Why Do Infections Kill? It’s Mostly Miscommunication


Killing the host means committing suicide, so why do it?

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Pathogens, like any other lifeforms, have been selected by evolution for traits of successful reproduction or replication. There are 6 types of pathogens (or infectious agents): Bacteria, viruses, fungi, protozoa (tiny parasites), helminths (larger parasites like worms), and prions (infectious proteins).

But “for these tiny invaders, a dead host is a dead end,” Madeline Drexler, editor of Harvard Public Health magazine, wrote in the book, What You Need to Know About Infectious Disease. If pathogens meet the same fate as a dead host, why do they have the capacity to kill?

New Meeting Places

One reason is “new meeting places,” Drexler said. “Humans have cleared forests for agriculture and suburbanization, leading to closer contact with environments that may harbor novel (or newly introduced) pathogens.” International and wildlife trade, climate change, and traveling all contribute to “new meeting places” of pathogens as well.

Coronaviruses co-exist in bats but kill humans, for example. Coronaviruses have evolved to withstand the strong antiviral immunity of bats. Bats are the only mammal capable of prolonged flight, which increases their internal body temperature that gives interferons — immune cells that interfere with virus replication — a boost. In humans with weaker interferon responses, coronaviruses then become pathogenic.

The same applies to most, if not all, zoonotic diseases wherein microbes become pathogenic when they ‘jump’ to a different host with a different immune system. The majority of infectious diseases affecting humans are zoonotic. Ebola, HIV, dengue, malaria, bird flu, and rabies are a few examples.

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Coincidental Evolution

This hypothesis is similar to the above of “new meeting places” wherein “virulence factors arose as a response to other selective pressures, such as predation, rather than for virulence per se,” Shuyang Sun, a postdoctoral researcher at the University of Technology Sydney, and colleagues wrote in a 2018 review titled, “Dual Role of Mechanisms Involved in Resistance to Predation by Protozoa and Virulence to Humans.”

For example, “Cryptococcus neoformans is a yeast that can cause lung infections in immunocompromised people and invades the brain by using host monocytes,” Sun and colleagues continued. Monocytes are a type of phagocytic immune cell that engulfs dead cells or microbes.

The ability of this yeast to live inside host monocytes is believed to have evolved as a defense mechanism against being eaten or engulfed by amoebas. Hence, microbes can become extremely virulent (or pathogenic) as an evolutionary adaptation to predators.

The coincidental evolution hypothesis posits that microbes that can survive engulfment by amoebas have already adapted to engulfment by phagocytes. A few such examples include Klebsiella pneumonia, Vibrio cholera, and Legionella pneumophila. Adaptation to phagocytic engulfment can vary: Some microbes can live inside it without causing any harm; some destroy it; some use it to invade other areas like the brain.

Culture Escherichia coli with a phagocytic amoeba (Dictyostelium discoideum) for several generations and a new strain eventually emerged that can kill the amoeba. Infect mice with this new strain and they suffer more lethal sepsis as a result. “Our observations support the coincidental hypothesis for the evolution of virulence: the capacity to resist grazing by protozoa [in natural habitat] manifests itself in a human host as increasing virulence,” the study authors concluded.

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Host Immune System Overreaction

“As [the host] tries to figure out how to adjust to an invasion from something completely new, the immune system overreacts. This is what makes the host sick,” said Misha Ketchell, an editor of The Conversation. “It usually isn’t an advantage for the virus to make people sick; it is an accident of the hosts’ immune system overreacting to something it doesn’t recognize.”

Ketchell reinforces the above point, that “a dead host is a dead end,” so killing or sickening the host too much doesn't necessarily favor the pathogen survival or transmission. Instead, it is often an overdriven immune system that releases too many inflammatory cytokines — the cytokine storm—that kills.

Cytokines serve to power immune cells to eliminate pathogens but they harm nearby healthy cells in the process. Cytokine storms, thus, cause widespread cell damage and multi-organ failure. Virulent microbes like the Ebola virus and SARS-CoV-2 mainly kills the host this way.

Cytokine storms can be unpredictable as an individual’s immune reactions to a pathogen differ, owing to a combination of genetic, environmental, and lifestyle factors. A specific genotype can prime one’s immune system to react especially strongly to a specific pathogen, for example. Previous infections (an environment factor) with HIV, herpes virus, bacteria, fungi, or parasites can sometimes make the immune system more sensitive to overreaction. Poor diet or sedentary behavior weakens the regulatory efficacy of the immune system and promotes chronic, low-grade inflammation. These factors then culminate in the event of cytokine storms.

It’s Mostly Miscommunication

For microbes, “a dead host is a dead end.” Killing the host means committing suicide. That’s why most pathogens just sickened the host enough for transmission purposes via coughing or fecal matter, for example. Only a relatively few pathogens kill their host, and this is often accidental, as a result of evolutionary or physiological miscommunication.

Evolutionary miscommunication is like how microbes adapted to bats with a stronger immune system or amoebas engulfment becomes too virulent (or pathogenic) in a different host. Physiological miscommunication is like how the host immune system reacts poorly (in an unregulated manner) to a foreign microbial entity.

This article was originally published in Microbial Instincts with minor modifications.

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