Department of Pharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, United States.
Department of Biological Sciences, Columbia University, 617 Fairchild Center, New York, New York 10027, United States.
ACS Infect Dis. 2020 Apr 10;6(4):603-612. doi: 10.1021/acsinfecdis.9b00424. Epub 2020 Jan 3.
Biofilm inhibition by exogenous molecules has been an attractive strategy for the development of novel therapeutics. We investigated the biofilm inhibitor taurolithocholic acid (TLCA) and its effects on the specialized metabolism, virulence, and biofilm formation of the clinically relevant bacterium strain PA14. Our study shows that TLCA alters the specialized metabolism, thereby affecting colony biofilm physiology. We observed an upregulation of metabolites correlated to virulence such as the siderophore pyochelin. A wax moth virulence assay confirmed that treatment with TLCA increases the virulence of . On the basis of our results, we believe that future endeavors to identify biofilm inhibitors must consider how a putative lead alters the specialized metabolism of a bacterial community to prevent pathogens from entering a highly virulent state.
外源性分子抑制生物膜的形成一直是开发新型治疗方法的一种有吸引力的策略。我们研究了生物膜抑制剂牛磺胆酸(TLCA)及其对临床相关细菌 株 PA14 的特殊代谢、毒力和生物膜形成的影响。我们的研究表明,TLCA 改变了特殊代谢,从而影响了 菌落生物膜生理学。我们观察到与毒力相关的代谢物上调,如铁载体焦脱镁叶绿酸。一个黄粉甲幼虫的毒力测定证实,TLCA 的处理增加了 的毒力。基于我们的结果,我们认为,未来识别生物膜抑制剂的努力必须考虑到假定的先导化合物如何改变细菌群落的特殊代谢,以防止病原体进入高度毒力状态。