Why (Microbial) Memory Matters
In the human brain, memories-little nuggets of past information-help people navigate their current situations and circumstances. Typing on a computer, knowing the route home from work, choosing not to drink weird-smelling milk after that 1 bad experience…all are rooted in memory.
But the act of remembering is not an exclusively brainy endeavor. It also takes place at the cellular level. "Memory is simply storage and retrieval of information. If that is the simplest definition that you can work [with], that means any system can have memory," said Souvik Bhattacharyya, Ph.D., an assistant professor at the UTHealth Houston whose new lab focuses on microbial ecology. For instance, adaptive immune cells draw from prior exposure to a pathogen to elicit a quicker and more robust response the next time they encounter it.
Microbial cells, like bacteria and yeast, similarly exhibit forms of so-called history-dependent behavior that boost their survival. They must constantly adjust to fluctuations in their environment. By "remembering" a past change (e.g., a switch to a new nutrient source), microbes and microbial populations can alter their behavior and adapt more quickly upon re-exposure to a condition, compared to if they hadn't been exposed to the condition at all.
Moreover, because microbes largely replicate via cellular division, "memory can get passed on to the next generation as well," Bhattacharyya explained. "So that's the added feature of microbial memory that is different from multicellular organisms."
The development of a memory response can save microbes energy, as they capitalize on previous transcriptional and metabolic efforts to respond to shifts in their surroundings. On a population level, having some cells poised for a given environmental change diversifies the phenotypic pool to ensure optimal survival in what may be non-optimal conditions.
How Do Microbes Remember?
Microbial memory is not like cognitive memory, which relies on the collective activation, modification and reactivation of groups of neurons in response to stimuli. The stimulus may change, but the brain uses this same basic pathway to create and recall memories.
In microbes, the mechanistic basis of memory varies depending on the microbe and stimulus, with "memory" itself referring to a range of behaviors, like changes in motility or growth dynamics, that last from a few seconds to several generations. "Information can be stored in metabolites, nutrients, proteins and modifications in proteins or DNA," noted Bhattacharyya.
Epigenetic Changes
In some cases, past experiences are recorded as changes in gene expression. For example, if the yeast Saccharomyces cerevisiae (brewer's yeast) is switched from an environment rich in glucose to one steeped in galactose-a less-preferred sugar that's similar to glucose with a few molecular tweaks-it takes time for their galactose-utilization genes to kick into gear. However, the switch elicits epigenetic changes (i.e., modification in chromatin structure) that ensure those genes are rapidly reactivated upon re-exposure to galactose. This galactose memory response will last for 7-8 cellular divisions. Scientists postulate that epigenetic memory allows microbes to meet the moment without permanently altering their physiology, as would occur in the event of DNA mutation.
Protein Buildup
There are also instances where memories consist of proteins that build up in a cell after exposure to a stressor or stimulus. Those proteins-released in response to the initial trigger-can stick around and prepare the organism should they encounter the trigger again. As cells divide (or undergo phenotypic transformations, like sporulation) their progeny inherits the protein leftovers and is, thus, equipped to manage a stress they "remember" but have never seen themselves. The memories fade as proteins break down or are diluted out through natural division.
Nutritional Memory
Nutrients form additional fodder for memories. Bhattacharyya and his colleagues recently uncovered a memory response in Escherichia coli that slots into this category. They found that E. coli cells with a prior experience of swarming (when bacteria use their flagella to migrate as a group across a surface) swarm more efficiently when they encounter a new surface compared to those with a swarm-less past. How do they do it?
"They basically change the levels of iron within the cell," Bhattacharyya explained. That is, the memory of swarming is stored in the form of cellular iron concentrations. "So, more iron within the cells means less motility on the surface, and less iron means they will move [swarm] more." Because iron is imperative for survival, low iron concentrations may incentivize cells to get moving and find more of the nutrient. Iron memory and its associated swarming potential is heritable-mother cells pass it onto their daughter cells for up to 4 generations.
Bhattacharyya highlighted that there is more to learn about the mechanism underlying this phenomenon. It appears to be less specific than other forms of microbial memory, with the ability to store information related to more than just swarming, including antibiotic tolerance. Because nutrients are crucial for so many organisms, there may also be versions of iron memory in other life forms (e.g., eukaryotes) too, not just bacteria. "Iron is ubiquitous, [so] maybe this kind of memory mechanism is a common way to store information," Bhattacharyya said.
It's worth noting that the above examples represent a fraction of the ways microbes remember. New memory mechanisms are still being discovered in diverse organisms.
Harnessing Microbial Memories
The memory capacity of microbes is not just something to be studied in a lab; it could have important implications for human and environmental health. "Let's say you treat an infection with an antibiotic. Then some of the [bacterial] population can remember it had encountered that antibiotic and becomes transiently resistant to it," Bhattacharyya said, with a shrug and a "you-guess-the-outcome" expression. "There are previous reports that hint towards that, although it's not known how [the cells] do it," he continued. Memory responses could play a role-his team's work on iron memory points to ties to antibiotic tolerance. Memory also facilitates efficient host adaptation, biofilm formation and the ability to withstand a slew of stressors.
With that in mind, can we use the memories of microbes in practical ways? There are many cases where synthetic memory circuits are programmed into organisms. Such programming may involve altering the DNA or enzymatic machinery of microbes, so that there is a discernible change in response to specific conditions within the environment or within a host. The change can then be detected by scientists for various analytical or even diagnostic purposes.
The natural memory systems of microbes, however, remain largely untapped.
For Bhattacharyya, targeting microbial memory requires first getting a better handle on how it works. There are an astounding array of environments and conditions microbes can encounter. Understanding if, and how, memory facilitates survival in that expansive pool of possibilities is a research priority. Furthermore, "much longer forms of naturally occurring memory in clinically relevant bacteria has yet to be shown," he said. Microbes' ability to remember after a couple of hours is impressive. But what about organisms that grow slowly? "Mycobacteria have a 1-day doubling time. Would they [then] have 7 or 8 days of memory? That would be very interesting to know."
The more scientists learn, the greater the likelihood that all these questions will eventually become nothing more than, well, a memory.
Microbial memory may play a role in antimicrobial resistance (AMR). Check out our resource page for the latest insights how AMR develops and what is being done to combat it.
