# RegIIIβ promotes Salmonella Typhimurium colonization of the gut in the early-stage gastrointestinal infection by enhancing flagella-driven locomotion

## TL;DR

RegIIIβ, an antimicrobial protein, unexpectedly helps Salmonella move and infect the gut, challenging traditional views of immune defense.

## Contribution

Discovers RegIIIβ's novel role in promoting Salmonella motility and gut colonization despite its bactericidal reputation.

## Key findings

- RegIIIβ binds to Salmonella and increases its locomotion speed by maintaining membrane potential.
- Salmonella exploits RegIIIβ to enhance gut colonization and infection in early stages.
- Salmonella has evolved tolerance to RegIIIβ and uses it to improve flagellar-based movement.

## Abstract

The bactericidal lectin RegIIIβ secreted by intestinal epithelial cells, kills the microbiota and enteropathogens but also been suggested to modulate bacterial physiology and host interactions. However, it remains to be determined whether RegIIIβ plays roles beyond its bactericidal effects. The present study revealed that RegIIIβ binds to the enteropathogen Salmonella enterica serovar Typhimurium in the gut, thereby increasing the locomotion speed of this bacterium through maintenance of the membrane potential. This led to enhanced invasion by S. Typhimurium into epithelial cells. Finally, RegIIIβ facilitated the gut colonization levels of S. Typhimurium and enteropathy in the early stages of gastrointestinal infection. In conclusion, S. Typhimurium has become tolerant to RegIIIβ in the evolutionary process, during which the pathogen has simultaneously acquired the ability to exploit this antimicrobial to enhance flagellar-based locomotion for successful gastrointestinal infection. Our findings provide novel insight into the roles of RegIIIβ in gastrointestinal infection caused by S. Typhimurium.

Foodborne diseases caused by contamination of food and water with enteropathogens, including Salmonella, can be severe, especially for young children and patients with weakened immunity. Thus, Salmonella infection accompanied by diarrhea is a major global public health concern; however, the prevention and regulation of Salmonella infections have had limited success. In contrast, we have evolved immune-defense mechanisms that protect us from such infections by producing antimicrobial proteins such as defensins and C-type lectins of the RegIII family, which can kill or inactivate enteropathogens. This study aims to explore the role of RegIIIβ, a C-type lectin, in Salmonella infections. Our findings reveal the unexpected role of RegIIIβ in enhancing the infectivity of Salmonella. Despite its known bactericidal properties, RegIIIβ does not kill Salmonella but instead binds to it, promoting its motility and colonization in the gut. These findings challenge the traditional understanding of immune defense mechanisms and open new avenues for developing strategies to combat Salmonella infections.