PULLMAN, Wash. -- Bacteria that cause intestinal infections typically avoid a stinky chemical — one that can kill them at high enough concentrations — inside human intestines, but they may actually swim toward it when a hearty meal is the reward.
"Imagine you've made a long journey and you're starving," said Arden Baylink, assistant professor. "You look for a place to eat, only to find it crowded with others and a line out the door. To make things worse, the crowd is hostile and pretty stinky. You face a dilemma: Is it worth staying to eat or should you leave?"
This is the problem faced by disease-causing bacteria like Salmonella as they navigate our digestive tracts, according to new research from the Baylink Lab at Washington State University. The study, published in eLife , sheds light on how pathogenic bacteria make these kinds of decisions and could eventually help scientists create new medicines to prevent and treat intestinal infections.
The bacterial "stink" is a chemical called indole, which helps give feces its distinctive odor. It is produced by beneficial bacteria known as microbiota that live in the gut and can kill infectious bacteria when it reaches high enough levels.
Baylink and Kailie Franco, a doctoral candidate in the Baylink Lab, set out to understand this phenomenon using a custom-built microscope designed to record videos of swimming bacteria. Pathogens have a built-in navigation system called chemotaxis, which works like a bacterial sense of smell, allowing them to swim toward nutrients and away from chemicals that can harm them, like indole.
Earlier studies showed that the bacterium Escherichia coli uses chemotaxis to swim away from indole, leading scientists to think this might be one way microbiota protect humans — by releasing indole that repels pathogens. Previous studies, however, tested only pure indole, not indole mixed with the nutrients present in the intestines, which more accurately reflects the conditions in the gut.
Baylink and Franco simulated the intestinal environment by combining nutrients that bacteria rely on for survival, such as amino acids and sugars, with varying concentrations of indole. Using their specialized microscope, they recorded videos of bacteria to observe how they responded to these mixtures.
"At first, we saw what others had seen. Salmonella swims away from pure indole, no question, and really fast. Within 10 seconds, the bacteria are gone," Baylink said.
But that changed when indole was combined with nutrients and the bacteria were attracted.
The degree to which bacteria were attracted to nutrients depended on how much indole was present. Less indole meant a stronger attraction, but even at high levels, the bacteria were always at least somewhat attracted and never repelled.
This pattern held across multiple pathogens, including different types of Salmonella enterica, Escherichia coli, Citrobacter koseri, and Enterobacter cloacae, bacteria that can cause life-threatening intestinal infections and are posing challenges for doctors because of the rise of antibiotic resistance.
The team also tested whether indole prevented Salmonella from infecting intestinal tissue but found it did not.
The study reveals a new way to think about how bacteria infect and cause disease in the gut. Indole isn't just something bacteria avoid — it's information.
"Indole tells them where their competition, the microbiota, is located. Bacteria can use that to swim to regions where competition is less fierce and nutrients are plentiful," Baylink said.
The research was funded by the NIH's National Institute of Allergy and Infectious Diseases and included collaborators at the University of Oregon, Michael J. Harms, Zealon Gentry-Lear, and Michael Shavlik.
The research could eventually lead to new treatments for drug-resistant bacterial infections and sepsis by blocking how bacteria sense their environment. "We're grateful to the taxpayers who support our research so we can advance our understanding of bacterial diseases and develop new treatments," Baylink said.
