Gut Pathogen Swims to Avoid Host Control

Diverse communities of microbes live within the gut of humans and other animals. While most microbial residents are beneficial, occasionally even friendly bacteria can dodge the host’s control and cause disease. Research in Zebrafish published in PLOS Biology on March 20, 2020 reveals that one bacterium, called Vibrio chlorae, invades the lining of the intestine by swimming. Bacteria lacking the ability to swim were purged from the intestine, suggesting a new way to treat inflammatory diseases of the gut.

Scientists from the University of Oregon had previously found that Vibrio escapes the zebrafish’s control and colonizes the gut more than any other bacteria. “We noticed early on that this peculiar Vibrio strain also displayed vigorous swimming motility within the gut, whereas most other zebrafish gut bacteria appeared to live as non-motile multicellular aggregates,” Travis Wiles, the lead author of the paper, said.

In their new study, the scientists created mutant Vibrio that lacked the ability to swim. Using a live cell imaging technique with single-cell resolution, the movement of both mutant and motile Vibrio was monitored in real time in the zebrafish gut

Motility was previously believed to help bacteria enhance growth, but the scientists found that Vibrio mutants lacking the ability to swim had the same growth rate as motile Vibrio. Motile Vibrio, however, were able to colonize and persist within the gut, but non-motile Vibrio clumped together in the intestinal lumen and were eliminated from the gut.

The scientists also created a Vibrio strain with a genetic switch that allowed them to turn the swimming behaviour off and on within the zebrafish. “One thing I find interesting is that motility behaviors can be manipulated, and that changes in these behaviors lead to rapid changes in bacterial spatial organization and host inflammation,” Wiles said.

The zebrafish responded to the swimming behaviour by increasing production of a molecule called TNF-alpha. TNF-alpha is produced in response to acute inflammation and has been implicated in a variety of inflammatory diseases. Zebrafish infected with non-motile, mutant Vibrio did not have elevated levels of TNF-alpha.

The findings “highlight a new path to therapeutically manipulating gut bacterial populations–one that does not target growth, but the behavior and spatial organization of populations,” Wiles said.