fungal characteristics and human fungal...
TRANSCRIPT
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?