Inhibitory effect of 1,2,4-triazole-ciprofloxacin hybrids on Haemophilus parainfluenzae and Haemophilus influenzae biofilm formation in vitro under stationary conditions.
Haemophilus parainfluenzae and Haemophilus influenzae, upper respiratory tract microbiota representatives, are able to colonize natural and artificial surfaces as biofilm. The aim of the present study was to assay the effect of ten 1,2,4-triazole-ciprofloxacin hybrids on planktonic or biofilm-forming haemophili cells in vitro under stationary conditions on the basis of MICs (minimal inhibitory concentrations) and MBICs (minimal biofilm inhibitory concentrations). In addition, anti-adhesive properties of these compounds were examined. The reference strains of H. parainfluenzae and H. influenzae were included. The broth microdilution microtiter plate (MTP) method with twofold dilution of the compounds, or ciprofloxacin (reference agent) in 96-well polystyrene microplates, was used. The optical density (OD) reading was made spectrophotometrically at a wavelength of 570 nm (OD570) both to measure bacterial growth and to detect biofilm-forming cells under the same conditions with 0.1% crystal violet. The following values of parameters were estimated for 1,2,4-triazole-ciprofloxacin hybrids - MIC = 0.03-15.63 mg/L, MBIC = 0.03-15.63 mg/L, MBIC/MIC = 0.125-8, depending on the compound, and for ciprofloxacin - MIC = 0.03-0.06 mg/L, MBIC = 0.03-0.12 mg/L, MBIC/MIC = 1-2. The observed strong anti-adhesive properties (95-100% inhibition) of the tested compounds were reversible during long-term incubation at subinhibitory concentrations. Thus, 1,2,4-triazole-ciprofloxacin hybrids may be considered as starting compounds for designing improved agents not only against planktonic but also against biofilm-forming Haemophilus spp. cells.
Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodźki Str. 1, 20-093 Lublin, Poland. Electronic address: urszula.kosikowska@umlub.pl.
Urszula
U
Kosikowska
Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodźki Str. 1, 20-093 Lublin, Poland. Electronic address: sylwia.andrzejczuk@umlub.pl.
Sylwia
S
Andrzejczuk
Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland. Electronic address: tomasz.plech@umlub.pl.
Tomasz
T
Plech
Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodźki Str. 1, 20-093 Lublin, Poland. Electronic address: anna.malm@umlub.pl.
Anna
A
Malm
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002939:Ciprofloxacin / Q000494:pharmacology*; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000502:physiology; D044135:Haemophilus parainfluenzae / Q000187:drug effects* / Q000502:physiology; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D013053:Spectrophotometry; D014230:Triazoles / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D014230:Triazoles; C045575:1,2,4-triazole; D002939:Ciprofloxacin
1,2,4-Triazole-ciprofloxacin hybrid; Anti-biofilm and anti-adhesive activity; Haemophilus spp.