Harrison Zoe L, Awais Rukhsana, Harris Michael, Raji Babatunde, Hoffman Brian C, Baker Daniel L, Jennings Jessica Amber
Department of Biomedical Engineering, University of Memphis, Memphis, TN, United States.
Department of Chemistry, University of Memphis, Memphis, TN, United States.
Front Microbiol. 2021 Jun 9;12:645180. doi: 10.3389/fmicb.2021.645180. eCollection 2021.
Fatty-acid signaling molecules can inhibit biofilm formation, signal dispersal events, and revert dormant cells within biofilms to a metabolically active state. We synthesized 2-heptylcyclopropane-1-carboxylic acid (2CP), an analog of -2-decenoic acid (C2DA), which contains a cyclopropanated bond that may lock the signaling factor in an active state and prevent isomerization to its least active -configuration (T2DA). 2CP was compared to C2DA and T2DA for ability to disperse biofilms formed by and . 2CP at 125 μg/ml dispersed approximately 100% of cells compared to 25% for C2DA; both 2CP and C2DA had significantly less biofilm remaining compared to T2DA, which achieved no significant dispersal. 2CP at 125 μg/ml dispersed approximately 60% of biofilms, whereas C2DA and T2DA at the same concentration dispersed 40%. When combined with antibiotics tobramycin, tetracycline, or levofloxacin, 2CP decreased the minimum concentration required for biofilm inhibition and eradication, demonstrating synergistic and additive responses for certain combinations. Furthermore, 2CP supported fibroblast viability above 80% for concentrations below 1 mg/ml. This study demonstrates that 2CP shows similar or improved efficacy in biofilm dispersion, inhibition, and eradication compared to C2DA and T2DA and thus may be promising for use in preventing infection for healthcare applications.
脂肪酸信号分子可以抑制生物膜形成、信号传播事件,并使生物膜内的休眠细胞恢复到代谢活跃状态。我们合成了2-庚基环丙烷-1-羧酸(2CP),它是-2-癸烯酸(C2DA)的类似物,含有一个环丙烷化键,该键可能将信号因子锁定在活性状态,并防止其异构化为活性最低的-构型(T2DA)。将2CP与C2DA和T2DA在分散由 和 形成的生物膜的能力方面进行了比较。125μg/ml的2CP能分散约100%的 细胞,而C2DA为25%;与未实现显著分散的T2DA相比,2CP和C2DA残留的生物膜都显著更少。125μg/ml的2CP能分散约60%的 生物膜,而相同浓度的C2DA和T2DA能分散40%。当与抗生素妥布霉素、四环素或左氧氟沙星联合使用时,2CP降低了生物膜抑制和根除所需的最低浓度,表明某些组合具有协同和相加反应。此外,对于浓度低于1mg/ml的2CP,其对成纤维细胞活力的支持率高于80%。这项研究表明,与C2DA和T2DA相比,2CP在生物膜分散、抑制和根除方面显示出相似或更高的功效,因此在医疗保健应用中预防感染方面可能具有应用前景。