Antibacterial activity of Fluopsin C incorporated in different liposomal formulations against multidrug-resistant Staphylococcus aureus.

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The search for new natural products from microbial origin has been standing out afresh as an alternative to obtain bioactive compounds, mainly those with antimicrobial potential. In the medicinal perspective, there is a great demand for new treatments to control diseases caused by multidrug-resistant (MDR) microorganisms, such as Klebsiella pneumoniae carbapenemase-producing (KPC) and methicillin-resistant Staphylococcus aureus (MRSA), among others. The therapeutic alternatives available are scarce, whereas most of them includes last resort medications, due its high toxicity to non-target organs. The Fluopsin C (Flpc), biosynthesized compound by Pseudomonas aeruginosa LV strain’s secondary metabolism, has been showing its promising activity as antimicrobial from natural source, presenting inhibitory activity against a wide scale of microorganisms. However, the considerable cytotoxic effect of FlpC is known, both in vitro and in vivo, besides its low blood availability in in vivo tests. The liposomal encapsulation technique can be applied as a new possibility to overcome those negative factors, as the control of the active compound’s bioavailability becomes possible with no increase in concentration levels and, consequently, no increase in toxicity. Therefore, the aim of this study was the evaluation of FlpC liposomal encapsulation effectiveness as an alternative for future clinical and commercial use. The antimicrobial activity of two different formulations of FlpC liposomal encapsulation were evaluated by broth microdilution and the minimum inhibitory concentration (MIC) was determined. The FlpC was produced from P. aeruginosa LV strain culture in nutrient broth plus copper and purified through different chromatographic methods. The liposomal encapsulation was done via extrusion with one of the formulations containing soy phosphatidylcholine (SPC), cholesterol, polyethylene glycol (PEG) and another one with no PEG addition, both previously characterized and standardized physical-chemically. The microdilution was elaborated in MHB (Mueller-Hinton broth), from the concentrations of 13,3 µg.mL-1 to 0,2 µg.mL-1 against S. aureus PSAM 851 strain, a MDR clinical isolate given by Hospital Universitário Regional do Norte do Paraná (Universidade Estadual de Londrina). Liposomal and free FlpC standards were parallel executed. The obtained results showed a MIC value of 0,41 µg.mL-1 for both formulations and free FlpC. This value indicates the ability of the liposomal encapsulation to maintain the antimicrobial activity of FlpC, what evinces the effectiveness of both FlpC liposomal formulations as a lower cytotoxic alternative to the control of MDR microorganisms. Hereafter, it’s intended to evaluate the FlpC liposomal encapsulation conduct against other microorganism of clinical interest and the execution of in vivo effectiveness tests.

  • 1 Centro de Ciências Exatas / Universidade Estadual de Londrina
  • 2 Departamento de Microbiologia / Centro de Ciências Biológicas / Universidade Estadual de Londrina
  • 3 Centro de Ciências Biológicas / Universidade Estadual de Londrina
  • 4 Centro de Ciências Agrárias / Universidade Estadual de Londrina
  • Inovação e Biotecnologia
natural antimicrobial
Antibacterial resistance