Discovery of synthetic small molecules targeting the central regulator of Salmonella pathogenicity DOI Creative Commons
Abdelhakim Boudrioua, Joe D. Joiner, Iwan Grin

и другие.

Science Advances, Год журнала: 2025, Номер 11(15)

Опубликована: Апрель 11, 2025

The enteric pathogen Salmonella enterica serovar Typhimurium relies on the activity of effector proteins to invade, replicate, and disseminate into host epithelial cells other tissues, thereby causing disease. Secretion injection is mediated by dedicated secretion systems, which hence represent major virulence determinants. Here, we report identification a synthetic small molecule with drug-like properties, C26, suppresses consequently hinders bacterial invasion eukaryotic cells. C26 binds inhibits HilD, transcriptional regulator systems. Although sharing same binding pocket as previously described long-chain fatty acid ligands, HilD unique mode distinct mechanism. We provide evidence intramacrophage present analogs improved potency suitability scaffolds develop antivirulence agents against infections in humans animals.

Язык: Английский

Purpurin suppresses Salmonella invasion of host cells by reducing the secretion of T3SS-1 effector proteins DOI Creative Commons

Zhenxu Shi,

Zhimin Guo, Siqi Li

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 6, 2025

Salmonella Typhimurium (S. Typhimurium, ST) is a food-borne pathogen that can be transmitted from animals to humans and causes symptoms such as diarrhea, fever, vomiting. While antibiotics are commonly used treat clinical infections, the increase in drug resistance has limited their effectiveness. Antivirulence drugs offer new approach treating bacterial infections by targeting specific virulence factors without affecting growth, thus helping combat infection exerting selective pressure on bacteria or inducing resistance. pathogenicity island 1 (SPI-1), encoding type three secretion system (T3SS-1), serves crucial factor for invasion of ST into host cells, making it an ideal target screening anti-Salmonella drugs. This project involved inhibitors through gentamicin protection assay identified purpurin (PPR) capable inhibiting HeLa cells. Subsequent studies revealed PPR had no effect natural growth was not cytotoxic A mechanistic study effectively inhibits T3SS-1 ST. The results animal experiments indicated exhibited significant efficacy mouse enteritis model caused infection, increasing survival rate mice infected with lethal dose 50%, reducing spleen colonization mice, alleviating tissue damage resulting infection. Therefore, represents promising antivirulence targets T3SS may serve hit compound development novel treatment

Язык: Английский

Процитировано

0
Fisetin alleviates Salmonella typhimurium-induced colitis through the TLR2/TLR4-NF-κB pathway, regulating microbiota, and repressing intracellular bacterial proliferation by focal adhesion kinase DOI
Jun Li, Yang Yang, Xinyu Zhang

и другие.

European Journal of Nutrition, Год журнала: 2025, Номер 64(3)

Опубликована: Март 19, 2025

Язык: Английский

Процитировано

0
Discovery of synthetic small molecules targeting the central regulator of Salmonella pathogenicity DOI Creative Commons
Abdelhakim Boudrioua, Joe D. Joiner, Iwan Grin

и другие.

Science Advances, Год журнала: 2025, Номер 11(15)

Опубликована: Апрель 11, 2025

The enteric pathogen Salmonella enterica serovar Typhimurium relies on the activity of effector proteins to invade, replicate, and disseminate into host epithelial cells other tissues, thereby causing disease. Secretion injection is mediated by dedicated secretion systems, which hence represent major virulence determinants. Here, we report identification a synthetic small molecule with drug-like properties, C26, suppresses consequently hinders bacterial invasion eukaryotic cells. C26 binds inhibits HilD, transcriptional regulator systems. Although sharing same binding pocket as previously described long-chain fatty acid ligands, HilD unique mode distinct mechanism. We provide evidence intramacrophage present analogs improved potency suitability scaffolds develop antivirulence agents against infections in humans animals.

Язык: Английский

Процитировано

0