Skip to main content
Search
Search
    Quick Search anywhere
    Quick search in Citations
Advanced Search
Skip main navigationClose Drawer MenuOpen Drawer Menu
Previous article
Next article
Original Communication

Cholecalciferol, Ergosterol, and Cholesterol Enhance the Antibiotic Activity of Drugs

Published Online:July 09, 2019https://doi.org/10.1024/0300-9831/a000268

Abstract

Abstract. Background: This is the first report demonstrating the antibiotic-modifying activity of cholecalciferol. Aim: In this study, cholecalciferol was evaluated against multiresistant strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Methods: The antibacterial and modulatory effects of cholecalciferol, ergosterol, and cholesterol (8–512 μg/mL) were evaluated by microdilution assay against multiresistant bacterial strains. Results: Cholecalciferol, when combined with aminoglycosides, was more effective against P. aeruginosa, reducing the concentration of amikacin and gentamicin necessary to inhibit bacterial growth from 156.25 to 39.06 μg/mL and from 39.06 to 9.76 μg/mL, respectively. It is possible that cholecalciferol, due to its lipid-soluble nature, had a lipophilic interaction with the cell membrane, enhancing antibiotic uptake. Cholesterol and ergosterol were used to see if the mechanism of action of cholecalciferol was similar to that of these lipid compounds. Ergosterol and cholesterol increased aminoglycoside activity, where the effect was greater with higher subinhibitory concentration of sterol. Conclusions: There is no reported study on the use of cholesterol and ergosterol as modulators of antibiotics or any other drug, making this the first study in this area highlighting the interaction between cholesterol, ergosterol, and cholecalciferol with regard to modifying aminoglycoside activity.

Literature

  • File Jr, T. M. (2000) Overview of resistancein the 1990s. Chest 2 (Suppl.), 3–9. First citation in articleCrossref, Google Scholar

  • Catão, R. M.R, Barbosa-Filho, J. M., Gutierrez, S. J. C., Lima, E. O., Pereira, M. S. V., Arruda, T. A. and Antunes, R. M. P. (2005) Evaluation of the antimicrobial activity about multiresistant samples of Staphylococcus aureus and Escherichia coli. RBAC 37, 247–249. First citation in articleGoogle Scholar

  • Piddoc, L. J. V. (2006) Multidrug-resistance efflux pumps? Not just for resistance. Nat. Rev. Microbiol. 4, 629–636. First citation in articleCrossref, Google Scholar

  • Coutinho, H. D. M., Costa, J. G., Lima, E. O., Falcão-Silva, V. S. and Siqueira-Júnior, J. P. (2008) Enhancement of the antibiotic activity against a multiresistant Escherichia coli by Mentha arvensis L. and chlorpromazine. Chemotherapy 54, 328–330. First citation in articleCrossref, Google Scholar

  • Oliveira, J. F. P., Cipullo, J. P. and Burdmann, E. A. (2006) Aminoglycoside nephrotoxicity. Braz. J. Cardiovasc. Surg. 21, 444–452. First citation in articleGoogle Scholar

  • Coutinho, H. D.M, Costa, J. G., Lima, E. O., Falcão-Silva, V. S. and Siqueira-Júnior, J. P. (2010) Increasing of the aminoglicosyde antibiotic activity against a multidrug-resistant E. coli by Turnera ulmifolia L. and chlorpromazine. Biol. Res. Nurs. 11, 332–335. First citation in articleGoogle Scholar

  • Pretto, J. B., Cechinel, V., Noldin, V. F., Sartori, M. R. K., Isaias, D. E. B. and Bella, C. A. Z. (2004) Antimicrobial activity of fractions and compounds from Calophyllum brasiliense (clusiaceae/guttiferae). Z. Naturforsch. 59, 657–662. First citation in articleCrossref, Google Scholar

  • Gibbons, S. (2004) Anti-staphylococcal plant natural products. Nat. Prod. Rep. 126, 263–277. First citation in articleGoogle Scholar

  • Nicolson, K., Evans, G. and Otoole, P. W. (1999) Potentiation of methicillin. Activity against methicillin-resistant Staphylococcus aureus by diterpenes. FEMS Microbiol. Lett. 179, 233–239. First citation in articleGoogle Scholar

  • Dantas, A. T. Duarte, A. L. B. P. and Marques, C. D. L. (2009) Vitamin D in rheumatoid arthritis and lupus erythematosus. Rev. Bras. Med. 10, 52–59. First citation in articleGoogle Scholar

  • Marques, C. D. L., Dantas, A. T., Fragoso, T. S. and Duarte, A. L. B. P. (2010) The importance of vitamin D levels in autoimmune diseases. Rev. Bras. Reumatol. 50, 67–80. First citation in articleCrossref, Google Scholar

  • Martineau, A. R., Timms, P. M. and Bothamley, G. H. (2011) High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet 377, 242–250. First citation in articleCrossref, Google Scholar

  • Muszkat, P., Camargo, M. B. R., Griz, L. H. M. and Lazaretti-Castro, M. (2010) Evidence-based non-skeletal actions of vitamin D. Arq. Bras. Endocrinol. MeTab. 54, 110–117. First citation in articleCrossref, Google Scholar

  • Ludke, M. C. M. M. and López, J. (1999) Fatty acids concentration and level of cholesterol in diets for humans and presence in swine carcasses. Ci. Rural. 29, 181–187. First citation in articleCrossref, Google Scholar

  • Leança, C. C., Passarelli, M., Nakandakare, E. R. and Quintão, E. C. R. (2010) HDL: the yin-yang of cardiovascular disease. Arq. Bras. Endocrinol. MeTab. 54, 777–784. First citation in articleGoogle Scholar

  • Santos, A. R. and Carvalho, H. F. (2001) Biomembranes. In: The Cell 2001 (Carvalho, H. F. E. and Recco-Pimentel, S. M., eds.), pp. 39–56, Manole, Barueri, Brasil. [in Portuguese] First citation in articleGoogle Scholar

  • Thevissen, K., Kathelijne, K. A., Ferket, I., François, E. J. A. and Cammue, B. P. A. (2003) Interactions of antifungal plant defensins with fungal membrane components. Peptides 24, 1705–1712. First citation in articleCrossref, Google Scholar

  • Loguercio-leite, C., Groposo, C., Dreschler-Santos, E. R., Figueiredo, N. F., Godinho, P. S. and Abrão, R. L. (2006) The particularity of being a fungus – I. Cellular components. Biotemas 19, 17–27. First citation in articleGoogle Scholar

  • Schaechter, M., Engleberg, N. C., Eisenstein, B. I. and Medoff, G. (2002) Microbiology: Mechanisms of the Infectious Diseases. Ed. 3. Guanabara Koogan, Rio de Janeiro, Brazil. First citation in articleGoogle Scholar

  • Tortora, G. J., Funke, B. R. and Case, C. L. (2008) Microbiology. Ed 8. ARTMED, Porto Alegre, Brazil. First citation in articleGoogle Scholar

  • Javadpour, M. M., Juban, M. M., Lo, W. C., Bishop, S. M., Alberty, J. B., Cowell, S. M. Becker, C. L. and Mclaughlin, M. L. (1996) De novo antimicrobial peptides with low mammalian cell toxicity. J. Med. Chem. 39, 3107–3113. First citation in articleCrossref, Google Scholar

  • Köhler, T., Pechére, J. C. and Plésiat, P. (1999) Bacterial antibiotic efflux systems of medical importance. Cell 56, 771–778. First citation in articleCrossref, Google Scholar

  • Lee, E. W., Chen, J., Huda, M. N., Kuroda, T., Mizushima, T. and Tsuchiya, T. (2003) Functional cloning and expression of emeA, and characterization of emeA, a multidrug efflux pump from Enterococcus faecalis. Biol. Pharm. Bull. 26, 266–270. First citation in articleCrossref, Google Scholar

  • Taleb-Contini, S. H., Salvador, M. J., Watanabe, E., Ito, I. Y. and Dionéia, C. R. O. (2003) Antimicrobial activity of flavonoids and steroids isolated from two Chromolaena species. Rev. Bras. Ci. Farm. 30, 403–408. First citation in articleCrossref, Google Scholar

  • Canton, M. and Onofre, S. B. (2010) Interference from extracts of Baccharis dracunculifolia DC, Asteraceae, on the activity of antibiotics used in the clinic. Braz. J Pharmacog. 20, 348–354. First citation in articleGoogle Scholar

  • Burt, S. (2004) Essential oils: their antibacterial properties and potential applications in foods-a review. Int. J. Food Microbiol. 94, 223–253. First citation in articleCrossref, Google Scholar

  • Sousa, E. O., Barreto, F. S., Rodrigues, F. F. G. and Costa, J. G. M. (2011) Antibacterial activity and interference of Lantana camara L. and Lantana montevidensis (Spreng.) Briq. in the resistance of aminoglycosides. R. Bras. Bioci. 9, 1–5. First citation in articleGoogle Scholar

  • Coutinho, H. D. M., Costa, J. G. M., Siqueira-Júnior, J. P. and Lima, E. O. (2008) In vitro anti-staphylococcal activity of Hyptis martiusii Benth against methicillin-resistant Staphylococcus aureus-MRSA strains. Braz. J. Pharmacog. 18, 670–675. First citation in articleCrossref, Google Scholar

  • Matias, E. E. F., Santos, K. K. A., Almeida, T. S., Costa, J. G. M. and Coutinho, H. D. M. (2010) Enhancement of antibiotic activity by Cordia verbenacea DC. Latin Am. J. Pharma. 29, 1049–1052. First citation in articleGoogle Scholar

  • Rodrigues, F. F. G., Costa, J. G. M. and Coutinho, H. D. M. (2009) Synergy effects of the antibiotics gentamicin and the essential oil of Croton zehtneri. Phytomedicine 16, 1052–1055. First citation in articleCrossref, Google Scholar

  • Sikkema, J., Bont, J. A. M. and Poolman, B. (1994) Interaction of cyclic hydrocarbons with biological membranes. J. Biol. Chem. 269, 8022–8028. First citation in articleCrossref, Google Scholar

  • Turina, A. V., Nolan, M. V., Zygadlo, J. A. and Perillo, M. A. (2006) Natural terpenes: self-assembly and membrane partitioning. Biophys. Chem. 122, 101–113. First citation in articleCrossref, Google Scholar

  • Hirayama, K. B., Speridião, P. G. L. and Fagundes, U. N. (2006) Long chained polyunsaturated fatty acids. Eletronic J. Ped. Gastroenterol. Nutr. Liver Dis. 10, 1–12. First citation in articleGoogle Scholar

  • Cria Saúde (2015) Vitamin D. available at < http://www.criasaude.com br/N3032/vitamina-d.html>, accessed at 06 – July – 2015. First citation in articleGoogle Scholar

  • Sartori, M. R. K. (2005) Antimicrobial activity of fractions and extracts and pure compounds from the flowers of Acmela brasilensis Spreng (Wedelia paludosa) (Asteraceae). 81 f. MSc. Thesis, Universidade Vale do Itajaí, Itajaí – SC. First citation in articleGoogle Scholar

  • Nostro, A., Blanco, A. R., Cannatelli, M. A., Enea, V., Flamini, G., Morelli, I., Roccaro, A. S. and Alonzo, V. (2004) Susceptibility of methicillin-resistant staphylococci to oregano essential oil, carvacrol and thymol. FEMS Microbiol. Lett. 230, 191–195. First citation in articleCrossref, Google Scholar

  • Knowles, J. R., Roller, S., Murray, D. B. and Naidu, A. S. (2005) Antimicrobial action of carvacrol at different stages of dual-species biofilm development by Staphylococcus aureus and Salmonella enterica Serovar Typhimurium. Appl. Environ. Microbiol. 71, 797–803. First citation in articleCrossref, Google Scholar

  • Armstrong, J. S. (2006) Mitochondria: a target for cancer therapy. Br. J. Pharmacol. 147, 239–248. First citation in articleCrossref, Google Scholar

  • Frézard, F. and Schettini, D., (2005) Liposomes: physicochemical and pharmacological properties, applications in antimony-based chemotherapy. Quim. Nova 28, 511–518. First citation in articleGoogle Scholar