Medical Microbiology

Li Mei Department of Microbiology November, 2006 Chapter 17, 18

Medical Mycology ­­­Fungi Non­cellular Prokaryotic Eukaryotic microorganisms microorganisms microorganisms Introduction • Fungi are eukaryotic organisms, and each fungal cell has at least one nucleus enclosed by a nuclear membrane, endoplasmic reticulum, mitochondria, and secretory apparatus, they do not contain chlorophyll.

What is the relationship between Fungi and Humans? Morel n Widely exist n ~50,000 species, n Be beneficial to human p biodegradation p source of food p the preparation of food p antibiotics n Widely exist n ~50,000 species, n Be beneficial to human p biodegradation p source of food p the preparation of food p antibiotics • Be harmful to human – ~300 species, pathogenic for human – Mycoses Medically important fungi

• Ascomycetes • Basidiomycetes • Zygomycetes • Deuteromycetes Ascomycetes ­­Sexual reproduction: ascus, ascospores. Basidiomycetes

­­Sexual reproduction: basidiospores on a basidium (basidia). Basidiomycetes Zygomycetes p Sexual reproduction the fusion of haploid mating hypha to produce diploid zygospores p Asexual reproduction spores in stalked sporangia

Deuteromycetes

q Imperfect fungi, no recognizable form of sexual reproduction. q Many are of medical significance.

Aspergillus Penicillium I. Morphology Cocci 0.8 µm Bacilli 4­6 µm Spirochetes 8 ­ 10 µm A. Size: Viruses 0.08 µm B. Structure of the fungal cell: Fungi 10 – 15 µm p Cell wall chitin, proteins, polysaccharides, lipids p Cell membrane ergosterol, instead of cholesterol p Cytoplasma organelles p Nucleus p Capsule e.g.,Cryptococcus neoformans C. Two basic morphological forms – Yeast – Mold Yeast budding

• Monocellular fungi • Round or oval • Reproduce by budding / by fission • Pseudohypha, pseudomycelia

Pseudohypha Mold

• Multicellular fungi – Hypha – Spores Hypha – branching, threadlike filaments of fungi that elongate at their tips – Based on structure • septate hypha • coenocytic hypha – Based on function • Vegetative hypha • Aerial hypha • Reproductive hypha: aerial hypha that produce spores Mycelium – a dense interwoven mass of hypha

Aerial hyphae

Vegetative hyphae Spore the reproductive structure of fungi;

• Sexual spores • Asexual spores

Basidiospores Ascus with ascospores

zygospores • Asexual spores – Conidia – Thallospores – Sporangiospores • Macroconidia • Blastospores • Microconidia • Chlamydospores • Arthrospores Morphology of asexual spores

Blastospores

Macroconidia and Microconidia Morphology of asexual spores

Sporangium containing Arthrospores sporangiospores

Chlamydospores hypha spore Contrast between spores of fungi and that of bacteria

Spores of fungi Spores of bacteria

Resistance to heat: weak (killed at 60℃ 1 hr) Strong (survive at 100℃ for 1~2 hrs)

One hypha can produce One bacterium can only many spores. form one spore.

Reproductive form of Not a reproductive form for fungi bacteria D. Fungal Dimorphism Dimorphic fungi • Yeast form – Parasitic form / Tissue form – Cultured at 35­37 ℃ • Mold form – Saprophytic form – Cultured at 25℃

Dimorphic transition relates to fungi pathogenicity. Dimorphic fungi

(Blastomyces dermatitidis)

(Coccidioides immitis)

(Histoplasma capsulatum)

(Paracoccidioides brasiliensis) II. Culture

• Culture medium: Sabouraud’s agar (4% glucose, 1% peptone, 2% agar) • 22℃~28℃, pH 4~6;

• High moisture and O 2 ; • Fungal colony a. Yeast colony, e.g., Cryptococcus neoformans. b. Yeast­like colony, e.g., Candida albicans. c. Filamentous colony, e.g., mold Yeast colony

round, pasty/mucoid creamy, opaque Yeast­like colony

Candida albicans Filamentous colony

Penicillium colony Mold colony III. Resistance

• Resistant – drying, UV, disinfectants, acid, alkaline – tetracycline, penicillin, streptomycin. • Sensitive – Heat (killed at 60℃ for 1 hour). – phenol (1~3%), iodine (2.5%), formalin (10%). – amphotericin B, ketoconazole, fluconazole, itraconazole, griseofulvin, nystatin, etc. IV. Pathogenicity

Virulence factors e.g., capsules enzymes, such as keratinase mycotoxins Mycoses: 4 types

• Hypersensitivity – Allergen: hypha, spores, fungal products – Diseases: urticaria, rhinitis, asthma, allergic dermatitis n Mycotoxicosis mycotoxins ingested by human → poisoning. n Fungal toxins and tumors A. flavus → aflatoxin→ hepatoma. • Mycotic infection

• Superficial infection • Cutaneous infection • Subcutaneous infection • Systemic infection • Superficial infection • outermost layers of the stratum corneum of the skin; • cuticle of the hair shaft • Cutaneous infection • epidermis, hair and nails • Subcutaneous infection • dermis, subcutaneous tissues and muscles • Systemic infection • Initiate in the lungs I. Superficial mycoses

Pityriasis versicolor (Malassezia furur)

Tinea nigra II. Cutaneous mycoses Dermatophytosis

Tinea (Ringworm of the skin)

Tinea capitis Tinea corporis Tinea unguium Tinea barbae (dermatophyte onychomycosis)

Tinea pedis Tinea cruris “athlete’s foot” III. Subcutaneous Mycosis

Lymphocutaneous sporotrichosis showing more advanced, ulcerating lesions developing along the lymph system of the forearm Chromoblastomycosis (Fonsecaea pedrosoi) III. Systemic Mycoses (endemic mycoses)

Involve deep viscera specific organophilic May become widely disseminated geographically restricted to specific areas ­­­ endemicity III. Systemic Mycoses (endemic mycoses)

Blastomycosis; ­­ the southeastern and south central states of North America Coccidioidomycosis; ­­ the southwestern parts of the US, in Mexico, in Central America, and in parts of South America. Paracoccidioidomycosis; ­­ South and Central America Histoplasmosis; ­­ endemic in certain areas of the United States IV. Opportunistic fungi infection – Candidiasis • Candida albicans – Cryptococcosis • Cryptococcus neoformans – Aspergillosis • Aspergillus – Mucormycosis • Mucor – PCP • Pneumocystis carinii Candidiasis

Candida albicans • mucocutaneous infection • e.g., thrush, vaginitis • Organ infection • e.g., bronchitis, pneumonia, esophagitis, enteritis, endocarditis, septicemia, etc • CNS infection • e.g., meningitis • Allergic diseases thrush Cryptococcosis Cryptococcus neoformans

• Round, capsule, 3~5 µm • blood agar and Sabouraud’s agar at 25℃(nonpathogenic) 37℃(pathogenic) • yeast form colony Cryptococcus

• Saprophytic, widely exist in soil and pigeon feces。 • Opportunistic exogenous infection – Main portal of entry: lung – cryptococcal pneumonia – cryptococcal meningitis Aspergillosis

• Caused by Aspergillus – Pulmonary aspergillosis – Mycotoxicosis & cancer PCP Pneumocystis carinii üPathogen of PCP (Pneumocystis carinii pneumonia) üMajor cause of death among AIDS patients. Focus on • Definitions

– Fungi, hypha, mycelium, fungal spore, fungi dimorphism • Questions – How many types of mycotic diseases are there? What are they? – What are different between the bacterium and fungus? – What are different between the bacterial spores and fungal spores? – Try to describe the structure of multicellular fungi. – How many fungal colony types are there? What are they? – Describe relationship between fungi and Humans? – Briefly list the diseases caused by Cryptococcus neoformance and Candida albicans. – List the name of opportunistic pathogens of fungi.