Are fungal pathogens manipulating human behavior?

 

Fungal infection of brain tissue (Wikicommons, CDC). Some fungi persist in the human brain for years and begin to harm their host only in old age. What were they doing previously?

 

 

I've published a paper on manipulation of human behavior by fungal pathogens. Here's the abstract:

 

Many pathogens, especially fungi, have evolved the capacity to manipulate host behavior, usually to improve their chances of spreading to other hosts. Such manipulation is difficult to observe in long-lived hosts, like humans. First, much time may separate cause from effect in the case of an infection that develops over a human life span. Second, the host-pathogen relationship may initially be commensal: the host becomes a vector for infection of other humans, and in exchange the pathogen remains discreet and does as little harm as possible. Commensalism breaks down with increasing age because the host is no longer a useful vector, being less socially active and at higher risk of death. Certain neurodegenerative diseases may therefore be the terminal stage of a longer-lasting relationship in which the host helps the pathogen infect other hosts, largely via sexual relations. Strains from the Candida genus are particularly suspect. Such pathogens seem to have co-evolved not only with their host population but also with the local social environment. Different social environments may have thus favored different pathogenic strategies for manipulation of human behavior.

 

Please feel free to comment.

 

Reference

 

Frost, P. (2020). Are Fungal Pathogens Manipulating Human Behavior? Perspectives in Biology and Medicine 63(4): 591-601. https://doi.org/10.1353/pbm.2020.0059

 

I was really something

I was really something (2016), by Judith Carlin. A fungus may live in your brain for years while meddling only as much as necessary with your neurons. Beyond a certain age it gets less benefit and has less incentive to keep you mentally healthy. One result may be Alzheimer's.



Behavior manipulation has been perfected by many organisms: viruses, bacteria, worms, and insects. Fungi, however, seem to be the champions:

Fungi probably represent a special case study in this general field because of several unique factors peculiar to this Kingdom. The first and most prominent is the range and complexity of behavioral manipulation by fungi of arthropods. [...] It is difficult and perhaps futile to rank manipulation across different kingdoms of life and argue that fungal manipulation is more complex than that observed when the manipulator is in the Kingdom Animalia (eg, trematodes). However, what is clear is that the diversity of strategies is greater than that observed in other groups. In addition, it is evident that behavioral manipulation has arisen multiple times independently. (Hughes et al. 2016)

You've probably heard about "zombie ants." A fungus invades an ant's brain and makes it leave its nest, climb up a plant, and fix itself in place with its mandibles. The fungus then kills the ant, and a fruiting body sprouts from behind the ant's head and showers spores onto the forest floor below.

There are other examples. A fungus invades the body of a flying insect and causes a hole to form on the side of the abdomen. It then releases spores through that hole while its host is flying. The infected body gradually falls apart, except for its nervous system and its wings. Is the insect still alive? Not really. The bits and pieces that remain have become extensions of the fungus (Hughes et al. 2016).

Other fungi imitate the smell or visual appearance of a sexually receptive female to lure male insects, who then become infected (Hughes et al. 2016).

In the above cases, the fungus mutilates and kills its host in ways that are not only ghastly but also easy to observe and study. But what about the more subtle cases where the host's behavior is simply altered? Those are the ones we know much less about. Our knowledge is biased toward the most obvious cases of infection. As Greg Cochran observed:

The most conspicuous transmission chains occur when disease manifestations are externally apparent in a high proportion of infected individuals, when they occur soon after the onset of infection, and when contact between infected and susceptible individuals is easy to observe. Under these circumstances chains of transmission are apparent through everyday experience. (Cochran et al. 2000)

Even when we can detect the presence of a pathogen, the causal link with certain effects is far from obvious because the effects are either subtle or long-term:

Pathogens are often classified as relatively harmless or even commensal without sufficient long-term study to warrant such a classification. The historical record illustrates the consequences of this error. Epstein-Barr viruses and human papillomaviruses were once thought of as relatively harmless on the basis of their linkage to relatively benign diseases that occur soon after infection (infectious mononucleosis and warts respectively). But each virus can cause lethal cancers. Bacteroides was once thought to be a harmless commensal, but recent evidence indicates that it may be linked to ulcerative colitis. (Cochran et al. 2000)

Many slowly developing diseases are probably of pathogenic origin. This seems especially the case with various forms of senile dementia. The pathogen targets your brain and gains some benefit while you’re still socially and sexually active. At that stage, it’s living in a commensal relationship with you and confines its neuronal meddling to the minimum necessary. Beyond a certain age, however, it gets less benefit from you and has less incentive to keep you mentally healthy. One result may be Alzheimer's:

The possibility that Alzheimer's disease (AD) has a microbial aetiology has been proposed by several researchers. Here, we provide evidence that tissue from the central nervous system (CNS) of AD patients contain fungal cells and hyphae. Fungal material can be detected both intra- and extracellularly using specific antibodies against several fungi. Different brain regions including external frontal cortex, cerebellar hemisphere, entorhinal cortex/hippocampus and choroid plexus contain fungal material, which is absent in brain tissue from control individuals. Analysis of brain sections from ten additional AD patients reveals that all are infected with fungi. Fungal infection is also observed in blood vessels, which may explain the vascular pathology frequently detected in AD patients. Sequencing of fungal DNA extracted from frozen CNS samples identifies several fungal species. Collectively, our findings provide compelling evidence for the existence of fungal infection in the CNS from AD patients, but not in control individuals. (Pisa et al. 2015)

Alzheimer's is a late onset disease. What is the fungus doing to your brain during the long time when you’re not mentally impaired? 

Another example may be multiple sclerosis:

Many biomarkers of MS are consistent with fungal infections, such as IL-17, chitotriosidase, and antibodies against fungi. Dimethyl fumarate (DMF), first used as an industrial fungicide, was recently repurposed to reduce MS symptoms. Its mechanisms of action in MS have not been firmly established. The low risk of MS during childhood and its moderate association with herpes simplex virus type 2 suggest genital exposure to microbes (including fungi) should be investigated as a possible trigger. (Benito-Leon and Laurence 2017)

References

Benito-Leon, J. and M. Laurence. (2017). The Role of Fungi in the Etiology of Multiple Sclerosis. Frontiers in Neurology 16 October
https://www.frontiersin.org/articles/10.3389/fneur.2017.00535/full

Cochran, G.M., Ewald, P.W., and Cochran, K.D. (2000). Infectious causation of disease: an evolutionary perspective. Perspectives in Biology and Medicine 43: 406-448.
https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.182.5521&rep=rep1&type=pdf  

Hughes, D.P., J.P.M. Araujo, R.G. Loreto, L. Quevillon, C. de Bekker, and H.C. Evans. (2016). Chapter Eleven - From So Simple a Beginning: The Evolution of Behavioral Manipulation by Fungi. Advances in Genetics 94: 437-469.
https://www.sciencedirect.com/science/article/abs/pii/S0065266016300049

Pisa, D., R. Alonso, A. Rabano, and I. Rodal. (2015). Different Brain Regions are Infected with Fungi in Alzheimer's Disease. Scientific Reports 5(15015)
https://www.nature.com/articles/srep15015