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Synergy Over Monotherapy

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Abstract

Pathogenic fungi, as an increasing global threat to human health, represent a sizable risk. However, significant attention should also be paid to the yeast biofilms. One promising strategy for combating resistant microbes, as well as fungal biofilms, is to extend the lifespan and efficacy of our currently employed drugs by using combination therapy. Since the application of combined therapy of fungal infections is currently accepted, we have decided to verify the efficacy of derivative H in combination with fluconazole on C. albicans biofilm. The main advantage of synergy over monotherapy lies in reducing or even completely preventing the induction of resistance of fungal cells. We have decided to verify the derivative H (1,4-dihydropyridine-2,3,5-tricarboxylate), an intermediate of nilvadipine synthesis, in the resistance of C. albicans to fluconazole. Therefore, we have focused on the influence of derivative H on the gene expression of the main C. albicans adhesin (ALS3), which is important for the tissue colonization during the infection process. Our results show that the newly synthesized derivative H had an impact on biofilm eradication. The effect of biofilm diminution could, therefore, be explained as derivative H preventing the adherence of C. albicans cells. This study supports even more the attractiveness of this substance as a potential agent that could be used in synergy with commonly used azoles to treat various fungal infections.

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References

  1. Shapiro RS, Robbins N, Cowen LE (2011) Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev 75(2):213–267. https://doi.org/10.1128/MMBR.00045-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Brown ED, Wright GD (2016) Antibacterial drug discovery in the resistance era. Nature 529(7586):336–343. https://doi.org/10.1038/nature17042

    Article  CAS  Google Scholar 

  3. Zimmermann GR, Lehár J, Keith CT (2007) Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today 12(1–2):34–42

    Article  CAS  PubMed  Google Scholar 

  4. Hill JA, Cowen LE (2015) Using combination therapy to thwart drug resistance. Future Microbiol 10(11):1719–1726. https://doi.org/10.2217/fmb.15.68

    Article  CAS  PubMed  Google Scholar 

  5. Chudík L, Marchalín Š, Daïch A, Decroix B (2000) New synthesis of the calcium antagonist Nilvadipine. Res Adv Synth Org Chem 1:1–7

    Google Scholar 

  6. Ježíková Z, Pagáč T, Pfeiferová B, Bujdáková H, Dižová S, Jančíková I, Gášková D, Olejníková P (2017) Synergy between azoles and 1,4-dihydropyridine derivative as an option to control fungal infections. Antonie Van Leeuwenhoek 110(9):1219–1226. https://doi.org/10.1007/s10482-017-0895-6

    Article  CAS  PubMed  Google Scholar 

  7. EUCAST (2017) European committee on antimicrobial susceptibility testing. http://www.eucast.org. Accessed Aug 2018

  8. Sherry L, Rajendran R, Lappin DF, Borghi E, Perdoni F, Falleni M, Tosi D, Smith K, Williams C, Jones B et al (2014) Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity. BMC Microbiol 14:182. https://doi.org/10.1186/1471-2180-14-182

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gullapalli S, Ramarao P (2002) L-type Ca2 + channel modulation by dihydropyridines potentiates kappa-opioid receptor agonist induced acute analgesia and inhibits development of tolerance in rats. Neuropharmacology 42(4):467–475. https://doi.org/10.1016/S0028-3908(01)00200-3

    Article  CAS  PubMed  Google Scholar 

  10. Whaley SG, Berkow EL, Rybak JM, Nishimoto AT, Barker KS, Rogers PD (2016) Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species. Front Microbiol 7:2173. https://doi.org/10.3389/fmicb.2016.02173

    Article  Google Scholar 

  11. Hoyer LL (2001) The ALS gene family of Candida albicans. Trends Microbiol 9(4):176–180

    Article  CAS  PubMed  Google Scholar 

  12. Zhao X, Daniels KJ, Oh SH, Green CB, Yeater KM, Soll DR, Hoyer LL (2006) Candida albicans Als3p is required for wild-type biofilm formation on silicone elastomer surfaces. Microbiology 152(8):2287–2299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nobile CJ, Mitchell AP (2006) Genetics and genomics of Candida albicans biofilm formation. Cell Microbiol 8(9):1382–1391

    Article  CAS  PubMed  Google Scholar 

  14. Nett JE, Lepak AJ, Marchillo K, Andes DR (2009) Time course global gene expression analysis of an in vivo Candida biofilm. J Infect Dis 200(2):307–313. https://doi.org/10.1086/599838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fanning S, Mitchell AP (2012) Fungal Biofilms. PLoS Pathog 8(4):e1002585. https://doi.org/10.1371/journal.ppat.1002585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Project APVV-0719-12 and VEGA Project 1/0697/18.

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Authors and Affiliations

  1. Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, 812 37, Bratislava, Slovakia

    Zuzana Ježíková, Tomáš Pagáč, Ján Víglaš, Barbora Pfeiferová & Petra Olejníková

  2. Comenius University Science Park, Comenius University, Mlynská dolina, Ilkovičova 8, 841 04, Bratislava, Slovakia

    Katarína Šoltys

  3. Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Mlynská dolina, Ilkovičova 6, 842 15, Bratislava 4, Slovakia

    Katarína Šoltys

  4. Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University, Mlynská dolina, Ilkovičova 6, 842 15, Bratislava 4, Slovakia

    Helena Bujdáková & Lucia Černáková

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  1. Zuzana Ježíková
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  2. Tomáš Pagáč
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  3. Ján Víglaš
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  4. Barbora Pfeiferová
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  5. Katarína Šoltys
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  6. Helena Bujdáková
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  7. Lucia Černáková
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  8. Petra Olejníková
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Correspondence to Zuzana Ježíková.

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Ježíková, Z., Pagáč, T., Víglaš, J. et al. Synergy Over Monotherapy. Curr Microbiol 76, 673–677 (2019). https://doi.org/10.1007/s00284-019-01678-9

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  • DOI: https://doi.org/10.1007/s00284-019-01678-9

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