Colonizing the stomach: How do cancer-causing bacteria navigate?

Helicobacter pylori (H. pylori) have colonized the stomachs of billions of people worldwide. Once an H. pylori infection occurs, it is challenging to eradicate. This is a significant biomedical problem as H. pylori can promote stomach ulcers and gastric cancers. How H. pylori navigate and colonize specific niches in the stomach remains largely unknown. Addressing this gap in fundamental knowledge is crucial for preventing infections moving forward.

Pushkar Lele, associate professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University, recently received an R01 research grant from the National Institute of General Medical Sciences totaling more than $1.3 million to investigate the mechanisms that enable H. pylori to navigate with the aid of motility appendages called the flagella. To do this work, his group will combine experimental techniques such as optical trapping and Förster resonance energy transfer (FRET) with computational modeling. 

Inside a bacterium, rapid signaling reactions constantly occur to control its movements. Measuring these reactions is the key to understanding H. pylori’s navigational strategies. However, such measurements are incredibly difficult inside a bacterium considering its minuscule size — a couple of microns – and the speed at which it moves – almost 30 times its length per second.

Lele’s group proposes to overcome the challenge by manipulating single bacterial cells through the power of light. Using what is known as an optical trap, the researchers will catch hold of single H. pylori cells and release them at distinct separations from their chemical targets to observe their navigational strategies. They will develop FRET assays to visualize signaling interactions in these cells.

“Bacteria rely on numerous signaling mechanisms to adapt their behavior to environmental conditions,” said Lele. “The pathway we are interested in specifically helps them migrate from an unfavorable location to a favorable environment — a process known as chemotaxis. How do H. pylori sense and respond to environmental cues despite appearing to lack key enzymes in their arsenal? There has never been a more opportune time to tackle these important questions in collaboration with renowned research groups in the field.”