius. Okay. Which are relevant temperatures, you know, for its growth in the environment and potentially in association with, you know, mammals. Right. What they discovered was that the transcript abundances... which basically tells us how much of each gene's blueprint is being used to create proteins, like how often a recipe is being followed in a kitchen, were almost equal from both the A. spinulosperous-like and the A. quadrilineatus-like parts of the genome at both temperatures. Gotcha. They also observed that codon usage bias, which can influence how efficiently a gene's message is translated into a protein, was similarly optimized in both subgenomes. So it's a pretty balanced operation with both parental contributions actively involved in the fungus's life at those temperatures. Yeah. It's really remarkable. Yeah. Did they see any... You know, any shifts in gene usage when they changed the temperature? Yes. So they did a differential expression analysis. Okay. And what they found was that there was a similar number of genes that were significantly more or less active in each of the parental genomes. Okay. When they shifted between 30 degrees and 37 degrees Celsius. Okay. Interestingly, many of the analogs that showed differential expression. Right. Displayed what are called conserved responses. Right. Meaning both copies of the duplicated gene reacted in the same way to the temperature change. For example, they saw an increase in activity of genes involved in the glutathione metabolic process, which is known to help organisms cope with heat stress. Yeah, that makes sense, you know, kind of a coordinated defense against a changing environment. Exactly. Exactly. But were there also instances where the analogs behaved differently? Absolutely. Where one copy of the gene responded to the temperature shift and the other one didn't? Right. So they observed subgenome-specific responses as well. Okay. Okay. In some onalog tears, one copy from one parent would become more active, while the copy from the other parent might not change or even become less active. Hmm. Interesting. So this indicates that both parental genomes are contributing to the overall functioning of the fungus. Right. Right. But they also have their own distinct ways of responding to environmental cues. Right. So it's kind of like this, you know, this hybrid nature gives it a broader range of tools to handle different, you know, different conditions. Absolutely. So it's got, you know, shared and specialized responses, you know, from its duplicated genes. Exactly. Yeah, that's a pretty cool, you know... set up. It's a very, you know, advantageous setup for sure. Yeah. Okay. So now let's circle back to why it's called a cryptic pathogen. You know, what makes it cryptic and what are the implications of that? Well, so the study really emphasizes that this detailed genetic characterization that they've done is really vital for developing, um, accurate diagnostic tests. Okay. And the reason for that is because A. Lattice can be quite difficult to distinguish from other Aspergillus species just based on its physical appearance alone. Okay. So these specific genetic markers can really help us improve our ability to track its spread and understand its actual role in causing disease. So we need to be able to really identify it to know how prevalent it is and what kind of health risks it might pose. Absolutely. Okay. And this leads us to the interesting connection with COVID-19 that came up in that Twitter thread. Right. So the researchers noted that six clinical isolates, basically samples taken from patients that were initially misidentified as a latest, were actually found to have come from individuals who were also infected with COVID-19. Oh, wow. Wow. So while there's already some research on Aspergillus cumigatus as a co-infecting agent in COVID-19 patients, the discovery of these a-latus co-infections adds to the growing body of evidence that other Aspergillus species can also establish themselves in patients who are battling SARS-CoV-2. Yeah, that's a really interesting connection. And, you know, it really... If we're seeing these fungal co-infections, you know, in the context of viral illnesses, it really underscores the importance of the kind of accurate identification that this study makes possible. Absolutely. Yeah. Okay. So that was a really, you know, fascinating deep dive into aspergillus sleep. latest. Now let's shift gears a little bit, you know, and look at the broader impact of climate change on the fungal world, drawing on some of the insights from the Lancet Microbe Review. Yeah. So this review really highlights how, you know, the long-term shifts in temperature and weather patterns that are caused by climate change are having a far-reaching impact on pathogens, their hosts, and where they can survive. Okay. And as the authors point out, it's often the populations who are most vulnerable to infectious diseases. Right. Who are going to bear the brunt of these climate-driven changes. Yeah, that's a sobering thought. Absolutely. And, you know, with regards to fungi specifically... The review really emphasizes that many pathogenic fungi, you know, they're not just surviving these increasing global temperatures. They're actually thriving and adapting to the heat. Yeah. And potentially becoming more dangerous. Exactly. And a key example that they discuss is Candida auris, you know, this relatively recent fungal pathogen that has demonstrated significant tolerance to higher temperatures. Right. Including those within the human body. Right. So the review also points out how climate change has likely contributed to the expansion of... endemic fungal diseases like kakiriori mycosis and histoplasmosis into new geographical areas, as well as affecting fungi that impact animals and plants. And we can't overlook the fungal pathogens that attack plants, which are also evolving in response to climate change and posing an increasing threat to our food supply. Right, right. So it's not just about the direct threats to human health, but it's also the consequences for agriculture could have... significant indirect impacts on us as well. Absolutely. Yeah. So how exactly are these fungi managing to adapt to all of this increasing heat? Right. What are some of their strategies? Well, the review details several... You know, pretty remarkable mechanisms. Okay. One important one is the increased production of heat shock proteins, or HSPs, which help to protect other proteins from damage at high temperatures. Right. They also mention the activation of specific signaling pathways like HSF, HOG, and calcineurin signaling, which help the fungus cope with various stresses. Additionally, they note increased expression of amino acid permices, which are involved in taking up nutrients, and the enhanced production of melanin, that dark pigment that we often see in fungi. Melanin actually acts like a shield, providing protection not only against heat, but also against other environmental stresses like changes in pH, pH, pH, pH, pH. heavy metals, and even radiation. So it's kind of like a fungal, you know, Swiss Army knife, offering defense against multiple threats. That's a great way to put it. Are there any other kind of adaptations that they're using? Yeah. So they're also modifying their cell walls, making them more robust and less permeable. Okay. Some fungi are even changing their ploidy, essentially increasing the number of copies of their entire genome. Wow. That's incredible. Increased mutation rates Possibly driven by the activation of mobile genetic elements. Right. Can also accelerate the pace of adaptation. And they're observing enhanced morphogenesis, which just means changes in their physical form as well as increased formation of biofilms. Right. Those sticky communities of microbes that can be very resistant to both antifungals and... and the host's immune defenses. Right. Finally, they can ramp up the production of enzymes that detoxify harmful substances and metabolites that help stabilize their proteins. So they've got, I mean, that's an incredible array of adaptive strategies. It's quite impressive, actually. Yeah, it really is. And the review suggests that these adaptations, you know, not only help them survive the heat, but they can actually make them more harmful to us. Precisely, yeah. So these mechanisms can lead to increased virulence, meaning they're better at causing disease, and an enhanced ability to evade our immune systems, making it harder for our bodies to fight them off. Yeah, that's not good. No, not at all. So the review also touches on how... Climate change can influence other factors that affect fungal ecosystems and our own susceptibility to infections, things like pollution, microplastics, and even changes in UV exposure. Yeah. So they highlight that pollution in water bodies can actually create more favorable conditions for fungal growth and increase fungal diversity. Including pathogenic species And the reason for that is that Some pollutants can actually provide A food source Or they can alter the environment in ways that Benefit fungi This is actually a concern even in industrialized nations The role of microplastics Is also really interesting So while some fungi can actually break down plastics, the widespread presence of microplastics in water could inadvertently provide a surface for fungal growth and potentially even contribute to the development of antifungal resistance. Oh, wow. Yeah, it's kind of a double-edged sword, increased UV exposure, which can be a consequence of... You know, a thinning ozone layer due to climate change can negatively impact human immunity, making us more vulnerable to infections in general. Right. OK. And they even mention a slight decrease in average human body temperature. Oh, wow. Which could theoretically affect our natural resistance to certain fungi. That's really interesting about a human body temperature. And, you know, the review also draws a connection between climate change, increased fungicide use in agriculture, and the rise of antifungal resistance in human path. This is a really critical point. Right. So as climate change is driving the evolution of fungal plant pathogens, there's an increased reliance on fungicides in agriculture to protect crops. Right. Unfortunately, many of these agricultural fungicides belong to the same chemical classes as the antifungals we use in human medicine. Oh, wow. Particularly the azole class. Right. So this widespread environmental exposure... can drive the development of resistance in human pathogens like Aspergillus fumigatus and Fusarium sippy. Right. And even more worryingly, some of the newer fungicides being developed for agriculture share their mechanisms of action with novel antifungal drugs that are currently in development for human use. Oh, wow. So this could potentially lead to resistance to these new drugs even before they become widely available. That's a pretty scary prospect. It's deeply concerning. Yeah, potentially losing these future antifungal treatments, you know, before we even have a chance to use them. Yeah. Because of resistance that's developing in agricultural settings. Exactly. Yeah. So it seems like climate change is really driving... you know, shifts in fungal infection patterns in a few different ways, right? We have the emergence of new threats. Right. We have the spread of existing ones. And then we have this increasing difficulty in treating them due to resistance. Exactly. Yeah. It's a pretty complicated situation. It's definitely multifactorial. Yeah. So the review emphasizes that warming temperatures are a key factor in the emergence of new human fungal pathogens. Yeah. prime example of a pathogen that's hypothesized to have emerged, at least in part, due to these rising temperatures. And it's not just, you know, entirely new species, but the geographical ranges of established endemic fungal diseases are also, you know, on the move. Absolutely, yeah. So they discuss the expansion of endemic mycosis like coccidiodomycosis, histoplasmosis, and blastomycosis into regions where they haven't historically been prevalent. Even the way that fungal spores are dispersed through the air can be affected by warmer temperatures and increased atmospheric turbulence, influencing the distribution of fungal pathogens. Okay. And they also note that several skin and eye fungal infections which thrive in warm and moist environments are also likely to be influenced by climate change. Yeah. So climate change is really, you know, acting as this powerful force, you know, reshaping the entire landscape of fungal diseases. It really is. Yeah. Okay. So let's move on to the third piece of our puzzle today, which is natural disasters. Right. The Lancet Microbe Review also explores how, you know, these events, which are becoming more frequent and intense due to climate change, can trigger outbreaks of fungal diseases. Yeah, and this is a really crucial connection to understand, because natural disasters often create this perfect combination of factors that can dramatically increase both our exposure to fungal pathogens and our exposure to fungal pathogens. and/or susceptibility to infection. Oh, okay. So it's kind of a double whammy. Right. So the review outlines several different ways this can happen. Yeah. And I think one of the most direct is through traumatic injuries that provide an easy entry point for fungi into the body. Exactly. So cuts, scrapes, any kind of break in the skin's protective barrier can allow fungi from the environment to gain access. And the contamination of wounds with organic matter, which is common after disasters, can lead to serious mold infections in the skin and soft tissues. Yeah, that makes sense. And, you know, beyond those physical injuries, natural disasters, they also take a toll on our immune systems. Absolutely. So the immense psychological stress and the physical trauma associated with disasters can weaken our immune defenses. Right. Making us much more vulnerable to... opportunistic fungal infections. Right. The ones that wouldn't normally cause a problem in a healthy person. Right. Right. And then there's the issue of fungal spore dispersal. Okay. Events like wildfires, volcanic eruptions, and strong winds can release vast quantities of fungal spores into the air. Right. Potentially leading to widespread exposure and respiratory infections. Right. even in populations far removed from the immediate disaster zone. And then you have the conditions in the aftermath of floods and heavy rainfall that can also be ideal for fungal growth. Yes. The increased humidity and the water damage to buildings create a perfect breeding ground for molds. Right. And this can significantly elevate the risk of respiratory problems and chronic diseases due to that prolonged mold exposure. Okay. The review even presents a compelling hypothesis about tsunamis. Oh, wow. Potentially introducing pathogenic waterborne microbes to land, which may have been the case with Cryptococcus gaudii, Pacific Northwest following a major earthquake in Alaska back in 1964. So a major geological event having these long-term biological consequences in a distant location, that's pretty fascinating and also a bit unsettling. Yeah, definitely. Okay, so the review also provides some specific examples of fungal outbreaks that have followed natural disasters. They do. So they mention cases of severe soft tissue infections caused by the fungus Rhizopus aresis after a volcanic eruption in Columbia in 1985. The devastating Indian Ocean tsunami in 2004 led to a number of cases of invasive mold infections linked to fungi like Apophysomyces elegans and Aspergillus. More recently, we saw an increase in invasive mold infections after Hurricane Harvey in Houston in 2017. Right. And then there's the tragic example of pulmonary hemorrhages in infants. Right. That were linked to the Mold Statubatris Charterum after flooding in 1994. Wow. And even the long-term health consequences of hurricanes like Katrina and Sandy. Right. Include an increased risk of respiratory symptoms and chronic diseases from mold exposure in damaged homes. Right. So it really illustrates how, you know, these large scale environmental catastrophes have these very specific and sometimes unexpected impacts on fungal infections. Absolutely. Yeah. And the review also touches on the effects of wildfires on soil ecosystems. So wildfires can drastically alter the diversity and the function of microbial communities in the soil. Right. And this includes fungal populations. And there's actually this emerging field of pyroarobiology, which is specifically investigating how viable microbial life can be aerosolized and transported by smoke from wildfires, potentially influencing the distribution and the spread of fungal species. So it sounds like fungal outbreaks following natural disasters are a pretty significant public health concern. They are. And perhaps one that doesn't get the attention that it deserves. Yeah. And the review actually explicitly suggests that these outbreaks are likely underreported. This could be due to a number of things. You know, the overwhelming challenges and disaster-stricken areas where... Immediate survival needs take precedence. Right. A lack of readily available diagnostic tools and trained health care professionals to identify fungal infections in these chaotic settings. And unfortunately, limited research funding directed towards this specific intersection of disasters and fungal disease. So we may only be seeing the tip of the iceberg when it comes to the true burden of fungal diseases following natural disasters. It seems very likely. Yeah. Yeah. Okay, well, this has been a really in-depth and fascinating exploration of how all these factors are interconnected. Yeah, it's an incredibly complex and important topic. Yeah, it really is. So let's wrap up with some key takeaways for you, the learner. Absolutely. So, you know, we've seen how Aspergillus lytus is this really compelling example of a cryptic hybrid pathogen. Right. With a long evolutionary history and even the potential to co-infect COVID-19 patients. Right. You know, this highlights... hidden diversity within this Aspergillus genus and the possibility of, you know, a lot of underdiagnosed infections. Right. So understanding its genetics is really key to better diagnostics. Right. We've also learned that climate change is this, you know, really powerful driver in the adaptation, emergence and spread of a wide variety of fungal pathogens. You know, they're becoming more tolerant to heat, potentially more virulent and expanding their geographical ranges, posing new threats to both human health and agriculture.