Antibiofilm activity of aminopropanol derivatives against Pseudomonas aeruginosa

  • D. M. Dudikova SI «Institute of pharmacology and toxicology of NAMS of Ukraine», Kyiv
  • Z. S. Suvorova SI «Institute of pharmacology and toxicology of NAMS of Ukraine», Kyiv
  • V. V. Nedashkivska SI «Institute of pharmacology and toxicology of NAMS of Ukraine», Kyiv
  • A. O. Sharova SI «Institute of pharmacology and toxicology of NAMS of Ukraine», Kyiv
  • M. L. Dronova SI «Institute of pharmacology and toxicology of NAMS of Ukraine», Kyiv
  • N. O. Vrynchanu SI «Institute of pharmacology and toxicology of NAMS of Ukraine», Kyiv
Keywords: microbial cells communities, microorganisms, Pseudomonas aeruginosa, aminopropanol derivatives, antibacterial agents

Abstract

Bacterial biofilm, particularly formed by Pseudomonas aeruginosa, are a cause of severe chronic infectious diseases. Bacteria within a biofilm are phenotypically more resistant to antibiotics and the macroorganism immune system, making it an important virulence factor for many microbes.

The aminopropanol derivatives with adamantyl (KVM-97) and N-alkylaryl radicals (KVM-194, KVM-204, KVM-261, and KVM-262) were used as study object. The aim of this study was to investigate the antibiofilm activity of compounds on biofilm formation and on mature biofilm of P. aeruginosa. The effects of the aminopropanol derivatives on the biofilm mass were evaluated by using crystal violet assay. Ciprofloxacin, meropenem, ceftazidime, gentamicin were used as reference substances.

Reported results demonstrate that all compounds displayed antibiofilm activity at the tested concentrations. Remarkable reduction in biofilm formation of P. aeruginosa was found after treatment with KVM-97, KVM-261 and KVM-262 in high concentration (5× MIC), biofilm inhibition activity were 84.3%, 90.5% and 83.3% respectively.

After a treatment with KVM-204 at 250 μg/ml (5× MIC) 76.6% of the preformed 24-hr biofilms were destroyed. Furthermore, compounds KVM-97, KVM-194, and KVM-261 in both concentrations showed potent antibiofilm activity against the P. aeruginosa, inhibition activity values being between 56.7 and 65.7%.

All tested compounds in dose-dependent manner exhibited pronounced inhibition activity against mature 5-days P. аeruginosa biofilm.

It was also observed that tested compounds show high antibiofilm activity in comparison to reference antimicrobials.

The aminopropanol derivatives may provide templates for a new group of antimicrobial agents and potential future therapeutics for treating chronic infections.

References

1. Pendleton JN, Gorman S.P., Gilmore B. F. Clinical relevance of ESKAPE pathogens // Expert. Rev. Anti Infect Ther - 2013 - N 11 (3). - P. 297-308.
2. Gabrielyan N. I., Gorskaya E. М., Romanova N. I., Tsirulnikova O. M. Hospital microflora and biofilms // Vestn. transplantology and artificial organs. - 2012. - No. 3. - P. 83-91.
3. Donlan R. M., Costerton J. W. Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms // Clin. Microbiol - 2002. - V. 15, N 2. - P. 167-193.
4. Barber K. E., Werth B. J., McRoberts J. P., Rybak M. J. A novel approach utilizing biofilm time-kill curves to evaluate the bactericidal activity of ceftaroline combinations against biofilm-producing methicillin-resistant Staphylococcus aureus // Antimicrob. Agents Chemother. - 2014 - V. 58, N 5. - P. 2989-2992.
5. Mihailescu R. High activity of fosfomycin and rifampin against methicillin-resistant Staphylococcus aureus biofilm in vitro and in an experimental foreign-body infection model // Ibid. - 2014 - V. 58, N 5. - R. 2547-2553.
6. Golub AV Bacterial biofilms - a new therapeutic goal? // Klin microbial antimicrobial chemist  2012.  T. 14, No. 1.  P.23-29.
7. Okuda K. Effects of bacteriocins is a methicillin-resistant Staphylococcus aureus biofilm // Antimicrob. Agents Chemother. - 2013. - V. 57, N 11. - P. 5572-5579.
8. Navarro G. Image-based 384-well high-throughput screening method for the discovery of skyllamycins a to c as a biofilm inhibitor and inducers of biofilm detachment in Pseudomonas aeruginosa // Ibid. - 2014. - V. 58, N 2. - P. 1092-1099.
9. De la Fuente-Nunez C. Effect of nitroxides on swarming motility and biofilm formation, multicellular behaviors in Pseudomonas aeruginosa // Ibid. - 2013. - V. 57, N 10. - P. 4877-4877.
10. Kuehl R. Furanone at subinhibitory concentrations enhances staphylococcal biofilm formation by luxus repression // Ibid. - 2009. - V. 53, N 10. - R. 4159-4166
11. Pat. for the invention No. 89570. 1- [4- (1-Adamantyl) -phenoxy] -3- (N-benzyl, N-dimethylamino) -2-piperonyl chloride / Short Yu.V., Maksimov Yu.M., Vrinchanu N. O. et al. - I have filed it. 17. 04. 08; Pubwished 10. 02. 10, Bull. No. 3
12. Pat. for the invention No. 109202. 1- [4- (1,1,3,3-tetramethylbutyl) phenoxy] -3- (N-benzylhexamethylenemines) -2-propanol chloride / Short Yu.V., Vrinchanu N.O., Dronova M. L., Smertenko OA - Received. 20.12.2013; Pubwished 07. 07. 2015; Bull No. 14
13. Determination of sensitivity of microorganisms to antibacterial preparations. Method. instructions of the MUK 4.2.18-90-04 // Klin. microbe antimicrobial chemist - 2004. - Vol. 6, No. 4. - P. 306-359.
14. O'Toole G.A. Microtiter dish biofilm formation assay // J. Vis. Exp. - 2011. - N 47. - P. 2437.
Published
2018-08-14
How to Cite
Dudikova, D. M., Suvorova, Z. S., Nedashkivska, V. V., Sharova, A. O., Dronova, M. L., & Vrynchanu, N. O. (2018). Antibiofilm activity of aminopropanol derivatives against Pseudomonas aeruginosa. Farmatsevtychnyi Zhurnal, (1), 93-100. https://doi.org/10.32352/0367-3057.1.17.12
Section
Pharmacology

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