# A Colombian strain of Clostridioides difficile ribotype 002 induces a highly inflammatory response in a mouse infection model

## TL;DR

A Colombian strain of Clostridioides difficile (RT002) causes a strong inflammatory response in mice, similar to a known hypervirulent strain.

## Contribution

The study identifies RT002 as a highly inflammatory C. difficile strain prevalent in Colombia.

## Key findings

- RT002-infected mice showed higher bacterial load and immune cell levels compared to other strains.
- RT002 induced elevated cytokine levels like RANTES, eotaxin, and MCP-1.
- Histopathology showed RT002 caused colonic inflammation similar to the hypervirulent RT027 strain.

## Abstract

Clostridioides difficile causes diarrhea associated with antibiotic use in hospitalized patients. Recent studies have identified that C. difficile ribotypes RT002, RT106, and RT591 as the most prevalent circulating strains in Colombia; thus, we aimed to assess the capability of these ribotypes to elicit an inflammatory response during in vivo infection. To achieve this, C57BL/6 mice were treated with cefoperazone (CPZ) for 5 d to develop C. difficile infection (CDI) model. Two days post-antibiotic treatment, the mice were orally inoculated with 1 × 105 spores of C. difficile strains belonging to ribotypes RT002, RT106, RT591, and RT027 (ATCC strain, used as control). A group of animals was euthanized on day 7 post-infection to determine the bacterial load, total leukocyte number, and chemokines/cytokines levels in situ, and for histopathological analysis. RT002-infected groups showed significantly higher bacterial load, CD45+ leukocytes, and RANTES, eotaxin, MCP-1, G-CSF, and IL-2 levels compared to the other groups, suggesting a robust immune response. Furthermore, histopathological analysis of colonic tissue from the group infected with RT002 revealed the presence of an inflammatory response similar to the hypervirulent strain RT027. These results suggest that RT002 of C. difficile, one of the main circulating strains in Colombia, can induce a severe inflammatory response, potentially correlating with increased virulence and severity of these strains in CDI cases.