Imagine you’re thrown into wild ocean waters, battered by waves until you can’t tell which way is up. Your only chance of survival is to somehow sense the location of a rock outcropping and cling to it. Now factor in that the churning water is highly acidic and lethal – that’s the predicament facing Helicobacter pylori, a bacterium that makes its home in one out of every two human stomachs and, for an unfortunate 20 percent of its hosts, causes ulcers.
H. pylori’s safe haven is our stomach’s lining with its protective mucus and nutrient-rich cells. New research from the lab of Stanford microbiologist Manuel Amieva, MD, PhD, published today in Cell Host & Microbe demonstrates that the bacteria are able to detect and home in on metabolic molecules released by human stomach cells. The behavior, captured in the video above, shows H. pylori swarming to a microscopic needle releasing either a solution collected from stomach cells or the molecule urea.
The corkscrew-shaped bacterium moves with the help of its tail-like flagella. The bundle of flagella spin in one direction to propel the bacteria forward. When they reverse the spin, said Amieva, the flagella become like helicopter blades, pulling H. pylori backwards.
Previous experiments have shown the bacteria swim away from acid and H. pylori is known to have four chemical sensing receptors. “But this is the first time we’ve observed in real time the bacteria swimming towards something,” said graduate student and lead author, Julie Huang, referring to the technique that allowed the lab to watch H. pylori’s swimming behavior directly.
Huang collected nutrient broth exposed to lab-grown stomach cells and loaded it in a microinjection system normally used to pierce cell membranes. The needle’s precision allowed Huang to release extremely small amounts of liquid and observe the bacteria through a microscope.
“We didn’t really think it would work,” Huang said about the first time she set up the system, “but within seconds, the bacteria detected the host media.” She recorded H. pylori swarming around the needle and later used software to analyze their motion.
She then identified urea, a molecule released by stomach cells to get rid of excess nitrogen, as the main attractant released by the microinjector. H. pylori was extremely sensitive to urea, detecting concentrations as low as 3 molecules of urea per billion water molecules. Such sensitivity may seem redundant given that urea levels in the stomach are orders of magnitude – up to 100,000 times – greater.
In fact, H. pylori is dependent on these high urea levels. It uses an enzyme, called urease, to break urea down into ammonia and bicarbonate, which then act as a chemical sponge, soaking up acidic hydrogen ions and neutralizing the stomach juices. It’s this reaction that allows H. pylori, which isn’t resistant to acid, to withstand stomach secretions for brief periods of time.
The researchers believe that urease breaks down the majority of the urea around and in the bacteria, allowing H. pylori to sense small gradient differences in urea and home in on the cells secreting it. When they deleted the bacterial gene for urease, the mutant H. pylori didn’t swarm towards urea.
It’s a tightly controlled and highly optimized system H. pylori has evolved to survive the dangerous seas of our stomachs.
Kim Smuga-Otto is a student in UC Santa Cruz’s science communication program and a writing intern in the medical school’s Office of Communication and Public Affairs.
Previously: Ulcer-causing bacteria manipulate stomach stem cells to their own ends and Researchers identify potential drug target in ulcer bug that infects half the worlds population
Video by Julie Huang/Manuel Amieva