Sharafutdinov Irshad S, Pavlova Anna S, Khabibrakhmanova Alsu M, Faizova Roza G, Kurbangalieva Almira R, Tanaka Katsunori, Trizna Elena Y, Baidamshina Diana R, Bogachev Mikhail I, Kayumov Airat R
Laboratory of Molecular Genetics of Microorganisms, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya street, Kazan 420008, Russia.
Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya street, Kazan 420008, Russia.
New Microbiol. 2019 Jan;42(1):29-36. Epub 2019 Jan 23.
Among a variety of antimicrobial compounds, the derivatives of 2(5H)-furanone exhibit different effects on Firmicutes and Proteobacteria. While inhibiting quorum-dependent biofilm formation and virulence factor expression by Gram-negative bacteria through specific interference with the AI-2 signaling pathways, these compounds demonstrate bactericidal effects against Gram-positive bacteria. Here we report that 3,4-dichloro-5(S)-[(1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yloxy]-2(5H)-furanone designed as F123 inhibits growth and biofilm formation by the food-poisoning bacterium Bacillus cereus at 8 μg/ ml and kills bacteria at 16 μg/ml. While the growth of Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus, Bacillus subtilis were also inhibited at 8-16 μg/ml of F123, no bactericidal effect on these strains was observed at concentrations up to 128 μg/ml, suggesting pronounced specificity of F123 for B. cereus. In a checker-board assay F123 increased the efficacy of amikacin, gentamicin and benzalkonium chloride against B. cereus with medians of fractional inhibitory concentration index of 0.38, 0.56 and 0.56, respectively. Moreover, the number of viable B. cereus cells in biofilm was reduced by more than 3 orders of magnitude at 64 μg/ml of F123, suggesting its chemotype as a promising enhancer for specific treatment of B. cereus-associated topical infections, including biofilm-embedded bacteria.
在多种抗菌化合物中，2(5H)-呋喃酮的衍生物对厚壁菌门和变形菌门表现出不同的作用。这些化合物通过特异性干扰AI-2信号通路抑制革兰氏阴性菌群体感应依赖性生物膜形成和毒力因子表达，同时对革兰氏阳性菌具有杀菌作用。在此我们报告，设计为F123的3,4-二氯-5(S)-[(1S,2R,4S)-1,7,7-三甲基双环[2.2.1]庚-2-基氧基]-2(5H)-呋喃酮在8 μg/ml时可抑制食物中毒病原菌蜡样芽孢杆菌的生长和生物膜形成，并在16 μg/ml时杀死细菌。虽然在8-16 μg/ml的F123作用下，金黄色葡萄球菌、表皮葡萄球菌、藤黄微球菌、枯草芽孢杆菌的生长也受到抑制，但在浓度高达128 μg/ml时未观察到对这些菌株的杀菌作用，这表明F123对蜡样芽孢杆菌具有明显的特异性。在棋盘法试验中，F12能提高阿米卡星、庆大霉素和苯扎氯铵对蜡样芽孢杆菌的疗效，其分数抑制浓度指数中位数分别为0.38、0.56和0.56。此外，在64 μg/ml的F123作用下，生物膜中蜡样芽孢杆菌的活菌数减少了3个以上数量级，这表明其化学类型有望成为治疗蜡样芽孢杆菌相关局部感染（包括生物膜包埋细菌）的有效增强剂。
