Fisetin inhibits Salmonella Typhimurium type III secretion system regulator HilD and reduces pathology in vivo

Salmonella spp. remains a major worldwide health concern that causes significant morbidity and mortality in both humans and animals. The spread of antimicrobial resistant strains has declined the efficacy of conventional chemotherapy. Thus, novel anti-infection drugs or strategies are needed. Anti-v...

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Bibliographic Details
Published in:Microbiology spectrum 2024-01, Vol.12 (1), p.e0240623-e0240623
Main Authors: Li, Siqi, Liu, Hongtao, Shu, Jingyan, Li, Quanshun, Liu, Yuan, Feng, Haihua, Wang, Jianfeng, Deng, Xuming, Zhang, Yong, Guo, Zhimin, Qiu, Jiazhang
Format: Article
Language:English
Subjects:
anti-infection
anti-virulence
fisetin
Research Article
Salmonella
T3SS-1 inhibitor
Veterinary Microbiology
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Summary:Salmonella spp. remains a major worldwide health concern that causes significant morbidity and mortality in both humans and animals. The spread of antimicrobial resistant strains has declined the efficacy of conventional chemotherapy. Thus, novel anti-infection drugs or strategies are needed. Anti-virulence strategy represents one of the promising means for the treatment of bacterial infections. In this study, we found that the natural compound fisetin could inhibit Salmonella invasion of host cells by targeting SPI-1 regulation. Fisetin treatment impaired the interaction of the regulatory protein HilD with the promoters of its target genes, thereby suppressing the expression of T3SS-1 effectors as well as structural proteins. Moreover, fisetin treatment could reduce pathology in the Salmonella murine infection model. Collectively, our results suggest that fisetin may serve as a promising lead compound for the development of anti-Salmonella drugs.
ISSN:2165-0497
2165-0497
DOI:10.1128/spectrum.02406-23