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Updated: Jun 9, 2025
A Protocol to Infect Caenorhabditis elegans with Salmonella typhimurium
Published on: June 26, 2014
Esculetin Combats Multidrug-Resistant Salmonella Infection and Ameliorates Intestinal Dysfunction via the Nrf2
Wenjiao Xu1,2, Wenjun Ding2, Liyan Jia3
1Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing 100730, China.
Abstract:
The increasing incidence of multidrug-resistant (MDR) Salmonella enterica serovar Typhimurium (S. Tm), known for causing invasive enteric infections, presents a significant public health challenge. Given the diminishing efficacy of existing antibiotics, it is imperative to explore novel alternatives for the treatment of MDR S. Tm infections. Here, we identified esculetin (EST), a natural coumarin abundant in dietary foods and herbs, as a compound exhibiting broad-spectrum antibacterial properties against a range of MDR bacteria. Our findings demonstrate that EST effectively inhibited the proliferation and expansion of MDR S. Tm in both in vitro experiments and animal models. Specifically, EST significantly downregulated the type 3 secretion system-1 (T3SS-1) virulence expression of MDR S. Tm, thereby preventing its invasion into intestinal epithelial cells. In S. Tm-infected mice, we observed cecal injury characterized by the upregulation of inflammatory cytokines, a reduction in goblet cell numbers, a decreased expression of tight junction proteins, and microbial dysbiosis. Conversely, EST treatment ameliorated these pathological changes induced by S. Tm infection and reduced oxidative stress by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, thereby improving intestinal barrier function. These results suggest that dietary coumarins or a targeted plant-based diet may offer a promising strategy to counteract MDR bacteria-induced enteric diseases.
Insights
Esculetin, a natural compound, combats multidrug-resistant Salmonella Typhimurium by inhibiting its virulence and improving gut health. This dietary compound offers a promising alternative for treating resistant bacterial infections.
Area of Science:
- Microbiology
- Immunology
- Natural Product Chemistry
Background:
- Multidrug-resistant (MDR) Salmonella enterica serovar Typhimurium (S. Tm) infections pose a significant public health threat due to limited antibiotic options.
- Novel therapeutic strategies are urgently needed to combat invasive enteric infections caused by MDR pathogens.
Purpose of the Study:
- To investigate the antibacterial potential of esculetin (EST), a natural coumarin, against MDR S. Tm.
- To elucidate the mechanisms by which EST exerts its protective effects in vitro and in vivo.
Main Methods:
- In vitro antibacterial assays and in vivo studies using a mouse model of S. Tm infection.
- Analysis of bacterial virulence factors, including the type 3 secretion system-1 (T3SS-1).
- Assessment of intestinal injury, inflammatory markers, goblet cell counts, tight junction protein expression, microbial composition, and oxidative stress via Nrf2 pathway activation.
Main Results:
- Esculetin demonstrated broad-spectrum antibacterial activity and effectively inhibited MDR S. Tm proliferation in vitro and in vivo.
- EST downregulated T3SS-1 expression, reducing bacterial invasion into intestinal cells.
- EST treatment ameliorated cecal injury, reduced inflammation and oxidative stress, improved intestinal barrier function, and restored microbial balance in infected mice.
Conclusions:
- Esculetin is a promising natural compound for combating MDR S. Tm infections.
- Dietary coumarins or plant-based diets may serve as a viable strategy against MDR bacterial enteric diseases.
- Targeting bacterial virulence and host inflammatory pathways with natural compounds offers a novel therapeutic approach.
