Matrine Restores Colistin Efficacy Against mcr-1-Carrying Escherichia coli DOI Creative Commons

Zhinan Wang,

Xiaowei Li, Liang Zhao

и другие.

Molecules, Год журнала: 2025, Номер 30(10), С. 2122 - 2122

Опубликована: Май 11, 2025

The emergence of mcr-1-mediated colistin resistance has become a critical global health concern, highlighting the urgent need for innovative approaches to restore colistin’s therapeutic potential. In this study, we evaluated antibacterial activity four matrine-type alkaloids—namely, matrine, oxymatrine, sophocarpine, and sophoramine—against mcr-1-positive Escherichia coli. While these alkaloids showed limited efficacy when used alone, combination matrine with exhibited remarkable synergistic effects, as demonstrated by checkerboard assays time-kill curve analyses. matrine–colistin caused minimal erythrocyte damage while effectively attenuating development in vitro. This synergy was further corroborated murine infection model, where significantly reduced bacterial loads target tissues. Mechanistic studies revealed that enhances antimicrobial disrupting membrane integrity, increasing intracellular accumulation, triggering reactive oxygen species-mediated oxidative damage. Collectively, findings highlight potential promising adjuvant overcome resistance, providing novel approach address challenge infections cause multidrug-resistant Gram-negative bacteria.

Язык: Английский

Matrine Restores Colistin Efficacy Against mcr-1-Carrying Escherichia coli DOI Creative Commons

Zhinan Wang,

Xiaowei Li, Liang Zhao

и другие.

Molecules, Год журнала: 2025, Номер 30(10), С. 2122 - 2122

Опубликована: Май 11, 2025

The emergence of mcr-1-mediated colistin resistance has become a critical global health concern, highlighting the urgent need for innovative approaches to restore colistin’s therapeutic potential. In this study, we evaluated antibacterial activity four matrine-type alkaloids—namely, matrine, oxymatrine, sophocarpine, and sophoramine—against mcr-1-positive Escherichia coli. While these alkaloids showed limited efficacy when used alone, combination matrine with exhibited remarkable synergistic effects, as demonstrated by checkerboard assays time-kill curve analyses. matrine–colistin caused minimal erythrocyte damage while effectively attenuating development in vitro. This synergy was further corroborated murine infection model, where significantly reduced bacterial loads target tissues. Mechanistic studies revealed that enhances antimicrobial disrupting membrane integrity, increasing intracellular accumulation, triggering reactive oxygen species-mediated oxidative damage. Collectively, findings highlight potential promising adjuvant overcome resistance, providing novel approach address challenge infections cause multidrug-resistant Gram-negative bacteria.

Язык: Английский

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