Salmonella typhimurium. Credit: Rocky Mountain Laboratories, NIAID, NIH
Salmonella typhimurium. Credit: Rocky Mountain Laboratories, NIAID, NIH

When Our Microbes Chat, Dangerous Germs Are Eavesdropping

In Africa, a superb starling has just spotted an eagle and gives off an alarm call. Any starling within earshot goes on high alert, but so do nearby vervet monkeys. They have learned to eavesdrop on the starling’s calls to gain extra intelligence about incoming threats.

They’re not alone. Mongooses listen in on the calls of hornbills, black-capped chickadees act as inadvertent sentries for up to 50 species of birds, and lemurs tune into the soundtracks produced by forest birds. Eavesdroppers, it seems, are everywhere. They’re even found inside your bowels.

Your guts are home to tens of trillions of microbes, which help to digest your food, control your immune system, and protect you from invasions by disease-causing germs. They also communicate with each other, but through chemicals rather than sound.

For example, when threatened by antibiotics, the gut bacteria Escherichia coli release a substance called indole, which toughens them up. It prompts them to mass-produce molecular pumps that can evict any drugs that get inside them. They start building slimy cities called biofilms to fortify themselves against incoming antibiotics. And perhaps most importantly, some of them enter a dormant, inactive state. Since all of our antibiotics are designed to kill growing bacteria, these sleeper cells slip right under their radar. They’re called  persisters, are they’re extremely hard to kill.

Nicole Vega from Boston University discovered the link between indole and persistence last year. Now, she has shown that another bacterium—Salmonella typhimurium, a major cause of food-related illness—can eavesdrop on E.coli’s indole signals.

It doesn’t make any indole of its own, but it responds to the chemical in the same way as E.coli. Vega, with help from Amanda Samuels, showed that S.typhimurium becomes over three times more tolerant of certain antibiotics when grown alongside E.coli. And they only gained this advantage when Vega seeded the cultures with tryptophan—the substance that E.coli needs to make indole.

These experiments were done in glass flasks, but the team also challenged the bacteria in a more realistic environment—the guts of a nematode worm. Vega loaded the worms with S.typhimurium, and either normal E.coli or a mutant strain that couldn’t make indole. When she then added an antibiotic, she found that S.typhimurium tolerated the drug more easily if it sat alongside indole-making E.coli, rather than the mutant strain.

Like the vervets and lemurs, S.typhimurium intercepts signals used by a different species to ensure its own survival. Such eavesdropping might be very common. Indole is a widespread signal among bacteria, and might help different species to communicate with each other. Indeed, both E.coli and S.typhimurium do so by activating the same set of genes, which suggest that even species that have lost the ability to make indole have kept the machinery they need to respond to it. And that could spell trouble for us, allowing harmful bacteria to fortify themselves against our medicines by listening in on the chemical chatter of our microbial allies.

Reference: Vega, Allison, Samuels, Klempnerd & Collins. 2013. Salmonella typhimurium intercepts Escherichia coli signaling to enhance antibiotic tolerance. PNAS