Rosa Rubicondior: Malevolent Designer News - How a Fungus Makes Its Host Destroy Its Own Brain

Beauveria bassiana on unidentified insect.

Fungus ‘hacks’ natural immune system causing neurodegeneration in fruit flies - University of Birmingham

If we are to believe creationists, their god created insects such as fruit flies, Colorado beetles, etc., and then set about devising ways to kill them with, amongst other pathogens, fungi that infect them and destroy them from inside.

One of the problems this supposedly intelligent designer had to overcome was the immune system it had given the insects in order to protect them from the pathogens it was designing to kill them.

According to an open access paper just published in PLOS Biology by a team led by Professor Alicia Hidalgo from School of Biosciences, The University of Birmingham, one species of parasitic fungus, Beauveria bassiana, cleverly turns its host's immune system against its host, making it destroy its own brain. Although this fungus does not affect mammals, so poses no threat to humans, the team warns that it is possible that another fungus could use a similar technique against mammals, including humans.

What information do you have on the fungus Beauveria bassiana? Beauveria bassiana is an entomopathogenic fungus, meaning it infects and kills insects. It belongs to the family Cordycipitaceae in the order Hypocreales. This fungus is widely used as a biological control agent against various insect pests due to its ability to parasitize a wide range of hosts, including beetles, aphids, grasshoppers, whiteflies, and mosquitoes.

Biology and Life Cycle

B. bassiana infects insects by attaching to their exoskeleton and penetrating it with specialized structures called appressoria.
Once inside the insect, the fungus proliferates, consuming its internal tissues and eventually killing the host.
After death, B. bassiana produces spores (conidia) on the insect’s body, which can spread to new hosts.

Applications in Biocontrol

Used commercially as a biopesticide in organic and integrated pest management (IPM).
Effective against agricultural pests such as the Colorado potato beetle (Leptinotarsa decemlineata), whiteflies (Bemisia tabaci), and thrips.
Some strains have been explored for controlling malaria-carrying mosquitoes.

Ecology and Distribution

Naturally found in soil worldwide.
Can persist in various environments by forming resistant spores.
Some strains have symbiotic or endophytic relationships with plants, potentially boosting plant resistance to herbivores.

Potential Uses Beyond Biocontrol

Studies suggest it may have antimicrobial properties.
Research is ongoing into its role in plant protection beyond direct insecticidal effects.

Fungus ‘hacks’ natural immune system causing neurodegeneration in fruit flies
Exposure to B. bassiana fungal caused Toll receptors to trigger cell death across fly brains
A fungal infection has been shown to trigger a fruit fly’s own immune system to destroy brain cells leading to signs of neurodegeneration, a new study has found.

The paper published in PLOS Biology today found that a fungus called Beauveria bassiana was able to make the fly’s innate immune system trigger a process that kills neurons and glia in the brain, leading to more than half of flies dying after seven days compared to half of control samples living for nearly 50 days.

In experiments conducted by a team of academics from the University of Birmingham, fruit flies were exposed to B. bassiana in infection chambers. After three days exposure, the fungus had penetrated the blood-brain barrier and had made its way into the central brain.

The scientists found that the fungus is able to trick the fly’s immune system agents called Toll receptors to release two different responses. The Toll-1 receptor triggered the release of antimicrobial peptides (AMPs) as expected, which attack and try to kill pathogens. However, the fungus also provoked Toll-1 to trigger the production of another molecule called Sarm, which suppresses the immune response and kills brain cells instead.

We have shown a process for how fungi have evolved to trick the immune system to get into the brain. The fungus is detected by the receptor that does a normal process to induce innate immunity, but in the brain this can also trigger an immune-evasion pathway that induces cell death in the host brain instead.

The key antagonist in the immune process is Sarm, a so-called master of destruction, that is causing cell death in the brain. The ability of B. bassiana to trick the fruit fly immune system into activating the master of destruction Sarm and kill cells enables spores to beat the blood-brain barrier and start feeding on brain cells.

Professor Alicia Hidalgo, lead author.
Brain Plasticity & Regeneration Lab
Birmingham Centre for Neurogenetics
School of Biosciences
University of Birmingham, Birmingham, UK.

From an evolutionary perspective, these findings highlight the ongoing arms race between hosts and pathogens, where hosts enhance their immune mechanisms while pathogens evolve new strategies to evade immunity.

It is important to stress that B. bassiana cannot affect humans. Some fungi have co-evolved with the host, so they will infect only particular hosts. B. bassiana infects multiple insect species, but not mammals. However, in principle, this study shows that other fungal infections could affect the human brain in analogous ways.

Dr Deepanshu N. D. Singh, first author.
Birmingham Centre for Neurogenetics
School of Biosciences
University of Birmingham, Birmingham, UK.

Publication:
Singh DND, Roberts ARE, Wang X, Li G, Quesada Moraga E, Alliband D, et al. (2025) Toll-1-dependent immune evasion induced by fungal infection leads to cell loss in the Drosophila brain. PLoS Biol 23(2): e3003020. https://doi.org/10.1371/journal.pbio.3003020

Abstract
Fungi can intervene in hosts’ brain function. In humans, they can drive neuroinflammation, neurodegenerative diseases and psychiatric disorders. However, how fungi alter the host brain is unknown. The mechanism underlying innate immunity to fungi is well-known and universally conserved downstream of shared Toll/TLR receptors, which via the adaptor MyD88 and the transcription factor Dif/NFκB, induce the expression of antimicrobial peptides (AMPs). However, in the brain, Toll-1 could also drive an alternative pathway via Sarm, which causes cell death instead. Sarm is the universal inhibitor of MyD88 and could drive immune evasion. Here, we show that exposure to the fungus Beauveria bassiana reduced fly life span, impaired locomotion and caused neurodegeneration. Beauveria bassiana entered the Drosophila brain and induced the up-regulation of AMPs, and the Toll adaptors wek and sarm, within the brain. RNAi knockdown of Toll-1, wek or sarm concomitantly with infection prevented B. bassiana-induced cell loss. By contrast, over-expression of wek or sarm was sufficient to cause neuronal loss in the absence of infection. Thus, B. bassiana caused cell loss in the host brain via Toll-1/Wek/Sarm signalling driving immune evasion. A similar activation of Sarm downstream of TLRs upon fungal infections could underlie psychiatric and neurodegenerative diseases in humans.

Introduction
Fungi can manipulate the behaviour of their insect hosts and induce neurodegeneration, ultimately causing host death and enabling fungal growth and reproduction [1–3]. How fungi can overcome protective brain barriers is unknown. Even exposure to fungal volatiles alone is sufficient to reduce life span, decrease dopamine levels, induce neurodegeneration and impair locomotion in fruit-flies [4,5]. This is concerning also for human health. Abundant fungal spores, mould and fungal volatiles are commonly found in indoor damp conditions [6,7]. Fungal spores have been found in the brains of Parkinson’s and Alzheimer’s disease patients, and fungal infections are emerging as drivers of neuroinflammation, neurodegenerative diseases and psychiatric disorders [8–14]. How fungi and neuroinflammation drive disease in the host brain is unknown [8,11].

The molecular mechanism underlying innate immunity in response to fungal infections is universally conserved and well known. It was originally discovered in the fruit-fly Drosophila melanogaster, where fungi lead to the activation of the Toll receptor [15–17]. This led to the discovery of Toll homologues in mammals, the Toll-like receptors (TLRs), and Tolls and TLRs across organisms have a universally conserved function in innate immunity [17–20]. Mammalian TLRs are pattern recognition receptors (PRR) that directly bind pathogens [20], but in Drosophila fungi are recognised by the PRR Gram Negative Bacteria Binding Protein 3 (GNBP3) instead [21]. This initiates a proteolytic cascade that activates Spätzle Processing Enzyme (SPE) that cleaves Spätzle (Spz), ligand of Toll-1 [20,22–25]. Signalling downstream of Toll-1 and TLRs proceeds via MyD88, triggering the nuclear translocation of the transcription factor Dif/NF-κB, which activates the expression of antimicrobial peptide (AMP) encoding genes [15,16,26,27]. In fruit-flies, AMPs include drosomycin (drs) and metchnikowin (mtk), which protect Drosophila from fungal infections [16,28–32].

However, in the nervous system, Toll receptors can also signal via the alternative adaptors, Weckle (Wek) and Sterile-α and Armadillo Motif containing protein (Sarm) [33,34]. Toll signalling can promote either cell survival via Wek-MyD88-NFκB or cell death via Wek-Sarm-JNK signalling downstream [34–36]. Tolls can also promote cell proliferation or quiescence, depending on cell context [34–36]. Sarm is expressed in neurons, and it is the universal, highly conserved inhibitor of MyD88 and TRIF signalling [26,37–40]. Sarm can be at the plasma membrane and associated with mitochondria, it can induce neuronal death via inhibiting the pro-survival function of MyD88, via activating JNK signalling and via NADase catalytic activity, which also drives neurite self-destruction [26,34,41–48].

There are nine Toll paralogues in Drosophila, and at least seven are expressed in the adult fly brain [34–36]. In the nervous system, Tolls have functions unrelated to immunity, in axonal connectivity, neurogenesis, cell survival, cell death, structural brain and synaptic plasticity [34–36,49–51]. Not all Tolls function equally, and Toll-1 is more likely to drive apoptosis than others [34–36]. Importantly, Toll-1 has the most prominent function in innate immunity [16,52,53].

Here, we asked whether fungal infections could induce neurodegeneration in the host brain via Toll-Wek-Sarm signalling. We used Beauveria bassiana, an entomopathogenic fungus that induces disease in over 700 arthropod species, a plant endophyte that protects plants against insects, can be used for pest control, and is a well-known activator of Toll signalling in Drosophila [21,54–62]. The upstream route to the activation of Toll-1 from GNBP3 to cleavage of Spz and activation of Toll signalling is very well known [15–17], thus was not explored further here. Instead, we asked: (1) whether B. bassiana could enter the brain and (2) could activate the alternative immune evasion Sarm pathway. We show that the fungus benefits from immune receptor signaling to cause cell death in the host brain.

Creationists are in a bind here because their cult leaders hold mutually contradictory views, both of which are the cult's 'proof' of intelligent design. On the one hand, William A. Dembski claims that any 'complex specified' genetic information must have been provided by an (unidentified, but not dissimilar to the Christian god) intelligent designer and there is no reason to suppose parasites are exempt from the genetic information being both complex and specified.

On the other hand, Michael J. Behe asserts that parasites are the result of 'genetic entropy' causing devolution [sic] from an initial created perfection, made possible by 'Sin' (which obviously has nothing to do with the 'Original Sin' in the Bible because that would mean ID is creationism). However, when parasitic pathogens such as Escherichia coli and Plasmodium falciparum have 'irreducibly complex' structures or processes, then they are definite proof of intelligent design.

So, fungi like Beauveria bassiana are either proof of intelligent design (Dembski) or proof of a natural process called 'devolution' [sic] and genetic entropy (Behe), unless they are irreducibly complex, then they are proof of intelligent design (Behe).

To anyone without a fundamentalist religion with a political agenda to push on the unsuspecting, however, these pathogens are easily understood as the result of a mindless, amoral natural process called an evolutionary arms race - one of the fundamental drivers of evolution by natural selection, especially in a parasite-host relationship.

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