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Molecular targets of biofabricated silver nanoparticles in Candida albicans

Abstract

We have analyzed the expressions of genes which regulate Ras-cAMP-EFG1 and CEK1-MAPK pathways involved in yeast to hyphal form morphogenesis in Candida albicans. The expression profile of genes associated with serum-induced morphogenesis showed reduced expressions of genes involved in these pathways by the treatment with biofabricated silver nanoparticles. Cell elongation gene, ECE1, was downregulated by 5.1 fold by the treatment of silver nanoparticles. Expression of hyphal inducer gene, TEC1 was downregulated by 6.28 fold. Negative regulators of yeast to hyphal transition, TUP1 and RFG1 were downregulated by 2.45 and 5.43 fold, respectively. Current study suggests that silver nanoparticles affect gene expression and may subsequently reduce virulence in C. albicans. Targeting genes involved in virulence may be an acceptable novel treatment strategy for pathogenic fungal infections.

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References

  1. 1.

    Silva S, Rodrigues CF, Araújo D, Rodrigues ME, Henriques M. Candida species biofilms’ antifungal resistance. J Fungi. 2017;3:8.

  2. 2.

    McCarthy MW, Baker T, Satlin MJ, Walsh TJ. Antibacterial and antifungal agents: the challenges of antimicrobial-resistant infections in immunocompromised hosts. In: Management of infections in the immunocompromised host; 2018; 297–315. Springer, Cham, Switzerland.

  3. 3.

    Halbandge SD, Mortale SP, Karuppayil SM. Biofabricated silver nanoparticles synergistically activate amphotericin B against mature biofilm forms of Candida Albicans. Open Nanomed J. 2017;4:1–16.

  4. 4.

    Hwang IS, Lee J, Hwang JH, Kim KJ, Lee DG. Silver nanoparticles induce apoptotic cell death in Candida albicans through the increase of hydroxyl radicals. FEBS J. 2012;279:1327–38.

  5. 5.

    Radhakrishnan VS, Mudiam MK, Kumar M, Dwivedi SP, Singh SP, Prasad T. Silver nanoparticles induced alterations in multiple cellular targets, which are critical for drug susceptibilities and pathogenicity in fungal pathogen (Candida albicans). Int J Nanomed. 2018;13:2647.

  6. 6.

    Biswas S, Van Dijck P, Datta A. Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans. Microbiol Mol Biol Rev. 2007;71:348–76.

  7. 7.

    El-adly A, Shabana I. Antimicrobial activity of green silver nanoparticles against fluconazole-resistant Candida albicans in animal model. Egypt J Bot. 2018;58:119–32.

  8. 8.

    Jadhav A, Mortale S, Halbandge S, Jangid P, Patil R, Gade W, Kharat K, Karuppayil SM. The dietary food components capric acid and caprylic acid inhibit virulence factors in Candida albicans through multitargeting. J Med Food. 2017;20:1083–90.

  9. 9.

    Chang W, Li Y, Zhang L, Cheng A, Lou H. Retigeric acid B attenuates the virulence of Candida albicans via inhibiting adenylyl cyclase activity targeted by enhanced farnesol production. PLOS ONE. 2012;7:1–12.

  10. 10.

    Ali A, Jadhav A, Jangid P, Patil R, Shelar A, Karuppayil SM. The human muscarinic acetylcholine receptor antagonist, dicyclomine targets signal transduction genes and inhibits the virulence factors in the human pathogen, Candida albicans. J Antibiot. 2018;71:456.

  11. 11.

    Conti M, Beavo J. Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Ann Rev Biochem. 2007;76:481–511.

  12. 12.

    Maurice DH, Ke H, Ahmad F, Wang Y, Chung J, Manganiello VC. Advances in targeting cyclic nucleotide phosphodiesterases. Nat Rev Drug Discov. 2014;13:290–314.

  13. 13.

    Ding X, Cao C, Zheng Q, Huang G. The regulatory subunit of protein kinase A (BCY1) in Candida albicans plays critical roles in filamentation and white-opaque switching but is not essential for cell growth. Front Microbiol. 2016;7:1–12.

  14. 14.

    Birse CE, Irwin MY, Fonzi WA, Sypherd PS. Cloning and characterization of ECE1, a gene expressed in association with cell elongation of the dimorphic pathogen Candida albicans. Infect Immun. 1993;61:3648–55.

  15. 15.

    Csank C, Schröppel K, Leberer E, et al. Roles of the Candida albicans mitogen-activated protein kinase homolog, Cek1p, in hyphal development and systemic candidiasis. Infect Immun. 1998;66:2713–21.

  16. 16.

    Köhler JR, Fink GR. Candida albicans strains heterozygous and homozygous for mutations in mitogen-activated protein kinase signaling components have defects in hyphal development. Proc Natl Acad Sci USA. 1996;93:13223–8.

  17. 17.

    Leberer E, Harcus D, Broadbent ID, et al. Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans. Proc Natl Acad Sci USA. 1996;93:13217–22.

  18. 18.

    Kadosh D, Johnson AD. Induction of the Candida albicans filamentous growth program by relief of transcriptional repression: a genome-wide analysis. Mol Biol Cell. 2005;16:2903–12.

  19. 19.

    Murad AMA, Leng P, Straffon M, et al. NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. EMBO J. 2001;20:4742–52.

  20. 20.

    Vila T, Romo JA, Pierce CG, McHardy SF, Saville SP, Lopez-Ribot JL. Targeting Candida albicans filamentation for antifungal drug development. Virulence. 2017;8:150–8.

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Acknowledgements

SDH and S.M.K. are thankful to Prof. PanditVidyasagar, Former Vice Chancellor, SRTM University, Nanded for his kind support under the UGC innovative program. RP is thankful to DST PURSE program and UPE-II program of Department of Biotechnology SavitribaiPhule, Pune University for financial support.

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The authors declare that they have no conflict of interest.

Correspondence to Sankunny Mohan Karuppayil.

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