Researchers have uncovered a new bioelectrical mechanism that allows pathogens such as Salmonella to locate entry points in the gut lining, enabling them to invade and cause infections.
What allows harmful bacteria to find ways into the body for infections?
This is a crucial question for experts in infectious diseases and microbiology. Pathogens like Salmonella navigate the intricacies of the gut, where beneficial microbes and immune cells vastly outnumber them. Yet, they manage to seek out vulnerable areas in the gut that facilitate their entry into the body.
A team of researchers from UC Davis Health has identified a unique bioelectrical mechanism that these pathogens utilize to locate these openings. Their findings were published today in Nature Microbiology.
Pathogens breaching the gut barriers
Each year in the United States, Salmonella leads to approximately 1.35 million illnesses and 420 fatalities. To infect an individual, this pathogen must breach the gut lining.
“After ingestion, Salmonella reaches the intestines, where they contend with more than 100 trillion helpful bacteria (known as commensals). The odds they face are one in a million!” remarked Yao-Hui Sun, the lead author of the study and a research scientist associated with the Departments of Internal Medicine, Ophthalmology and Vision Science, and Dermatology.
To explore how Salmonella navigate within the intestines, the researchers monitored the movements of S. Typhimurium (a Salmonella strain) and compared it to a harmless strain of E. coli.
Understanding the intricate gut environment
The structure of the intestine is highly complex, featuring villus epithelium and follicle-associated epithelium (FAE). The villus epithelium consists of absorptive cells (enterocytes) with protrusions that enhance nutrient absorption.
Conversely, FAE contains M cells that lie over small groups of lymphatic tissue called Peyer’s patches. These M cells are responsible for sampling antigens, acting as the immune system’s frontline against microbial and dietary substances.
Research outcomes
In experiments using a mouse model, it was observed that Salmonella detect electric signals in the FAE. They migrate toward this section of the gut, identifying openings to enter. This movement in response to electric fields is referred to as galvanotaxis or electrotaxis.
“Our research revealed that this ‘entry point’ has electric fields that Salmonella exploit to pass through,” stated the study’s senior author Min Zhao, a UC Davis professor of ophthalmology and dermatology, along with being a researcher at the Institute for Regenerative Cures.
The findings also demonstrated that E. coli and Salmonella react differently to bioelectric fields, exhibiting opposing responses to the same electrical cue. While E. coli congregate next to the villi, Salmonella are drawn towards the FAE.
The study detected electrical currents circulating through the gut, entering the absorptive villi and exiting via the FAE.
“Importantly, the bioelectric field in the gut epithelial provides conditions that Salmonella exploit for localization to the FAE, which is less favorable for E. coli,” explained Sun. “It appears that Salmonella favors the FAE as a gateway for invading the host and triggering infections.”
Previous research suggested that bacteria use chemotaxis to navigate. Chemotaxis involves bacteria sensing chemical gradients to move toward or away from certain substances. However, this new study indicates that the galvanotaxis of Salmonella toward the FAE does not occur through typical chemotaxis pathways.
“Our findings present an alternative or additional mechanism for how Salmonella target the gut epithelium,” Zhao noted.
Possible connections to IBD and other intestinal disorders
This research may shed light on complex chronic illnesses, such as inflammatory bowel disease (IBD).
“This mechanism exemplifies a new type of ‘arms race’ between pathogens and the human body, with potential implications for other bacterial infections and avenues for prevention and treatment,” Zhao remarked. “IBD is believed to stem from an excessive and abnormal immune response to beneficial bacteria. It will be intriguing to determine if patients prone to IBD exhibit irregular bioelectric activity in their gut epithelium.”
Co-authors from UC Davis Health on the study include Fernando Ferreira, Brian Reid, Kan Zhu, Li Ma, Briana M. Young, and Renée M. Tsolis. Additional co-authors are Catherine E. Hagan and Alex Mogilner.
