Inhibition of biofilm formation in Bacillus subtilis by new halogenated furanones

Abstract

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.

Targeting microbial biofilms using Ficin, a nonspecific plant protease

“…We investigated whether Ficin is able to disrupt bacterial biofilms formed by S. aureus and S. epidermidis , the bacteria colonizing wounds and thus retarding wound healing30. To do so, the bacteria were grown in BM broth earlier developed3132 for 72 h on 24-well TC-treated plates that provided a representative and repeatable formation of the rigid biofilm strongly attached to the surfaces, in contrast to Müller-Hinton broth, Trypticase soy broth or LB-medium (Fig. 1).…”

“…The Müller-Hinton broth (Fluka) or Trypticase soy broth (Sigma) did not provide stable biofilm formation by both Staphylococcus aureus and Staphylococcus epidermidis , as is has been determined in preliminary studies (Fig. 1), thus the modified Basal medium (BM) (glucose 5 g, peptone 7 g, MgSO 4  × 7H 2 O 2.0 g and CaCl 2  × 2H 2 O 0.05 g in 1.0 liter tap water) was used for the biofilm formation assays3139. Bacteria were grown for 48–72 hours as indicated under static conditions at 37 °C to obtain rigid biofilm structures.…”

Design, synthesis, andIn vitroantituberculosis activity of 2(5H)-Furanone derivatives

“…The product was purified by flash column chromatography. The furanone carbonyl does not appear on the 13 C NMR spectrum, this can be rationalized due to the slow relaxation basis.…”

“…Column chromatography was performed using Merck Kielselgel 60 (particle size 0.040-0.063 mm), while thin layer chromatography was done on Merck aluminum-supported silica gel 60 F 254 . NMR spectra were recorded at 400 MHz for 1 H NMR and 100 MHz for 13 C NMR on a Varian Unity INOVA 400 NMR as a solution in either CDCl 3 or DMSO-d 6 . Chemical shift data (d-values) are recorded in parts per million (ppm) relative to tetramethylsilane as an internal standard, coupling constants are quoted in hertz (see Supporting Information file for representative NMR spectra).…”

“…In particular, compounds bearing the 2-furanone backbone have exhibited diverse biological activities, such as antiprotozoal, antibacterial (including inhibition of biofilm formation), antimycobacterial, antitumoral, antifungal, and cyclooxygenase-2 inhibition (8)(9)(10)(11)(12)(13)(14). The efficacy of several butyrolactone derivatives against mycobacteria suggests that these structures be a new template for tuberculosis drug development (14,15).…”