Candida albicans.pdf - Academic lab pages - School of Biosciences

Candida albicans

FUNGI & HUMANS• Live inextricably mycotic lives – bread, beer, wine etc• Inhabit our skin, mouth, GIT• Not all is harmony

C. albicans: Overview• First described in 1839 byBernard Langenbeck…microoganism – thrush• Christine Marie Berkhout,1923 - toga candida after whiterobe worn by Roman senatorsor senate candidates• Yeast belonging to familySaccharomycetaceae• Diploid fungi• Alternative morphology life• 2 nd to S. cereviciae in researchcoverage (PM 2010 hits: 25 Ca,11 Cn)Steven M et al (2009), NJMhyphaeyeast

C. albicans: Epidemiology• Commensal – mostly endogenic origin• Health care personnel• Accounts for 40 – 60% candidiasis cases• Intensive care units (ICUs) – 40-50% prevalence• Represent 4 th and 6 th nosocomial blood stream infections (BSI) inUS and Europe respectively• 8 th most common BSI in the UK• 1967 reports made on candida sp in 2007 representing 90% UKpopulation• Incidence rise attributed to increase in intensive care, greater useof invasive technologies, intravascular catheters, increasing use ofantibiotics and ….• ImmunocompromisationDerosa et al 2009, Minerva Anestesiol; Hassan et al 2009, J.Infect.

C. albicans: Pathology• Non-invasive candidiasis- Oral candidiasis (Thrush) or OPC- Vaginatis/vulvovaginal candidiasis- Diaper candidiasis (neonates)• Invasive candidiasis- candidemia- disseminated candidiasis -deeporgan involvement- Endocarditis- MeningitisDerosa et al 2009, Minerva Anestesiol; Shankar et al 2007, NeurologyIndia; CDCDFBMD

C. albicans: Diagnosis• Microscopy and culture – Standard• Serology – Detection of 48-kDA antigen(enolase) in candida species; 65-kDAmannoproteinprotein in C. albicans• Colometric assay - Detect β-D-glucan,major component of fungal cell wall• Latex agglutination – Detect manan, cellwall component• DNA detection testsBerzaghi et al 2009, Clin. & Vaccine Immunol.

C. albicans: TreatmentGeorgopapadakou et al 1994, Science

C. albicans: TreatmentGeneral approach to anti-fungal therapy in ICUShoham et al 2009, J. Intensve care Medicine

C. albicans: Pathogenesis• Diphorphism - unicellular yeast (blastospores & chlamydospores)or different filamentous forms (hypha, pseudo-hyphae)• Phenotypic switching (white Vs opaque colonies) - expression ofadherence proteins• Sexual mating – alpha forms more virulent• Chromatin modification – Histone acetylation (Rtt109)…. Survivalof RO killing by phagocytes• Immune evasion :- C. albican Pra1 binds Factor H (FH) and and FHL-1 to controland inactivate complement- Secreted aspartic proteases (Saps) also inactivate compliment- Pra1 binds & activates plasminogen to plasmin involved inextracellular matrix degradationJong et al 2001, Infect. & Immunity; Gropp et al 2009, Mol. Immuno.; Luo et al 2009,Mol. Immuno.; Lopes da Rosa et al 2009, Microbiol.

C. albicans: PathogenesisEndothelial barrier crossingTLR signaling – IF-γ, TNFα;pathogen recognitionLuo et al 2009, Mol. Immuno.; Grubb et al 2008, Infect. & Immunity

C. albicans: PathogenesisBMECmodelsPossible mechanisms of endothelial barrier crossingGrubb et al 2008, Infect. & Immunity

C. albicans: LessonsC. albicans C. neoformansPhylum Ascomycota BasidiomycotaFamily Sacchromycetaceae SporidiobolaceaeCell wall No capsule CapsuleBlood-brain barrier CrossCrossSexual life alpha forms alpha formsVirulence Dimorphism, Cell wall components Capsule, Cell wall components

C. albicans: TreatmentRussell Kightley Media: Scientific Illustration & Animation (ABN: 68 895 546882)