Zarqa Private UniversityBiology 4223 – The Fungi Medical Mycology Prof. Khaled H. Abu-Elteen

Zarqa Private UniversityBiology Zarqa Private UniversityBiology 4223 – The Fungi4223 – The Fungi

Medical MycologyMedical Mycology

Prof. Khaled H. Abu-ElteenProf. Khaled H. Abu-Elteen


Fungal DiseasesFungal Diseases

Mycosis- fungal infectionMycosis- fungal infection < 100 cause human disease< 100 cause human disease Not highly contagiousNot highly contagious Humans acquire from natureHumans acquire from nature

Groups based on degree on tissue Groups based on degree on tissue involvement and mode of entryinvolvement and mode of entry

Cutaneous mycoses-Cutaneous mycoses-dermatophytesdermatophytes Epidermis, hair & nailsEpidermis, hair & nails Contagious-direct or indirect contactContagious-direct or indirect contact Secrete keratinase that degrades Secrete keratinase that degrades keratinkeratin


Cutaneous MycosesCutaneous Mycoses Tinea( worm) capitis –blisters with scaly Tinea( worm) capitis –blisters with scaly

ringring Ringworm of the scalp Ringworm of the scalp

Spreads circularly forming bald spotsSpreads circularly forming bald spots Spread by contact with fomites , cats Spread by contact with fomites , cats

and dogsand dogs Tinea cruris-Tinea cruris- ringworm of groin ringworm of groin Tinea pedisTinea pedis - athlete's foot - athlete's foot


Systemic MycosesSystemic Mycoses Dimorphic fungiDimorphic fungi

Yeast form is invasiveYeast form is invasive Can spread throughout bodyCan spread throughout body Usually caused by fungi in soilUsually caused by fungi in soil Inhalation of sporesInhalation of spores Begins in lungs and spread to rest of Begins in lungs and spread to rest of

bodybody Not contagious person to personNot contagious person to person


IntroductionIntroduction

Obligate Parasitic Fungi Obligate Parasitic Fungi (dermatophytes)(dermatophytes): evolved to attack the : evolved to attack the outer surface of humansouter surface of humans

Facultative soil fungi:Facultative soil fungi: thermal thermal dimorphic saprobes, adaptations to dimorphic saprobes, adaptations to human bodyhuman body

Opportunistic saprobesOpportunistic saprobes: attack people : attack people with compromised immune systemswith compromised immune systems



Fungal InfectionsFungal Infections Superficial infections: involve Superficial infections: involve

outermost layers of skin and its outermost layers of skin and its appendages [ nails or hair] appendages [ nails or hair] ( Dermatophytosis)( Dermatophytosis)

Cutaneous infectionsCutaneous infections: involve deeper : involve deeper layers of skin causing allergic or layers of skin causing allergic or inflammatory responseinflammatory response

Subcutaneous infections: Subcutaneous infections: fungi with low fungi with low virulence, localized infection, or spread by virulence, localized infection, or spread by mycelial growthmycelial growth



Systemic infectionsSystemic infections: caused by : caused by true pathogenic fungi or true pathogenic fungi or opportunistic saprobesopportunistic saprobes


MycosesMycoses: diseases cause : diseases cause by fungiby fungi

SuperficialSuperficial Cutaneous Cutaneous SubcutaneousSubcutaneous SystemicSystemic OpportunisticOpportunistic


The SituationThe SituationFrequency

- most common fungal pathogen worldwide- 4th leading causes of nosocomial infections, 40% mortality- significant mortality and morbidity in low birth-weight infants- affects 75% women, 45% experience recurrence

> 10 million visits/year- classified as a STD by CDC

Immunocompromised- cancer and HIV-AIDs patientsC

- most commonly manifested in patients with leukemia or HIV-AIDs infections. Oral candidiasis is often a clue to acute primary infectionC

Public Concerns- increasing resistance to drug therapies due to antibiotics and antifungals


FUNGALFUNGAL DISEASESDISEASES

Mycosis:Mycosis: Any fungal disease. Tend to be chronic Any fungal disease. Tend to be chronic

because fungi grow slowly. because fungi grow slowly.

Mycoses are classified into the following categories:Mycoses are classified into the following categories:

I. Systemic mycoses: Fungal infections deep within the I. Systemic mycoses: Fungal infections deep within the

body. Can affect a number if tissues and organs.body. Can affect a number if tissues and organs.

Usually caused by fungi that live in the soil and are Usually caused by fungi that live in the soil and are

inhaled. Not contagious.inhaled. Not contagious.

Examples:Examples:

Histoplasmosis (Histoplasmosis (Histoplasma capsulatumHistoplasma capsulatum): ):

Initial infection in lungs. Later spreads Initial infection in lungs. Later spreads

through blood to most organs.through blood to most organs.

Coccidiomycosis (Coccidiomycosis (Coccidioides immitesCoccidioides immites): ):

Resembles tuberculosis.Resembles tuberculosis.


Systemic Mycosis: HistoplasmosisSystemic Mycosis: Histoplasmosis

Disseminated Histoplasma capsulatum, lung infection.


FUNGALFUNGAL DISEASES (Continued)DISEASES (Continued)

II. Cutaneous mycoses: Fungal infections of the skin, II. Cutaneous mycoses: Fungal infections of the skin,

hair, and nails. hair, and nails. Secrete keratinase, an enzyme that degrades Secrete keratinase, an enzyme that degrades

keratin.keratin. Infection is transmitted by direct contact or contact Infection is transmitted by direct contact or contact

with infected hair (hair salon) or cells (nail files, with infected hair (hair salon) or cells (nail files,

shower floors).shower floors). Examples:Examples:

Ringworm (Ringworm (Tinea capitisTinea capitis and and T. corporisT. corporis)) Athlete’s foot (Athlete’s foot (Tinea pedisTinea pedis)) Jock itch (Jock itch (Tinea crurisTinea cruris))


Opportunistic Infection by Opportunistic Infection by Candida Candida albicansalbicans in an AIDS Patient in an AIDS Patient


Severe nail infection with Trichophyton rubrum ina 37-year-old male AIDS patient.


Disseminated Histoplasma capsulatum, skin infection.


Cutaneous MycosisCutaneous Mycosis

Ringworm skin infection: Tinea corporis


Cutaneous MycosisCutaneous Mycosis

Candida albicans infection of the nails.



III. Subcutaneous mycoses: Fungal infections beneath III. Subcutaneous mycoses: Fungal infections beneath

the skin. the skin. Caused by saprophytic fungi that live in soil or on Caused by saprophytic fungi that live in soil or on

vegetation. vegetation. Infection occurs by implantation of spores or Infection occurs by implantation of spores or

mycelial fragments into a skin wound. mycelial fragments into a skin wound. Can spread to lymph vessels. Can spread to lymph vessels.

IV. Superficial mycoses: Infections of hair shafts andIV. Superficial mycoses: Infections of hair shafts and

superficial epidermal cells. Prevalent in tropical superficial epidermal cells. Prevalent in tropical

climatesclimates..



Opportunistic mycoses: Caused by organisms that are Opportunistic mycoses: Caused by organisms that are

generally harmless unless individual has weakened generally harmless unless individual has weakened

defenses:defenses:

AIDS and cancer patientsAIDS and cancer patients Individuals treated with broad spectrum Individuals treated with broad spectrum

antibioticsantibiotics Very old or very young individuals Very old or very young individuals

(newborns).(newborns). Examples:Examples:

Aspergillosis: Inhalation of Aspergillosis: Inhalation of AspergillusAspergillus spores. spores. Yeast Infections or Candidiasis: Caused Yeast Infections or Candidiasis: Caused

mainly by mainly by Candida albicansCandida albicans. Part of normal . Part of normal

mouth, esophagus, and vaginal flora.mouth, esophagus, and vaginal flora.


Cutaneous InfectionsCutaneous Infections

Dermatophytic hyphomycetesDermatophytic hyphomycetes 40 species40 species EpidermophytonEpidermophyton (2 species) (2 species) MicrosporumMicrosporum (17 species) (17 species) TrichophytonTrichophyton (24 species) (24 species) 50% of dermatophytes human 50% of dermatophytes human

specificspecific



Cause common tinea (ringworm)Cause common tinea (ringworm) Grow only on humansGrow only on humans Reservoir not in soil or animalsReservoir not in soil or animals Reservoir in carpets and upholstery Reservoir in carpets and upholstery

for up to two yearsfor up to two years



Trichophyton Trichophyton rubrumrubrum

Chronic Chronic infections of the infections of the toe nailstoe nails


Tinea corporisTinea corporis

Subcutaneous mycoses Subcutaneous infections - over 35 Subcutaneous infections - over 35

species produce chronic inflammatory species produce chronic inflammatory disease of subcutaneous tissues and disease of subcutaneous tissues and lymphatics. e.g. sporotrichosis - lymphatics. e.g. sporotrichosis - ulcerated lesions at site of inoculation ulcerated lesions at site of inoculation followed by multiple nodules - caused by followed by multiple nodules - caused by a dimorphic fungus: a dimorphic fungus: Sporotrix schenckii.

http://www.doctorfungus.org/mycoses/human/sporo/sporotrichosis.htm

http://www.doctorfungus.org/mycoses/human/sporo/sporotrichosis.htm



Microsporum canisMicrosporum canis Reservoir in catReservoir in cat May move to humans or dogsMay move to humans or dogs Dies out after one or two person-Dies out after one or two person-

person transfersperson transfers



Disease processDisease process Fungus stimulates epithelial cells of Fungus stimulates epithelial cells of

skin to divide more frequentlyskin to divide more frequently Makes more keratin available to Makes more keratin available to

fungusfungus Some species race specific in Some species race specific in

humanshumans Some species body location specificSome species body location specific



Candida albicans – candidiasis Candida albicans – candidiasis Normal component of gut mycotaNormal component of gut mycota Excessive wetness Excessive wetness overgrowth overgrowth

on skinon skin Vaginal candidiasis common in Vaginal candidiasis common in

pregnant womenpregnant women



Biology of Biology of Candida Candida albicansalbicans

Commensal Pathogen

A thin-walled dimorphic fungus

MorphogenesisUnicellular yeast (harmeless)Filamentous (pathogenic)

Principal Cell Wall PolymersGluccanMannan

Strict aerobe, favors moist surfacesCommensally found in gut, genitals, and lungsBody Temp 37º C, neutral pH

Figure 1. Yeast in Oral ScrapingA sample of an oral scraping contains yeast cells and pseudohyphae(www.doctorfungus.org)

Rapid Multiplication & Spread


Diseases by Diseases by C. albicansC. albicans

ThrushThrush

EsophagitisEsophagitis

Cutaneous CandidiasisCutaneous Candidiasis

Genital Yeast InfectionsGenital Yeast Infections

Deep CandidiasisDeep Candidiasis


Figure 1. Angular chelitis

Figure 2. Oral Thrush, atrophic Figure 3. Oral Thrush, pseudomembranous

Oropharyngeal Thrush

* Pseudomembranous

* Atrophic

* Angular chelitis

Symptoms

Risk FactorsHIV

Treatment: topical antifungals


Genital Yeast Candidiasis

Symptoms

Risk Factors- disruption of normal microbiota

Treatment- direct genital administration- tablets, suppositories, creams

Figure 1. Vaginal Yeast Culture

Figure 2. Plasma cell balanitis. A band-like infiltrate of plasma cells is in the dermis of the male penis.


Deep Candidiasis

Figure 1. Four forms of invasive candidiasis (www.doctorfungus.org)


PathogenesisHost Recognition

Adhesins

EnzymesHydrolases: Phosphoplipases, Lipases, Proteinases

MorphogenesisYeast form to Filamentous hyphae/pseudohyphae

Phenotypic Switching


Figure 1. skin equivalent before infection

Figure 2. Infection with pathogenic clinical isolate of C. albicans. After 48 h the yeast penetrates the skin equivalent and destroys the tissue

Figure 3. Infection with non-pathogenic C. albicans. This strain is not able to penetrate into the tissue and thus behaves as avirulent as shown in the mouse model of systemic infection.

Virulence assay of different C. albicans strains using the skin equivalent (AST 2000)

(Fraunhofer, 2002)


MORPHOGENESIS

Figure 2. Morphogenic forms of Candida albicanshttp://cbr-rbc.nrc-cnrc.gc.ca/thomaslab/candida/caindex.html

Figure 1. Morphogenesis.Morphogenesis in C. albicans is a pivotal virulence factor that allowsrapid multiplication andsubsequent disseminationin host tissue.(www.kent.ac.uk)


Subcutaneous InfectionsSubcutaneous Infections

Fungal ActivityFungal Activity Fungi normally saprobicFungi normally saprobic Introduced through woundsIntroduced through wounds Adapt to the human animal by Adapt to the human animal by

changes inchanges in morphologymorphology physiologyphysiology



ChromoblastosisChromoblastosis Common among barefoot peoples of Common among barefoot peoples of

the tropicsthe tropics Soil hyphomycete speciesSoil hyphomycete species Enters human by thorns or wood Enters human by thorns or wood

sliversslivers Fungus grows Fungus grows host cells respond host cells respond

by rapid cell division by rapid cell division wart-like wart-like growths on feet or legsgrowths on feet or legs



Mycotic MycetomaMycotic Mycetoma Disease of barefoot tropical peopleDisease of barefoot tropical people Entry: wound on footEntry: wound on foot Attacks Attacks various tissuesvarious tissues

Stimulates formation of tumorStimulates formation of tumor Compact fungal colonies form Compact fungal colonies form

within tumorwithin tumor



Skin ruptures Skin ruptures and some and some colonies extrudecolonies extrude


Systemic MycosesSystemic Mycoses

IntroductionIntroduction Caused by . . . Caused by . . .

Specialized pathogensSpecialized pathogensDimorphicDimorphic

One form outside the hostOne form outside the hostAnother form inside the hostAnother form inside the host

Opportunistic saprobesOpportunistic saprobes



Dimorphic Pathogen MycosesDimorphic Pathogen Mycoses HistoplasmosisHistoplasmosis

Histoplasma capsulatumHistoplasma capsulatumGrows on bird droppings, chicken Grows on bird droppings, chicken manure, bat guanomanure, bat guano

Conidia inhaled Conidia inhaled primary lung primary lung infection infection almost always fatal almost always fatal until recentlyuntil recently



Histoplasma Histoplasma capsulatumcapsulatum



CoddidioidomycosisCoddidioidomycosis Coccidioides immitisCoccidioides immitis Dry, saline soilsDry, saline soils Endemic to SW deserts of North Endemic to SW deserts of North

AmericaAmerica Valley feverValley fever Until recently – almost always fatalUntil recently – almost always fatal



Infection, disease process, and Infection, disease process, and clinical symptoms similar to clinical symptoms similar to histoplasmosishistoplasmosis

Can be effectively treated with Can be effectively treated with fluconazolefluconazole


Opportunistic Opportunistic Pathogens/DiseasePathogens/Disease

GeneralGeneral Pathogens all grow well at 37CPathogens all grow well at 37C None cause disease in well individualsNone cause disease in well individuals Require breakdown in resistance Require breakdown in resistance

systemsystem Complication of diabetes, AIDS, Complication of diabetes, AIDS,

advanced cancer, sequel to steroid or advanced cancer, sequel to steroid or antibiotic treatmentsantibiotic treatments



ZygomycosisZygomycosis Species of ZygomycotaSpecies of Zygomycota

Rhizopus, Mucor, RhizomucorRhizopus, Mucor, Rhizomucor Rhinocerebral mycosisRhinocerebral mycosis

Spores enter through sinusesSpores enter through sinuses Grows rapidly outward to the eyes Grows rapidly outward to the eyes

and inward towards the brainand inward towards the brain



AspergillosisAspergillosis AspergillusAspergillus sp. sp. Bronchiopulmonary aspergillosisBronchiopulmonary aspergillosis

Mucus within the bronchi Mucus within the bronchi severe severe allergic reactionallergic reaction

AspergillomaAspergilloma Forms a mycelia ball in lung cavity Forms a mycelia ball in lung cavity

formed from earlier TBformed from earlier TB



Surgical intervention often requiredSurgical intervention often required Invasive aspergillosisInvasive aspergillosis

Severely debilitatedSeverely debilitated Immunosuppressed (AIDS)Immunosuppressed (AIDS)

Almost always fatal until recentlyAlmost always fatal until recently


AIDS and MycosesAIDS and Mycoses

AspergillosisAspergillosis Candidiases (Candidiasis seen in 2/3 Candidiases (Candidiasis seen in 2/3

of AIDS patientsof AIDS patients CryptococcosisCryptococcosis Zygomycosis Zygomycosis Esophogeal candidiasis and Esophogeal candidiasis and

cryptococcosis are strong indicators cryptococcosis are strong indicators of AIDSof AIDS


PRIMARY ANTI-FUNGAL PRIMARY ANTI-FUNGAL AGENTSAGENTS

1.1. Polyene derivativesPolyene derivatives Amphotericin BAmphotericin B NystatinNystatin

2.2. AzolesAzoles KetoconazoleKetoconazole FluconazoleFluconazole ItraconazoleItraconazole VoriconazoleVoriconazole



AzolesAzoles

There are a few rare There are a few rare serious side effects serious side effects from Itraconazole from Itraconazole and Fluconazoleand Fluconazole


5-5-fluorocytosinefluorocytosine(5-FC)(5-FC)

Interferes With RNA Interferes With RNA SynthesisSynthesis


MECHANISMS OF ACTIONMECHANISMS OF ACTION

PolyenesPolyenes

AzolesAzoles

GriseofulvinGriseofulvin

5 - FC5 - FC

Ergosterol in cell Ergosterol in cell membranemembrane

Interfere with Interfere with ergosterol synthesisergosterol synthesis

Forms a barrier to Forms a barrier to fungal growthfungal growth

Inhibits RNA Inhibits RNA synthesissynthesis

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Zarqa Private UniversityBiology 4223 – The Fungi Medical Mycology Prof. Khaled H. Abu-Elteen