title: A phytoanticipin derivative, sodium houttuyfonate, induces in vitro synergistic effects with levofloxacin against biofilm formation by Pseudomonas aeruginosa.
abstract: Antibiotic resistance has become the main deadly factor in infections, as bacteria can protect themselves by hiding in a self-constructed biofilm. Consequently, more attention is being paid to the search for "non-antibiotic drugs" to solve this problem. Phytoanticipins, the natural antibiotics from plants, could be a suitable alternative, but few works on this aspect have been reported. In this study, a preliminary study on the synergy between sodium houttuyfonate (SH) and levofloxacin (LFX) against the biofilm formation of Pseudomonas aeruginosa was performed. The minimal inhibitory concentrations (MIC) of LFX and SH, anti-biofilm formation and synergistic effect on Pseudomonas aeruginosa, and quantification of alginate were determined by the microdilution method, crystal violet (CV) assay, checkerboard method, and hydroxybiphenyl colorimetry. The biofilm morphology of Pseudomonas aeruginosa was observed by fluorescence microscope and scanning electric microscope (SEM). The results showed that: (i) LFX and SH had an obvious synergistic effect against Pseudomonas aeruginosa with MIC values of 0.25 μg/mL and 128 μg/mL, respectively; (ii) ½ × MIC SH combined with 2 × MIC LFX could suppress the biofilm formation of Pseudomonas aeruginosa effectively, with up to 73% inhibition; (iii) the concentration of alginate decreased dramatically by a maximum of 92% after treatment with the combination of antibiotics; and (iv) more dead cells by fluorescence microscope and more removal of extracellular polymeric structure (EPS) by SEM were observed after the combined treatment of LFX and SH. Our experiments demonstrate the promising future of this potent antimicrobial agent against biofilm-associated infections.
authors.affiliation: Laboratory of Microbiology and Immunology, School of Chinese and Western Integrative Medicine, Anhui University of Traditional Chinese Medicine, Hefei 230038, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.forename: Huijuan
authors.initials: H
authors.lastname: Cheng
authors.forename: Changzhong
authors.initials: C
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000473:Alkanes / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D004338:Drug Combinations; D004357:Drug Synergism; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D013447:Sulfites / Q000494:pharmacology*
chemical_list: D000473:Alkanes; D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D013447:Sulfites; C473296:sodium houttuyfonate; D064704:Levofloxacin; D015242:Ofloxacin