Fungi

Fungal Characteristics andHuman Fungal Pathogens

Fungal Taxonomy

Domain EukaryaKingdom Fungi

[True Fungi = Eumycota]– Phylum Zygomycota– Phylum Basidiomycota– Phylum Ascomycota– Phylum Chytridiomycota– Phylum Deuteromycota [Imperfect Fungi]

Fungal Taxonomic Names

Phylum-mycota

Class-mycetes

Order-ales

Family-aceae

GenusSpecies

Fungal CharacteristicsHeterotrophsMainly terrestrialLack Chlorophyll

Dark HabitatsMultidirectional

Spore bearingThallus bodyTypes:

MushroomMoulds

Aerobic, multicelledYeast

FA, single cell

Cell wall = chitin, glucanCell membrane = ergosterolNucleus

Membrane boundDiploid chromosomes

CytoplasmSimilar to plantsDifferent ribosomal synthesisDifferent microtubule protein

ReproductionSexually (meiotic)Asexually (mitotic)

Nutritional Status

SaphrophytesScavengers, recycleNon living materials

ParasitesFeed off living materials

MutualistsSymbionic relationshipPrimarily seen with plants

Beneficial Uses of Fungi

YeastsBakingbrewing

Antibioticspenicillincephalosporin

Other Drugscyclosporin

Steroidshormones

(reproductive)

FoodscheesesBlue Roquefort

Experimentalmetabolicpathways studied

Parasitic Fungi Overview

Cause Disease DirectlyActual fungal growth in organism

Cause Disease IndirectlyAllergic reactionsToxin ingestion

Exhibit Dimorphism [M Y shift]Mould form (mycelial, filamentous)Yeast form (or spherule form)Change due to temperature, nutrients, CO2 levels

Mould and Yeast

Laboratory Methods to IdentifyDirect

Id organism in specimen fluidHyphae: aseptate, septateSpore: conidiospore, arthrospore, sporangiosporeYeast: size, thickness of walls, capsule +/-

CultureMedia such as Sabaurouds, BHI, Mycosal

TissueStains: KOH, Eosin, India ink

SerologyCF, IFA

Flourescence of fungi under UV light

Immunity

NormalSkin

pHFAFloraturnover

Respiratorycilia

AbnormalImmunocompromised

BurnHIVChronic DiseaseGCCCancersDMPost surgicalSplenectomized

Fungal Infection Locations

SuperficialCutaneousSubcutaneousSystemic

LungsOther organ systems

Opportunistic

Fungal Mould Reproduction

Sexual StateMeioticTeleomorphProduce spores (conidia)

Asexual StateMitoticAnamorphProduce spores (conidia)

Sexual Reproduction of Fungi

Sexual Reproduction

Sex organs called gametangiaDistinguishable male and femaleCan bear sex cells (gametes)Can bear sex nuclei (gamete nuclei)

HomothallicSingle mycelium can sexually reproduce

HeterothallicTwo mycelia are required for sexual reproduction

Reproductive Life Cycle

Growth of hyphaeTransverse fissure

FragmentationBreak off

SporesSexual or asexualDisseminateHelp in Id of fungus

Size, shape, color, number

Sexual Spores

ZygosporeZygomycetes

Sporangium

AscosporeAscomycetes

Ascus rupture

BasidosporeBasidiomycetes

Gill house of basidium, pinches off

Asexual SporesSporangiospores

From sac head area called sporangiumRupture to releaseZygomycetes

ConidiosporesFree spores, not enclosed in sacPinched off segmentsAscomycetes, Basidiomycetes, DeuteromycetesTypes

ArthrosporesChlamydosporeBlastosporePhialosporeMicroconidiaMacroconidiaPorospore

Yeast: Sacchromyces

Fungal Yeast Reproduction

Diploid Cell (via asexual reproduction)Plentiful foodHaploid cells fuse to create diploidMother cell will bud diploid daughter cells

Haploid Cell (via sexual reproduction)Starved, Undernourished environmentMeiotic division to create 4, 1n daughters4 daughter spores remain inside “mother”Released when favorable environment

Yeast on Sabauroud Agar

Phyla include most of the yeasts

Phyla include mushrooms, puff balls, shelf fungi, rusts, & smuts

Phyla include saphrophytic bread moulds and some pathogens

Phyla contain any fungus that has no known sexual repro state

Fungal Phyla for aquatic, marine

Human Mycoses

Fungal Diseases of the Skin

SporotrichosisSporothrix schenckii

Clinical CourseErythematous

Papulonodularulcerative

LymphocutaneousJoints

Ostearthritistenosynovitis

PulmonaryCNSDisseminated

Lymphatic organsGI

Dimorphic fungusReservoir: worldwide, tropicalTransmission: direct soil innoculationDX: Special StainsTX: Antifungals

Sporothrix yeast phase

Sporothrix infection

CANDIDIASISCandidia albicans

Candidiasis of MMOropharynxVulvovaginalCutaneous

Invasive CandidiasisJointsGI: liver, pancreasUrinary

Miscellaneous Chronic

Includes invasive areasCNSRespiratory

Neonatal (thrush)

Small yeastsReservoir: soil, food, nosocomialSource: Human commensalsAssociated with immunocompromisedDX: Id organismTX: Antifungals

Candidia

Candidia infections: histology

DERMATOPHYTOSISTinea / Ringworm

Tinea capitusTinea corporisTinea crurisTinea pedisTinea unguiumTinea favosum

UbiquitousDirect contactColonize keratin layersCause annular lesions with central clearingDX: ID organism on selective media or with skin scrapingsTX: Antifungals Trichophytan

MicrosporumEpidermophytan

Trichophyton

Microsporum sp.

Tinea / Ringworm presentation

Trichophytan barbarae

Human Mycoses

Fungal Infections of the Nervous System

CRYPTOCOCCUSCryptococcus neoformans

Encapsulated WorldwideOpportunisticInhalation of sporesVirulence:

Enzymescapsule

DX: Id organismTX: Antifungals

Local in lungsAcute = ARDSChronic = pneumonia

DisseminatedCNS meningitisCutaneous ulcersGI inflammation liver, gall bladder, stomachBone ostemyelitisHeart inflammation,allRenal abscessEye inflammation, all

Cryptococcus neoformansinfections

Cryptococcus in the brain

Human Mycoses

Fungal Infections of the Cardiovascular System

ZYGOMYCOSISRhizomucor, Rhizopus, AbsidiaZygomycetes groupSoil, decayOpportunisticInvades arteries causing embolusDX: Autopsy, Culture, HistopathTX: AntifungalsPX: usually fatal

RhinocerebralDMOrbital structuresInternal Carotid

PulmonaryNeutropenicdyspneahemoptysis

GIMalnutritionIntraabdominal abscess

CutaneousSkin trauma, burnsNecrotic lesions

Other areasBoneHeart

Rhizomucor, Rhizopus

Rhizomucor

Rhizopus

Human Mycoses

Fungal Infections of the Respiratory System

ASPERGILLOSISAspergillus sp. Allergic

BronchopulmonarySinuses and lungs

PulmonaryWithin paranchyma

InvasiveCNSBone osetomyelitisHeart endocarditisRenal abscessCutaneous

post op, sxCatheter placementBurn victims

Ear

Soil, decayInhalation of sporesOpportunistic

Pulmonary DzImmunocompromised

DX: Id organism in fluids, culture, histopathologyTX: AntifungalsPx: Mortality rate is 50-100%

Aspergillosis

Culture specimenInfections

Aspergillus histology

CoccidioidomycosisCoccidioides immitis

Dimorphic fungiWestern hemisphere in arid regionsInhalation of sporesSpores transform to spherulesDX: CF, RADS, Isolation, Direct IDTX: AntifungalsPX: 90% resolve spontaneously unless immunocompromised

AsymptomaticAcute

Respiratory: SOB, painSkin: rash

ChronicPulmonary Nodules

DisseminatedSkin: ulcerativeJoints: synovitisMeninges: hydrocephalusAny other organs

Internal liningsGIUrogenitalEndocrine

Coccidioidomyces

Coccidioides immitis: Spherules

Coccidiodes clinical presentation

ParacoccidioidomycosesParacoccidioides brasiliensis

AsymptomaticDormantReappear if immunocompromised

MMUlcerations of mouth and oropharynx

PulmonaryNodular infiltratesMimic TB

CutaneousUlcerativeInvasive to S.C.

DisseminatedGI: liverBonesCNSMale genitourinary tract

South AmericaSoil, decayed woodInhalation of blastoconidiaDX: Id organism in specimens, culture, histopathologyTX: AntifungalsPX: good if treated, possibility of relapse

Paracoccidioides

KOH

Microscopic Yeast Phase

Macroscopic

BLASTOMYCOSESBlastomyces dermatitidis

Dimorphic, heterothallic ascomyceteSC, SE US : Mississippi and Ohio River ValleysSource

Soil, rotting woodGrowth in feces of bats, birds

Inhalation of conidiaDX: Direct Id of fluid specimens, Culture, HistopathologyTX: AntifungalsPX: spontaneous resoluton, TxCNS infections

Asymptomatic50% of infections

Acute PulmonaryMimics bacterial infections

Chronic PulmonaryMimics bronchogeniccarcinoma

DisseminatedSkin: ulcerativeBones: long bones, lyticGenitourinary

Male: ducts, glandsOthers

CNSPericardiumGIAdrenal Gland

Blastomyces: Yeast Phase

HISTOPLASMOSISHistoplasma capsulatum

Dimorphic fungusSoilInhalation of microconidiaDX: Direct Id of fungi in specimen sample, histopathology, cultureTX: AntifungalsPX: most are self limited, Tx if respiratory and disseminated

Subclinical, benignAcute

Self limited, flu-like symptomsPulmonary: pneumonitis, calcificationPericarditisRheumatological: arthritis

Chronic Pulmonary ~ TBFibrosing Mediastinitis

Fibrous CT in mediastinumAffects surrounding structures

DisseminatedLymphadenitisRed bone marrow suppressionEndocarditisCNS: meningitis, cerebritisGI: ulcersSkin: rashGenitourinary of malesEyes: uveitis, chorioditis

Histoplasmosis

Histoplasmosis: Disseminated

Histoplasmosis

Culture Id

Clinical Presentation

Cytology

Human Mycoses

Environmental Moulds

Environmental ExposureMycotoxins

IngestionErgotism

– Claviceps– Rye products– Limb gangrene– Alpha adrenergic

blockadeAflatoxins

– Aspergillus– Peanut meal– carcinogens

Zearalenones– Fusarium– Estrogen like steroid– Precocious puberty

AllergicPrior ExposureRe-exposureRespiratory signs

CoughingWheezingSinus congestionRhinorrheaItchy noseSore throat

Psychotropic agents

PsilocybinPsilocinLysergic Acid Diethylamide

Not all toxins are bad…..

Penicillium sp.Griseofulvin

Antimycotic actionSystemic useDisrupts mitotic spindle by binding to microtubule protein

AntifungalsMacrolides:

Bind to ergosterol to disrupt osmotic integrity of plasma membraneAmphotericin B, Nystatin

AzolesBlock ergosterol and chitin synthesis by inhibiting cytochrome P-450 enzymes, causes accumulation of product that replaces ergosterolTopical and /or systemic: Oral, IV, intrathecal, suppositoryKetaconazole, Itraconazole, Fluconazole, Clotrimazole, Miconazole

Allylamines: Binds to enzyme involved with ergosterol synthesis, thereby blockingTerbinafine (Lamisil)

Pyrimidine AnalogsRNA incorporation in place of uracilDNA synthesis blockage by enzyme bindingFlucytosine fluracil (RNA) further metabolites for DNA action

MiscellaneousGriseofulvin: disrupts mitotic spindleOthers with unkown MOA that have antifungal functions

Haloprogin, Ciclopirox, Tolnaftate, KI

Fungal Disease Summary

ZygomycotaRhizopus, Rhizomucor

AscomycotaAspergillus, Blastomyces, Histoplasmosis, Dermatophytes: Trichophyton, Microsporum, Epidermophyton

DeuteromycotaSporothrix, (Para)Coccidioides, Candidia

BasidiomycotaCryptococcus

Questions?

Would you give an antibiotic to a person with a fungal infection?How would you prevent self exposure when working with a patient with a fungal disease?