Gram-positive bacteria can cause various infections including hospital-acquired infections. While in the biofilm, the resistance of bacteria to both antibiotics and the human immune system is increased causing difficulties in the treatment. Bacillus subtilis, a non-pathogenic Gram-positive bacterium, is widely used as a model organism for studying biofilm formation. Here we investigated the effect of novel synthesized chloro- and bromo-containing 2(5H)-furanones on biofilm formation by B. subtilis. Mucobromic acid (3,4-dibromo-5-hydroxy-2(5H)-furanone) and the two derivatives of mucochloric acid (3,4-dichloro-5-hydroxy-2(5H)-furanone)-F8 and F12-were found to inhibit the growth and to efficiently prevent biofilm formation by B. subtilis. Along with the low production of polysaccharide matrix and repression of the eps operon, strong repression of biofilm-related yqxM also occurred in the presence of furanones. Therefore, our data confirm that furanones affect significantly the regulatory pathway(s) leading to biofilm formation. We propose that the global regulator, Spo0A, is one of the potential putative cellular targets for these compounds.
Gram-positive bacteria cause a wide spectrum of infectious diseases, including nosocomial infections. While in the biofilm, bacteria exhibit increased resistance to antibiotics and the human immune system, causing difficulties in treatment. Thus, the development of biofilm formation inhibitors is a great challenge in pharmacology. The gram-positive bacterium Bacillus subtilis is widely used as a model organism for studying biofilm formation. Here, we report on the effect of new synthesized 2(5H)-furanones on the biofilm formation by B.subtilis cells. Among 57 compounds tested, sulfur-containing derivatives of 2(5H)-furanone (F12, F15, and F94) repressed biofilm formation at a concentration of 10 μg/ml. Derivatives F12 and F94 were found to inhibit the biosynthesis of GFP from the promoter of the eps operon encoding genes of the biofilm exopolysaccharide synthesis (EPS). Using the differential fluorescence staining of alive/dead cells, we demonstrated an increased bacterial sensitivity to antibiotics (kanamycin and chloramphenicol) in the presence of F12, F15, and F94, with F12 being the most efficient one. The derivative F15 was capable of disrupting an already formed biofilm and thereby increasing the efficiency of antibiotics.
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