Integrated Pathways of Candida albicans Revealing Potential Targets and Key Factors Accountable for Pathogenicity

  • Sonali Mishra
  • Imlimaong Aier
  • Pritish Varadwaj
  • Krishna Misra
Research Article


Candida albicans is one of the most opportunistic commensal fungus of human biome found normally in gastrointestinal cavity of healthy humans. Its dimorphic character provides the easy switching of yeast to filamentous form. However, in immunocompromised patients, blood-stream infections often cause death, despite the use of anti-fungal therapies. Its dimorphic and highly adaptive properties make it even more pathogenic in nature. The hyphal growth causes virulence in Candida. There are many different pathways or factors responsible for the same in Candida albicans. It is thus paramount to see the relationship between the pathways and the key factors of pathogenicity. The common factors can be used to inhibit more than a single pathway at the same time. In the present work, systems biology approach has been employed to summarize all the pathways and common factors leading to yeast to hyphal transition in Candida. The study provides new and potential targets essential for antifungal drug discovery which is highly required against drug resistance.


Candida albicans Pathways Ras1-pka pathway Filamentation 



The authors (S.M. and I.A.) are thankful to Ministry of HRD, Govt. of India for research fellowships.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest to publish this manuscript.


  1. 1.
    Cutler JE (1991) Putative virulence factors of Candida albicans. Annu Rev Microbiol 45(187–218):5Google Scholar
  2. 2.
    Fidel PL Jr, Sobel JD (1994) The role of cell-mediated immunity in candidiasis. Trends Microbiol 2:202–205CrossRefPubMedGoogle Scholar
  3. 3.
    Xiang MJ, Liu JY, Ni PH, Wang S, Shi C, Wei B, Ni YX, Ge HL (2013) Erg11 mutations associated with azole resistance in clinical isolates of Candida albicans. FEMS Yeast Res 13(4):386–393CrossRefPubMedGoogle Scholar
  4. 4.
    O’Neill East M, Henderson JT, Jevons S (1983) Tioconazole in the treatment of fungal infections of the skin. An international clinical research program. Dermatologica 166(Suppl 1):20–33 PMID: 6884560 CrossRefPubMedGoogle Scholar
  5. 5.
    Lackner TE, Clissold SP (1989) Bifonazole. A review of its antimicrobial activity and therapeutic use in superficial mycoses. Drugs 38(2):204–225 PMID: 2670516 CrossRefPubMedGoogle Scholar
  6. 6.
    Whaley Sarah G, Berkow Elizabeth L, Rybak Jeffrey M, Nishimoto Andrew T, Barker Katherine S, David Rogers P (2017) Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species. Front Microbiol. PubMedPubMedCentralGoogle Scholar
  7. 7.
    Song JL, Harry JB, Eastman RT, Oliver BG, White TC (2004) The Candida albicans lanosterol 14-alpha-demethylase (ERG11) gene promoter is maximally induced after prolonged growth with antifungal drugs. Antimicrob Agents Chemother 48(4):1136–1144CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Michael C, Lorenz Gerald RF (2001) The glyoxylate cycle is required for fungal virulence. Nature 412:83–86CrossRefGoogle Scholar
  9. 9.
    Prieto D, Román E, Correia I, Pla J (2014) The HOG pathway is critical for the colonization of the mouse gastrointestinal tract by Candida albicans. PLoS ONE 9(1):e87128CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Richardson MD (2005) Changing patterns and trends in systemic fungal infections. J Antimicrob Chemother 56(Suppl 1):5–11CrossRefGoogle Scholar
  11. 11.
    Harren K, Tudzynski B (2013) Cch1 and Mid1 are functionally required for vegetative growth under low-calcium conditions in the phytopathogenic ascomycete Botrytis cinerea. Eukaryot Cell 12(5):712–724. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Pannanusorn S, Ramírez-Zavala B, Lünsdorf H, Agerberth B, Morschhäuser J, Römling U (2014) Characterization of biofilm formation and the role of BCR1 in clinical isolates of Candida parapsilosis. Eukaryot Cell 13(4):438–451CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lermann U, Morschhäuser J (2008) Secreted aspartic proteases are not required for invasion of reconstituted human epithelia by Candida albicans. Microbiology 154:3281–3295CrossRefPubMedGoogle Scholar
  14. 14.
    Inglis DO, Sherlock G (2013) Ras signaling gets fine-tuned: regulation of multiple pathogenic traits of Candida albicans. Eukaryot Cell 12(10):1316–1325. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kitano H (2003) A graphical notation for biochemical networks. Biosilico 1:169–176CrossRefGoogle Scholar
  16. 16.
    Shannon P (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kitano H (2003) A graphical notation for biochemical networks. Biosilico 1:169–176CrossRefGoogle Scholar
  18. 18.
    Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Kohl M, Wiese S, Warscheid B (2011) Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol 696:291–303CrossRefPubMedGoogle Scholar
  20. 20.
    Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T (2011) Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27:431–432CrossRefPubMedGoogle Scholar
  21. 21.
    Mi H, Muruganujan A, Demir E, Matsuoka Y, Funahashi A et al (2011) BioPAX support in cell designer. Bioinformatics 27:3437–3438CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The National Academy of Sciences, India 2018

Authors and Affiliations

  • Sonali Mishra
    • 1
  • Imlimaong Aier
    • 1
  • Pritish Varadwaj
    • 1
  • Krishna Misra
    • 1
  1. 1.Indian Institute of Information TechnologyAllahabadIndia

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