Department of Chemical Engineering, Howard University, Washington, District of Columbia, United States of America.
Department of Chemistry and Biochemistry, California State University, Dominguez Hills, Carson, California, United States of America.
PLoS One. 2019 Apr 18;14(4):e0215273. doi: 10.1371/journal.pone.0215273. eCollection 2019.
Phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) is a highly conserved, multistep chemical process which uses phosphate transfer to regulate the intake and use of sugars and other carbohydrates by bacteria. In addition to controlling sugar uptake, the PTS regulates several bacterial cellular functions such as chemotaxis, glycogen metabolism, catabolite repression and biofilm formation. Previous studies have shown that the phosphoenolpyruvate (PEP) to pyruvate ratio is a critical determinant of PTS functions. This study shows that 2-oxo-4-phenyl-2,5-dihydro-3-furancarbonitrile (MW01), a compound with structural similarity to known natural products, induces Vibrio cholerae to grow preferentially in the biofilm mode in a mechanism that involves interaction with pyruvate. Spectrophotometric assays were used to monitor bacterial growth kinetics in microtiter plates and quantitatively evaluate biofilm formation in borosilicate glass tubes. Evidence of MW01 and pyruvate interactions was determined by nuclear magnetic resonance spectroscopy. Given the established connection between PTS activity and biofilm formation, this study also highlights the potential impact that small-molecule modulators of the PTS may have in the development of innovative approaches to manage desired and undesired microbial cultures in clinical, industrial and environmental settings.
磷酸烯醇式丙酮酸-碳水化合物磷酸转移酶系统（PTS）是一个高度保守的多步骤化学过程，利用磷酸转移来调节细菌对糖和其他碳水化合物的摄取和利用。除了控制糖的摄取外，PTS 还调节细菌的几种细胞功能，如趋化性、糖原代谢、分解代谢物阻遏和生物膜形成。先前的研究表明，磷酸烯醇丙酮酸（PEP）与丙酮酸的比值是 PTS 功能的关键决定因素。本研究表明，2-氧代-4-苯基-2,5-二氢-3-呋喃甲腈（MW01），一种与已知天然产物结构相似的化合物，通过与丙酮酸相互作用，诱导霍乱弧菌优先以生物膜模式生长。分光光度法测定用于监测微孔板中的细菌生长动力学，并定量评估硼硅酸盐玻璃管中的生物膜形成。通过核磁共振波谱确定了 MW01 和丙酮酸相互作用的证据。鉴于 PTS 活性与生物膜形成之间的既定联系，本研究还强调了小分子 PTS 调节剂在开发创新方法以管理临床、工业和环境环境中所需和不需要的微生物培养物方面的潜在影响。
