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How Bacterial Spores Calculate the Best Time To Return to Life

A hand holding an abacus made of bacterial spores, counting stimuli needed for germination.
Credit: Anne Hashimoto
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A new study by researchers at the University of California, San Diego has found that dormant forms of bacteria called spores can assess their environment over time and determine when it is favorable to “wake up”. The findings are published in Science.

Dormancy as a survival mechanism

During difficult periods for survival, bacteria can turn themselves into spores during a process called sporulation. They become dormant, slowing their biological processes to a halt and growing a thick outer protective coating, allowing them to wait out periods of starvation or stress until conditions become more favorable. Spores are capable of enduring intense heat, radiation and damage by chemical agents – while some have even survived simulated space travel to Mars.

Anthrax is a notable example of a spore-forming bacterium, infamously used as a bioweapon in the 2001 anthrax attacks which saw spore-filled letters mailed to several news outlets and politicians, killing 5 people and infecting 17 others.

Spores go through several stages when they revive and become active again. During the germination phase, spores rehydrate and disassemble their protective coating. They then go through an outgrowth phase where they elongate and restart all their cellular machinery and begin producing new molecules again. However, scientists have been unsure how exactly spores monitor their environment during their dormancy and make sure that they “wake up” at the right time.

The researchers in the current study explored the possibility that during their dormancy, spores can undergo physiological changes in response to subtle signals that on their own aren’t enough to trigger germination and integrate this information over time.

Keeping score with potassium

The researchers analyzed thousands of dormant spores of the bacterium Bacillus subtilis to see if they could detect small pulses of signals that can trigger germination. They used three-minute pulses of the naturally occurring amino acid L-alanine which spores are known to have receptors for.

Around 5% of spores germinated after a single pulse, and approximately half of the remaining spores germinated after a second pulse. Therefore, the researchers suggested that these signals move the spores closer to a so-called “germination threshold”. The spores are sensitized by the first pulse, leading them to germinate once they receive enough signals to reach the threshold.

But how are spores capable of monitoring these signals as they lay dormant? The researchers developed a mathematical model, proposing that the spores use passive movement or “flux” of intracellular ions. This would allow them to integrate information on favorable stimuli as they lay dormant, and not use up valuable cellular energy. The researchers focused on potassium, an abundant ion in bacteria that is also linked to stress responses in B. subtilis.

Experimental data supported this model, showing that cells respond to pulses of favorable signals by releasing stored potassium ions. With each release of potassium, the effect of the favorable signals accumulates until the potassium concentration decreases enough to reach the germination threshold. The researchers suggest that this mechanism is not too dissimilar to the action potentials involved in the firing of nerve cells.

Video of a dormant spore performing signal integration. Credit: Süel Lab

“In both bacteria and neurons, small and short inputs are added up over time to determine if a threshold is reached. Upon reaching the threshold, spores initiate their return to life, while neurons fire an action potential to communicate with other neurons,” Professor Gürol Süel, senior author of the study, explained in a press release.

Reframing our knowledge of dormancy

This proposed “integrate-and-fire” mechanism shows how spores can remain inactive while still responding to signals from their environment. The findings shed new light on our idea of cellular dormancy, and the researchers suggest they may reframe our understanding of life in extreme conditions on Earth and even on other planets.

“This work suggests alternate ways to cope with the potential threat posed by pathogenic spores and has implications for what to expect from extraterrestrial life,” Süel elaborated. “If scientists find life on Mars or Venus, it is likely to be in a dormant state and we now know that a life form that appears to be completely inert may still be capable of thinking about its next steps.”

Reference: Kikuchi K, Galera-Laporta L, Weatherwax C, et al. Electrochemical potential enables dormant spores to integrate environmental signals. Science. 2022;378(6615):43-49. doi: 10.1126/science.abl7484