Abstract
Platostoma rotundifolium (Briq.) A. J. Paton aerial parts are widely used in Burundi traditional medicine to treat infectious diseases. In order to investigate their probable antibacterial activities, crude extracts from P. rotundifolium were assessed for their bactericidal and anti-virulence properties against an opportunistic bacterial model, Pseudomonas aeruginosa PAO1. Whereas none of the tested extracts exert bacteriostatic and/or bactericidal proprieties, the ethyl acetate and dichloromethane extracts exhibit anti-virulence properties against Pseudomonas aeruginosa PAO1 characterized by an alteration in quorum sensing gene expression and biofilm formation without affecting bacterial viability. Bioguided fractionation of the ethyl acetate extract led to the isolation of major anti-virulence compounds that were identified from nuclear magnetic resonance and high-resolution molecular spectroscopy spectra as cassipourol, β-sitosterol and α-amyrin. Globally, cassipourol and β-sitosterol inhibit quorum sensing-regulated and -regulatory genes expression in las and rhl systems without affecting the global regulators gacA and vfr, whereas α-amyrin had no effect on the expression of these genes. These terpenoids disrupt the formation of biofilms at concentrations down to 12.5, 50 and 50 µM for cassipourol, β-sitosterol and α-amyrin, respectively. Moreover, these terpenoids reduce the production of total exopolysaccharides and promote flagella-dependent motilities (swimming and swarming). The isolated terpenoids exert a wide range of inhibition processes, suggesting a complex mechanism of action targeting P. aeruginosa virulence mechanisms which support the wide anti-infectious use of this plant species in traditional Burundian medicine.
Highlights
Assuming that the success of bacterial infection relies on an optimal expression of virulence [1], an attractive anti-pathogenic approach consists in targeting these mechanisms [2,3,4]
We report on antibacterial activities of P. rotundifolium extracts towards P. aeruginosa PAO1, an opportunistic pathogen which infects immunocompromised patients and describe the isolation, the identification and the characterization of antibacterial properties of major isolated bioactive compounds
The MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) of five P. rotundifolium aerial part extracts with different degrees of polarity were higher than 4000 μg/mL on P. aeruginosa PAO1, indicating an extremely weak potential as a direct antibiotic; by comparison, the MIC and MBC for tobramycin, an antibiotic generally used to treat patients with cystic fibrosis infected by P. aeruginosa [17], were 1 and 2 μg/mL, respectively
Summary
Assuming that the success of bacterial infection relies on an optimal expression of virulence [1], an attractive anti-pathogenic approach consists in targeting these mechanisms [2,3,4]. The persistence of bacterial infection is linked to their ability to form structured biofilms which represent a protective barrier against antibiotics and immune defense, allowing survival and further re-dissemination [6,7] These faculties are intimately interconnected to quorum sensing (QS), a bacterial cell-to-cell communication that allows bacteria to coordinate their behavior depending on their population density, through the release and perception of small diffusible molecules called “auto-inducers” [8] which induce the production of several virulence factors and modulate bacterial behaviors, including biofilm lifestyle growth [9]. Many bioactive molecules have been reported to exert modulatory properties on bacterial virulence expression and most of them are naturally-derived compounds, such as halogenated C-30 and C-56 furanones, inspired from natural compounds produced by the marine macroalga Delisea pulchra, which reduce biofilm and target the QS systems in P. aeruginosa, an important human, animal and plant pathogen [13]. We report on antibacterial activities of P. rotundifolium extracts towards P. aeruginosa PAO1, an opportunistic pathogen which infects immunocompromised patients and describe the isolation, the identification and the characterization of antibacterial properties of major isolated bioactive compounds
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