Frontiers in cellular and infection microbiology · 2026
A novel SaeS-targeting antivirulence antagonist screened against methicillin-resistant Staphylococcus aureus.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yao Jiahao, Ai Duiyuan, Duan Huanhuan
Аннотация
BACKGROUND: The SaeRS two-component system is a major virulence regulator in Staphylococcus aureus, and its sensor kinase SaeS represents a potential target for small-molecule intervention.
METHODS: In this study, we constructed a library of 1,093 compounds from PubChem and carried out structure-guided virtual screening against the SaeS kinase domain. This approach identified an amide-based candidate, designated Saeamid-1. Molecular docking and molecular dynamics simulations supported stable binding of Saeamid-1 within the nucleotide-binding region of SaeS, with a docking score of -9.884 kcal/mol.
RESULTS: The compound had only limited effects on bacterial growth. In contrast, it reduced hemolytic activity and biofilm biomass in USA300 by 65.74% and 88.77%, respectively. RT-qPCR analysis showed that Saeamid-1 reduced the expression of saeR, saeS, and the SaeRS-associated virulence gene spa.
CONCLUSIONS: Taken together, these findings identify Saeamid-1 as a promising antivirulence candidate that targets SaeS in methicillin-resistant Staphylococcus aureus and provide a basis for further development of therapeutic strategies directed against the SaeRS pathway.
METHODS: In this study, we constructed a library of 1,093 compounds from PubChem and carried out structure-guided virtual screening against the SaeS kinase domain. This approach identified an amide-based candidate, designated Saeamid-1. Molecular docking and molecular dynamics simulations supported stable binding of Saeamid-1 within the nucleotide-binding region of SaeS, with a docking score of -9.884 kcal/mol.
RESULTS: The compound had only limited effects on bacterial growth. In contrast, it reduced hemolytic activity and biofilm biomass in USA300 by 65.74% and 88.77%, respectively. RT-qPCR analysis showed that Saeamid-1 reduced the expression of saeR, saeS, and the SaeRS-associated virulence gene spa.
CONCLUSIONS: Taken together, these findings identify Saeamid-1 as a promising antivirulence candidate that targets SaeS in methicillin-resistant Staphylococcus aureus and provide a basis for further development of therapeutic strategies directed against the SaeRS pathway.