Andy Dubbin/Fusion

Trillions of Tiny Microbes, All Over You

Meet Bacteria.

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You should be well acquainted by now. After all, 90% of cells in the human body are single-celled microbes, and the ratio of bacterial to human DNA is 100 to 1.

A blunter way of stating that? As molecular biologist Bonnie Bassler deadpans in a Ted Talk on "How Bacteria 'Talk'"—"I know you think of yourself as human beings, but I think of you as 90 or 99 percent bacterial."

DON'T PANIC (YET)

We've known for a long time that bacteria are virtually everywhere and exert tremendous influence over the natural world.

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And while that ubiquity is intimidating, we also know that bacteria aren't all bad. Beneficial "probiotic" microorganisms also proliferate and promote mutually beneficial conditions in their eukaryotic hosts.

Still, only in the last decade or so have we begun to grasp the group mechanics and chemical pathways that bacteria depend on to take any action in the first place.

Bacterial Status Updates

In "quorum sensing" (or "QS" for short), bacteria use chemical signals to determine the components of their environment, assess their local population, and activate group behaviors.

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Observing the mechanics of QS has allowed scientists to begin subverting the molecular process of bacterial communication.

Helen Blackwell is an organic chemist and 2014 Blavatnik Award finalist who works to identify the signaling molecules bacteria use to communicate and experiment with the chemical pathways that drive QS.

"[Quorum sensing] is intrinsically a chemical process," Blackwell explains. "If you can tinker with those [signaling] molecules, you can have a really significant effect on the quorum sensing outcomes."

In one anti-infective therapy, Blackwell's lab designed, synthesized, and tested a variety of chemical analogs for autoinducing peptides (AIPs) to examine how variations in the structure of signaling molecules can activate or inhibit receptor activity in Staphylococcus aureus, a pathogen known for onsetting life-threatening disease states.

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These chemical analogs are compelling tools for measuring outcomes in host-bacterial interactions.

Eukaryotic hosts can intercept QS communications—In one experiment with the common annual flowering plant A. thaliana, they will respond to known signaling molecules even in the absence of bacteria.

Experimental modifications of another typical chemical signaling molecule, N-Acyl homoserine lactones (AHLs)—known autoinducers complicit in US signaling in many Gram-negative bacteria, demonstrates the impact that tiny, synthetic agents can have on bacterial virulence attacks in actual eukaryotic hosts (read: potatoes).

Fight La Résistance

One of the most promising aspects of QS research is that, unlike a problem facing antibiotic treatments, bacteria should not develop resistance to QS-regulating agents like AHLs and AIPs—at least, not as quickly.

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And this makes sense—QS therapies don't risk creating resistant bacterial populations because they don't kill bacteria—like bacterial gangbusters, they just prevent them from working together.

Because it's not advantageous for bacteria to develop resistance to quorum sensing molecules, Blackwell explains, "you have a much longer lifetime for these agents."

"[Some bacteria] will eventually get resistance to quorum sensing inhibitors—we’ve found those in our lab," Blackwell explains, "but those resistant bacteria don’t overtake the population. And that’s key."

Into The Wild

Naturally, one major goal in microbiology is the development of therapeutics to target specific diseases. But before QS can take us there, it must meet intermediary goals, such as explaining the role of quorum sensing in interspecies environments, and in complex mixed-microbial communities like those in the soil around plants, in the GI tract, or a microbial mat.

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"The idea that there are other bacteria around them that allow them to sense their niche—we assume it, but that idea is hotly debated." Blackwell explains QS research still has hurdles to overcome, "showing this definitively in a biologically relevant environment has never been done. That motivates us."

Dr. Rob Knight, another 2014 Blavatnik Award Finalist, has spearheaded research on a particular microbiome with tremendous potential for Quorum Sensing-related research: the human gut.

Knight founded "The American Gut" project to identify and sequence all manner of North American scum, and he has long-term plans to sequence all microbes on Planet Earth.

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Knight points out that our capability to culture bacteria from the gut—that is, grow them in a lab to be able to study their unique respective signaling pathways—is limited to 5-15% using traditional techniques, and 60-80% by means which physically isolate bacteria down to a single cell—not what a microbiologist would call a "biologically relevant environment."

That limits our ability to characterize all consortia of bacteria, but Knight says "It might be possible to get even more [bacterial cultures] to grow by manipulating quorum sensing."

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While Blackwell faces the limitation of the "unculturable" in bacterical networks residing in us, on us, and all around us, she agrees quorum sensing tools may hold the key to the unknown.

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"A big problem in microbiology is that we’ve only cultured less than 1% of the bacteria here on Earth," she explains, "but if we can generate agents to act as chemical tools to trick bacteria into thinking they’re among friends…that could be very exciting."

If you're interested in learning more about the study of bacterial networks, check out the American Society for Microbiology's 5th annual conference on cell-to-cell communication in bacteria in October.

Andy is a graphics editor and cartoonist at Fusion.