Kart Didem, Reçber Tuba, Nemutlu Emirhan, Sagiroglu Meral
Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey.
Department of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey.
Antibiotics (Basel). 2021 Apr 9;10(4):414. doi: 10.3390/antibiotics10040414.
Alternative anti-biofilm agents are needed to combat infections. The mechanisms behind these new agents also need to be revealed at a molecular level.
The anti-biofilm effects of 10 plant-derived compounds on biofilms were investigated using minimum biofilm eradication concentration (MBEC) and virulence assays. The effects of ciprofloxacin and compound combinations on in mono and triple biofilms were compared. A metabolomic approach and qRT-PCR were applied to the biofilms treated with ciprofloxacin in combination with baicalein, esculin hydrate, curcumin, and cinnamaldehyde at sub-minimal biofilm inhibitory concentration (MBIC) concentrations to highlight the specific metabolic shifts between the biofilms and to determine the quorum sensing gene expressions, respectively.
The combinations of ciprofloxacin with curcumin, baicalein, esculetin, and cinnamaldehyde showed more reduced MBICs than ciprofloxacin alone. The quorum sensing genes were downregulated in the presence of curcumin and cinnamaldehyde, while upregulated in the presence of baicalein and esculin hydrate rather than for ciprofloxacin alone. The combinations exhibited different killing effects on in mono and triple biofilms without affecting its virulence. The findings of the decreased metabolite levels related to pyrimidine and lipopolysaccharide synthesis and to down-regulated alginate and expressions strongly indicate the role of multifactorial mechanisms for curcumin-mediated growth inhibition.
The use of curcumin, baicalein, esculetin, and cinnamaldehyde with ciprofloxacin will help fight against biofilms. To the best of our knowledge, this is the first study of its kind to define the effect of plant-based compounds as possible anti-biofilm agents with low MBICs for the treatment of biofilms through metabolomic pathways.
需要新型抗生物膜药物来对抗感染。这些新型药物背后的作用机制也需要在分子水平上揭示。
使用最低生物膜清除浓度（MBEC）和毒力测定法研究了10种植物源化合物对生物膜的抗生物膜作用。比较了环丙沙星和化合物组合对单一生物膜和三重生物膜的影响。采用代谢组学方法和qRT-PCR对在亚最低生物膜抑制浓度（MBIC）下用环丙沙星与黄芩素、七叶苷、姜黄素和肉桂醛联合处理的生物膜进行研究，以突出生物膜之间的特定代谢变化，并分别确定群体感应基因的表达。
环丙沙星与姜黄素、黄芩素、七叶亭和肉桂醛的组合显示出比单独使用环丙沙星更低的MBIC。群体感应基因在姜黄素和肉桂醛存在时下调，而在黄芩素和七叶苷存在时上调，而不是单独使用环丙沙星时。这些组合对单一生物膜和三重生物膜表现出不同的杀伤作用，且不影响其毒力。与嘧啶和脂多糖合成相关的代谢物水平降低以及藻酸盐和基因表达下调的结果强烈表明了姜黄素介导的生长抑制的多因素机制作用。
将姜黄素、黄芩素、七叶亭和肉桂醛与环丙沙星联合使用将有助于对抗生物膜。据我们所知，这是同类研究中首次通过代谢组学途径将植物基化合物定义为可能具有低MBIC的抗生物膜药物用于治疗生物膜的研究。
