Skip to main content

Signaling Mechanisms in Pathogenesis and Virulence of Candida albicans

  • Chapter
  • First Online:
Candida albicans: Cellular and Molecular Biology
  • 1704 Accesses

Abstract

Invasive fungal infections kill over 1.5 million people a year worldwide, and this number is on the rise due to increasing numbers of people living with compromised immunity, including the elderly, premature infants, transplant recipients, and cancer patients. Fungal pathogens, such as, Candida albicans rely on complex network of signal transduction pathways that allow fungus to not only survive in the human host but also contribute to its pathogenesis. This chapter will focus on the up-to-date information on the signaling pathways and downstream target proteins that contribute to C. albicans virulence, which has been obtained primarily through the analysis of null mutants or inference from genome annotation. However, before addressing these issues in detail, a brief introduction of the magnitude and the economic impact of the healthcare problems caused by fungal pathogens and the currently available treatment options are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alexander BD et al (2013) Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis 56(12):1724–1732

    Google Scholar 

  • Andersson SG et al (2003) On the origin of mitochondria: a genomics perspective. Philos Trans R Soc Lond B Biol Sci 358:165–177, discussion 177–179

    Google Scholar 

  • Aoyama K et al (2001) Genetic analysis of the His-to-Asp phosphorelay implicated in mitotic cell cycle control: involvement of histidine-kinase genes of Schizosaccharomyces pombe. Biosci Biotechnol Biochem 65(10):2347–2352

    Google Scholar 

  • Ascioglu S et al (2002) Defining opportunistic fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 34(1):7–14

    Article  CAS  PubMed  Google Scholar 

  • Bahn YS et al (2006) A unique fungal two-component system regulates stress responses, drug sensitivity, sexual development, and virulence of Cryptococcus neoformans. Mol Biol Cell 17:3122–3135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown GD et al (2012) Hidden killers: human fungal infections. Sci Transl Med 4(165):165rv13

    Google Scholar 

  • Buck V et al (2001) Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway. Mol Biol Cell 12(2):407–419

    Google Scholar 

  • Butler G et al (2009) Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459:657–662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calderone RA, Fonzi WA (2001) Virulence factors of Candida albicans. Trends Microbiol 9(7):327–335

    Google Scholar 

  • Calera JA, Calderone RA (1999) Flocculation of hyphae is associated with a deletion in the putative CaHK1 two-component histidine kinase gene from Candida albicans. Microbiology 145:1431–1442

    Article  CAS  PubMed  Google Scholar 

  • Calera JA et al (1999) Avirulence of Candida albicans CaHK1 mutants in a murine model of hematogenously disseminated candidiasis. Infect Immun 67:4280–4284

    CAS  PubMed  PubMed Central  Google Scholar 

  • Calera JA et al (2000) Defective hyphal formation and avirulence caused by a deletion of the CSSK1 response regulator gene in Candida albicans. Infect Immun 68:518–525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chandrasekar PH, Sobel JD (2006) Micafungin: a new echinocandin. Clin Infect Dis 42:1171–1178

    Article  CAS  PubMed  Google Scholar 

  • Chapeland-Leclerc F et al (2007) Differential involvement of histidine kinase receptors in pseudohyphal development, stress adaptation, and drug sensitivity of the opportunistic yeast Candida lusitaniae. Eukaryot Cell 6(10):1782–1794

    Google Scholar 

  • Chauhan N et al (2003) The SSK1 of Candida albicans is associated with oxidative stress adaptation and cell wall biosynthesis. Eucaryot Cell 2:1018–1024

    Article  CAS  Google Scholar 

  • Chauhan N et al (2006) Signalling and oxidant adaptation in Candida albicans and Aspergillus fumigatus. Nat Rev Microbiol 4(6):435–444

    Google Scholar 

  • Chauhan N et al (2007) The Ssk1p response regulator and Chk1p histidine kinase mutants of Candida albicans are hypersensitive to fluconazole and voriconazole. Antimicrob Agents Chemother 51(10):3747–3751

    Google Scholar 

  • Chen D et al (2005) Deletion of the SSK1 response regulator gene in Candida albicans contributes to enhanced killing by human polymorphonuclear neutrophils. Infect Immun 73:865–871

    Article  Google Scholar 

  • Clemons KV et al (2002) fos-1, a putative histidine kinase as a virulence factor for systemic aspergillosis. Med Mycol 40:259–262. doi:10.1080/mmy.40.3.259.262

    CAS  PubMed  Google Scholar 

  • Deresinski CC, Stevens DA (2003) Caspofungin. Clin Infect Dis 36:1445–1457

    Article  CAS  PubMed  Google Scholar 

  • Desai C et al (2011) Candida albicans SRR1, a putative two component response regulator gene, is required for stress adaptation, morphogenesis and virulence. Eukaryot Cell 10(10):1370–1374

    Google Scholar 

  • Du C et al (2006) The role of the sakA (Hog1) and tcsB (Sln1) genes in the oxidant adaptation of Aspergillus fumigatus. Med Mycol 44:211–218

    Article  CAS  PubMed  Google Scholar 

  • Fassler JS and West AH (2013) Histidine phosphotransfer proteins in fungal two-component signal transduction pathways. Eukaryot Cell 12(8):1052–1060

    Google Scholar 

  • Gabaldon T, Huynen MA (2004) Shaping the mitochondrial proteome. Biochim Biophys Acta 1659:212–220

    Article  CAS  PubMed  Google Scholar 

  • Grant CM (2001) Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions. Mol Microbiol 39:533–541

    Article  CAS  PubMed  Google Scholar 

  • Gray MW (1993) Origin and evolution of organelle genomes. Curr Opin Genet Dev 3:884–890

    Article  CAS  PubMed  Google Scholar 

  • Hagiwara D et al (2013) NikA/TcsC histidine kinase is involved in conidiation, hyphal morphology, and responses to osmotic stress and antifungal chemicals in Aspergillus fumigatus. PLoS One 8(12):e80881. doi:10.1371/journal.pone.0080881. eCollection 2013

  • Hancock LE, Perego M (2004) Systematic inactivation and phenotypic characterization of two-component signal transduction systems of Enterococcus faecalis V583. J Bacteriol 186(23):7951–7958

    Google Scholar 

  • Koretke KK et al (2000) Evolution of two-component signal transduction. Mol Biol Evol 17(12):1956–1970

    Google Scholar 

  • Kruppa M, Calderone R (2006) Two-component signal transduction in human fungal pathogens. FEMS Yeast Res 6(2):149–159

    Google Scholar 

  • Kruppa M et al (2003) The Chk1p of C. albicans and its role in the regulation of cell wall synthesis. FEMS Yeast Res 3:289–299

    CAS  PubMed  Google Scholar 

  • Kruppa M et al (2004a) The histidine kinases of Candida albicans: regulation of cell wall mannan biosynthesis. FEMS Yeast Res 4(4–5):409–416

    Google Scholar 

  • Kruppa M et al (2004b) The two-component signal transduction protein Chk1p regulates quorum sensing in Candida albicans. Eukaryot Cell 3(4):1062–1065

    Google Scholar 

  • Kumamoto CA (2011) Inflammation and gastrointestinal Candida colonization. Curr Opin Microbiol 14(4):386–391

    Google Scholar 

  • Lee JW et al (2011) Multiple roles of Ypd1 phosphotransfer protein in viability, stress response, and virulence factor regulation in Cryptococcus neoformans. Eukaryot Cell 10(7):998–1002. doi:10.1128/EC.05124-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li D et al (2002) Temporal expression of the Candida albicans genes CHK1 and CSSK1, adherence and morphogenesis in a model of reconstituted human esophageal epithelial candidiasis. Infect Immun 70:1558–1565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li D et al (2009) The Candida albicans histidine kinase Chk1p: signaling and cell wall mannan. Fungal Genet Biol 46(10):731–741

    Google Scholar 

  • Mascher T et al (2006) Stimulus perception in bacterial signal-transducing histidine kinases. Microbiol Mol Biol Rev 70(4):910–938

    Google Scholar 

  • Mavrianos J et al (2013) Mitochondrial two-component signaling systems in Candida albicans. Eukaryot Cell 12(6):913–922

    Google Scholar 

  • Mavrianos J et al (2014) Two-component histidine phosphotransfer protein Ypd1 is not essential for viability in Candida albicans. Eukaryot Cell 13(4):452–460

    Google Scholar 

  • Menon V et al (2006) Functional studies of the Ssk1p response regulator protein of Candida albicans as determined by phenotypic analysis of receiver domain point mutants. Mol Microbiol 62(4):997–1013

    Article  CAS  PubMed  Google Scholar 

  • Menon V et al (2008) Transcriptional profiling of the Candida albicans Ssk1p receiver domain point mutants and their virulence. FEMS Yeast Res 8(5):756–763

    Google Scholar 

  • Nagahashi S et al (1998) Isolation of CaSLN1 and CaNIK1, the genes for osmosensing histidine kinase homologues, from the pathogenic fungus, Candida albicans. Microbiology 144:425–432

    Article  CAS  PubMed  Google Scholar 

  • Nemecek J et al (2006) Global control of dimorphism and virulence in fungi. Science 312:583–588

    Article  CAS  PubMed  Google Scholar 

  • Nierman WC et al (2005) Genome sequencing of the pathogenic/allergenic filamentous fungus Aspergillus fumigatus. Nature 438:1151–1156

    Article  CAS  PubMed  Google Scholar 

  • Nishino K, Yamaguchi A (2002) EvgA of the two-component signal transduction system modulates production of the yhiUV multidrug transporter in Escherichia coli. J Bacteriol 184(8):2319–2323

    Google Scholar 

  • Odami T et al (1997) Mannosyl phosphate transfer to cell wall mannan is regulated by the transcriptional level of the MNN4 gene in Saccharomyces cerevisiae. FEBS Lett 420:186–190

    Article  Google Scholar 

  • Park SG et al (2000) Distinct physiological functions of thiol peroxidase isoenzymes in Saccharomyces cerevisiae. J Biol Chem 275:5723–5732

    Article  CAS  PubMed  Google Scholar 

  • Pfaller MA (2004) Anidulafungin: an echinocandin antifungal. Expert Opin Investig Drugs 13:1183–1197

    Article  CAS  PubMed  Google Scholar 

  • Pfaller MA, Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20(1):133–163

    Google Scholar 

  • Pfaller MA et al (2012) Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata. J Clin Microbiol 50(4):1199–1203

    Google Scholar 

  • Posas F et al (1996) Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 “two-component” osmosensor. Cell 86(6):865–875

    Google Scholar 

  • Puthiyaveetil S et al (2008) The ancestral symbiont sensor kinase CSK links photosynthesis with gene expression in chloroplasts. Proc Natl Acad Sci USA 105:10061–10066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh P et al (2004) SKN7 of Candida albicans: mutant construction and phenotype analysis. Infect Immun 72:2390–2394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Srikantha T et al (1998) The two-component hybrid kinase regulator CaNIK1 of Candida albicans. Microbiology 144:2715–2729

    Article  CAS  PubMed  Google Scholar 

  • Stover BH et al (2001) Nosocomial infection rates in US children’s hospital’s neonatal and pediatric intensive care units. Am J Infect Control 29(3):152–157

    Article  CAS  PubMed  Google Scholar 

  • Torosantucci AP et al (2002) Deletion of the two-component histidine kinase gene (CHK1) of Candida albicans contributes to enhanced growth inhibition and killing by human neutrophils in vitro. Infect Immun 70:985–987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vehreschild J, Cornely O (2006) Micafungin sodium, the second of the echinocandin class of antifungals: theory and practice. Future Microbiol. 1:161–170

    Article  CAS  PubMed  Google Scholar 

  • Wenzel RP (1995) Nosocomial candidemia: risk factors and attributable mortality. Clin Infect Dis 20:153–154

    Article  Google Scholar 

  • Wilson LS et al (2002) The direct cost and incidence of systemic fungal infections. Value Health 5(1):26–34

    Article  PubMed  Google Scholar 

  • Wisplinghoff H et al (2003) Nosocomial blood stream infections in pediatric patients in US hospitals: epidemiology, clinical features, and susceptibilities. Pediatric Infect Dis J 22(8):686–691

    Article  Google Scholar 

  • Wisplinghoff H et al (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39:309–317

    Article  PubMed  Google Scholar 

  • Yamada-Okabe T et al (1999) Roles of three histidine kinase genes in hyphal development and virulence of the pathogenic fungus, Candida albicans. J Bacteriol 181:7243–7247

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Neeraj Chauhan .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Chauhan, N. (2017). Signaling Mechanisms in Pathogenesis and Virulence of Candida albicans . In: Prasad, R. (eds) Candida albicans: Cellular and Molecular Biology. Springer, Cham. https://doi.org/10.1007/978-3-319-50409-4_14

Download citation

Publish with us

Policies and ethics