Baicalin protects mice from Staphylococcus aureus pneumonia via inhibition of the cytolytic activity of α-hemolysin

The Journal of Infectious Diseases
Jiazhang QiuXuming Deng

Abstract

α-Hemolysin (Hla) is a self-assembling, channel-forming toxin that is secreted by Staphylococcus aureus and is central to the pathogenesis of pulmonary, intraperitoneal, intramammary, and corneal infections in animal models. In this study, we report that baicalin (BAI), a natural compound that lacks anti-S. aureus activity, could inhibit the hemolytic activity of Hla. Using molecular dynamics simulations and mutagenesis assays, we further demonstrate that BAI binds to the binding sites of Y148, P151, and F153 in the Hla. This binding interaction inhibits heptamer formation. Furthermore, when added to S. aureus cultures, BAI prevents Hla-mediated human alveolar epithelial (A549) cell injury. In vivo studies further demonstrated that BAI protects mice from S. aureus pneumonia. These findings indicate that BAI hinders the cell lysis activity of Hla through a novel mechanism of interrupting the formation of heptamer, which may lead to the development of novel therapeutics that aim against S. aureus Hla.

References

Jan 1, 1986·Molecular & General Genetics : MGG·P RecseiR P Novick
Jun 1, 1994·Infection and Immunity·M C CalleganR J O'Callaghan
Aug 26, 1998·The New England Journal of Medicine·F D Lowy
Jan 11, 2000·Clinical Microbiology Reviews·M M DingesP M Schlievert
Nov 29, 2005·The Lancet Infectious Diseases·Heiman F L WertheimJan L Nouwen
Mar 22, 2006·Evidence-based Complementary and Alternative Medicine : ECAM·Lynn S AdamsDavid Heber
Nov 15, 2006·Infection and Immunity·Juliane Bubeck WardenburgOlaf Schneewind
Jun 19, 2007·Bioorganic & Medicinal Chemistry·Vladimir A KarginovSidney M Hecht
Dec 15, 2007·Nature Reviews. Microbiology·Lynette CegelskiScott J Hultgren
Feb 13, 2008·The Journal of Experimental Medicine·Juliane Bubeck Wardenburg, Olaf Schneewind
Jul 22, 2008·Current Opinion in Chemical Biology·Sonia Escaich
Apr 22, 2009·Infection and Immunity·Brook E Ragle, Juliane Bubeck Wardenburg
Oct 7, 2009·Expert Review of Anti-infective Therapy·Ronald PangilinanGlenn Tillotson
Oct 7, 2009·Antimicrobial Agents and Chemotherapy·Brook E RagleJuliane Bubeck Wardenburg
Jan 19, 2010·Nature Reviews. Drug Discovery·David A Rasko, Vanessa Sperandio
Mar 23, 2011·The Journal of Antimicrobial Chemotherapy·Pavel NovyLadislav Kokoska

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Citations

Feb 5, 2013·European Journal of Medicinal Chemistry·Xiaodi NiuXuming Deng
Mar 8, 2013·Journal of Asian Natural Products Research·Xiao-Han DaiMing-Jun Zhang
Sep 1, 2014·Microbial Pathogenesis·Qianchao WuHaihua Feng
Jan 1, 2014·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Feng TangBing Li
Dec 25, 2015·Molecular Pharmacology·Xiaoran ZhaoXiaodi Niu
Jan 31, 2016·Biochemical Pharmacology·Hongen LiXuming Deng
Sep 10, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Bin LiCheng Guo
Jul 21, 2016·Chemical Reviews·Laura Nunes SilvaDanielle Silva Trentin
Nov 24, 2016·World Journal of Microbiology & Biotechnology·Shui LiuJianfeng Wang
Jan 11, 2016·Chemistry : a European Journal·Jan VomackaStephan A Sieber
Apr 25, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Guizhen WangHongsu Wang
Oct 20, 2018·Journal of Cellular and Molecular Medicine·Jianfeng WangXuming Deng
Nov 3, 2016·American Journal of Physiology. Cell Physiology·Pin LvMei Han
Jun 4, 2019·Frontiers in Cellular and Infection Microbiology·Lanxiang JiangJianfeng Wang
May 28, 2019·FEMS Microbiology Letters·Shui LiuXuming Deng
Sep 25, 2019·Toxins·Neža OmersaGregor Anderluh
Apr 8, 2015·The Journal of Biological Chemistry·Jing DongXuming Deng
Jul 16, 2017·Applied Microbiology and Biotechnology·Zihao TengJianfeng Wang
Aug 15, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Ouyang PingYin Lizi
Dec 18, 2018·Frontiers in Cellular and Infection Microbiology·Guizhen WangJianfeng Wang
Jul 4, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Yan XuLiping Sun

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