Module 3.1. Introduction to Mycology 1-9.pdf

BIO 125 Chapter 3. INTRODUCTION TO MYCOLOGY o Cell wall has pathobiologic properties during infection: mediate attachment of the fungus to host cells bind to pattern recognition receptors on host cell membranes (e g. Toll-like receptors) stimulate innate immune responses activate the complement ca...

BIO 125 Chapter 3. INTRODUCTION TO MYCOLOGY o Cell wall has pathobiologic properties during infection: mediate attachment of the fungus to host cells bind to pattern recognition receptors on host cell membranes (e g. Toll-like receptors) stimulate innate immune responses activate the complement cascade provoke inflammatory reaction Release immunodominant Ags elicit cellular immune responses & diagnostic Abs Contain melanin (dematiaceous) protect fungi from host defenses; imparts a brown or black pigment to the fungal colony OUTLINE I. II. III. IV. V. VI. VII. Overview Basic Biology of Fungi a. Fungal Structure b. Fungal Pathogenesis Fungal Toxins & Allergies Laboratory Diagnosis Mycotic Infections a. Cutaneous b. Superficial c. Endemic/Systemic d. Opportunistic Antifungal Therapy Summary Ergosterol major membrane sterol; favorite target of antifungal drugs o Imidazole antifungals inhibit ergosterol synthesis eg. azole drugs (ketoconazole, voriconazole) o Polyene antifungals bind more tightly to ergosterol than cholesterol e g. Amphotericin B OBJECTIVES 1. Review the basic morphology of fungi hyphae, yeast, dimorphism 2.Discuss the basic biochemistry of fungal structures versus other organisms 3. Discuss the basic mechanisms of antifungal therapy Remember the morphological characteristics, classification (cutaneous, systemic, opportunistic), and geographical location. I. OVERVIEW Fungi represent a ubiquitous & diverse group of organisms Degrade organic matter main purpose Mycology study of fungi, which are eukaryotic organisms that evolved in tandem with the animal kingdom However, unlike animals, most fungi are nonmotile & possess a rigid cell wall Unlike plants, fungi are nonphotosynthetic Approximately 80,000 species of fungi have been described o Only 400 are medically important o <50 are responsible for more than 90% of the fungal infections of humans & other animals Mycoses refers to infections that are caused by fungi Most pathogenic fungi are exogenous o Their natural habitats being water, soil, & organic debris Candidiasis & dermatophytes o Mycoses with highest incidence o Caused by fungi that are frequent components of the normal human microbiota & highly adapted to survival on the human host II. BASIC BIOLOGY OF FUNGI Eukaryotic (true nucleus, 80S ribosomes, mitochondria) Heterotrophic nutrition/existence o They require carbon for existence, and they get it from other organisms. o Fungi have no chloroplast (& chlorophyll too! Hence not green in color) photosynthesis Medical Microbiology FEATURE Nucleus Mitochondria & ER Cell Membrane sterols Cell wall content FUNGI Eukaryotic Present Present ( ergosterol) BACTERIA Prokaryotic Absent Absent Chitin mostly Peptidoglycan Spores Dimorphism Interchange between being a mold & a yeast Metabolism Reproduction Yes Survival No Aerobic Aerobic or Anaerobic Growth MOST fungi exhibit aerobic respiration, although some are facultatively anaerobic (fermentative), & others are strictly anaerobic. hours minutes Table 1. Comparison of fungi & bacteria A. FUNGAL STRUCTURE Two basic forms: yeasts & molds Some species are dimorphic & capable of growth as a yeast or mold depending on environmental conditions, such as temperature or available nutrients no heterotrophic organisms Saprophytic or saprobic living on dead organic material (D.O.M.) Parasitic Symbionts Commensals Complex carbohydrate cell walls: Chitin, glucan, mannan o Chitin is the most important component of the cell wall Bio 125 Medical Microbiology Chapter 3. Introduction to Mycology 1 of 12 FEATURE Cellularity Mode of Reproduction Morphology YEASTS Usually unicellular Budding or by fission Single cell Cultural Characteristics Round, pasty, or mucoid colonies on agar MOLDS Multicellular Mitosis Hyphae, mycelium Filamentous, hairy, or wooly colonies Hyphae may produce specialized asexual reproductive elements (spore or conidia) Figure 2. Molds. Table 2. Comparison of yeasts & molds YEASTS Single cells Most yeasts reproduce by Budding When you say budding, you are looking at 2 cells one larger, one smaller (daughter cell) asymmetrical cell division o Initiated by a lateral or terminal protrusion of new cell wall growth that enlarges during mitosis o One or more replicated nuclei enter the nascent bud forms a septum separates from the parent cell o Some species produce buds that fail to detach & become elongated produces chains of elongated yeast cells called pseudohyphae usually soft, opaque, 1-3 mm in size, & cream colored Figure 1. Yeasts. The nipple-like structure is the bud. Figure 3. Septate hyphae & nonseptate hyphae Significance: In medical mycology, there will not be much cultural characteristics that will be discussed. But for diagnosis part for biopsy, it is important to know the morphology! . THERMAL DIMORPHISM Dimorphism (Sil & Andrianopoulos, 2015) o Is defined as the ability of a fungus to generate free-living vegetative cell types that are either yeast or hyphal/mold Temperature is one of the main host signals that initiate their conversion Thermal Dimorphism o Refers to the ability to exhibit a certain morphology depending on the temperature o At MOLDS o At YEASTS Examples: 1. The patient has a fungal infection that is a granulomatous lesion under the skin/ bone marrow (systemic infection). What would you find/expect to see in the biopsy? Since the tissue diagnosis follows the body temperature, you should look for the YEAST. If it is cultured in the lab, it will grow as MOLDS. MOLDS Reproduce through mitosis Occurs by the production of multicellular branching cylindrical tubules called hyphae Hyphae are extended by apical elongation due to the production of new cell wall growth at the hyphal tips Mycelium the mass of intertwined hyphae that accumulates during active growth Some hyphae are divided into cells by cross-walls or septa o Except members of the Order Mucorales that is RARELY septated o transverse walls (septate hyphae) compartmentalized o multinucleated (nonseptate hyphae) not physically compartmentalized Bio 125 Medical Microbiology 2. : skin is where there is a transition from body temperature & room temperature you can see the appearance of both yeasts & molds Essential for pathogenicity (Boyce & Andrianopoulos, 2015) o Need to develop adaptations to circumvent the effectiveness of host defense responses o Examples: 1. Some fungi switch to yeast cell form to avoid phagocytosis & the cytotoxic environment of the phagolysosomal system 2.Some have dimorphic switch from a yeast to a filamentous growth (molds) to facilitate tissue penetration during infection o Thus, dimorphic switching allows for the colonization of unique environmental niches within the host & the failure to switch almost always attenuates pathogenicity in these fungi Chapter 3. Introduction to Mycology 2 of 12 involve tumor promotion or progression activation of protooncogenes (c-MYC, c-Ha-RAS, Ki-RAS, and N-RAS) cause mutations in the tumor suppressor gene TP53 TP53 mutation Temperature-derived signals trigger dimorphic through signaling pathways morphological & transcriptional responses If you want to know more of the technicalities, please see Fig. 4 in the appendix for the model of the signaling pathways controlling dimorphic Fungi that have this ability include the endemic mycoses/systemic mycoses FUNGUS CLINICAL DISEASE Blastomyces dermatitidis & gilchristii Blastomycosis Histoplasma capsulatum Histoplasmosis Coccidioides immitis & posadasii Coccidioidomycosis Paracoccidioides brasilensis & lutzii Paracoccidiodomycosis Sporothrix schenckii Talaromyces schenckii formerly known as Penicillium marneffeii Emmonsia spp. Sporotrichosis Penicilliosis Lacazia loboi Lacaziosis More technical ito pero good to know na rin. Pinapasearch din naman kasi ni Doc yung mechanism of carcinogenesis ng aflatoxin. We simplified it for you. Feel free to skip! Lifted from a journal by Marchese et al. (2018) Emmonsosis Table 3. Thermally dimorphic fungi pathogenic to humans & mammals (Gauthier, 2017) *see Fig. 4 in the appendix for some illustration YEASTS MOLDS - Figure 7. Mechanism of oncogenicity of AFB1 Aflatoxin B1 is mainly metabolized in the liver through oxidase enzymes from the CYP450 superfamily. Upon action of these oxidases, AFB1 is converted in the reactive 8,9-epoxide. Itong epoxide na ito has a high binding affinity toward the DNA forming AFB-N7-Gua adduct DNA mutations CANCER. Other things na ginagawa ng formed epoxide ay: 1. conjugation w/ GSH w/c is vital for detoxification of AFB1 as a carcinogen; can also lead to high levels of ROS OXIDATIVE DAMAGE 2. epoxide can be converted to dialdehyde form which can be excreted through urine or magbind sa proteins 3. Binding to proteins or RNA dysregulation of normal cellular functions & inhibition of proteins, DNA, & RNA synthesis . B. FUNGAL PATHOGENESIS 2 Types of host response: Granulomatous or Pyogenic response Some can be detected by using skin tests for delayed hypersensitivity reaction Reduced cell-mediated immunity predisposes to disseminated disease cancer, post-chemotherapy, use of steroids, & autoimmune disease (e g. HIV) Medical mycology flourished as a branch of Microbiology beginning in the 1980s together with the emergence of HIV because many fungal infections are actually AIDS-defining illnesses III. FUNGAL TOXINS & ALLERGIES A. Amanita mushrooms Liver necrosis due to amanitin & phylloidin amanitin & phylloidin interfere with nucleotide synthesis kasi iniinhibit nya yung formation ng phosphodiester bonds. Fig 6. Amanita phylloides or death cup mushrooms. Not edible due to hepatotoxins amanitin or phylloidin Sample question (from Murray): A 42-year-old man in India ate homegrown maize for several days & started developing symptoms of hepatitis. The patient was eventually rushed to the hospital, where he died of acute hepatic failure. 1. What was the most likely cause of his acute liver failure? Aflatoxin 2. What organism was most likely responsible for this toxic illness? Aspergillus flavus 3. What are the long-term consequences of chronic low-level exposure to this mycotoxin? Hepatocellular carcinoma . B. Aspergillus flavus ingestion of contaminated peanuts and grains causes liver cancer due to aflatoxin Aflatoxin B1 o Most potent natural carcinogen o associated with both toxicity & carcinogenicity in humans & animals o primary mode of human exposure is through consumption of contaminated foods (peanuts & cereal grains) C. Aspergillus fumigatus normal household molds inhalation of the spores causes allergic bronchopulmonary aspergillosis (IgE-mediated) o Mechanism of oncongenicity of aflatoxin: Bio 125 Medical Microbiology Chapter 3. Introduction to Mycology 3 of 12 IV. LABORATORY DIAGNOSIS OF FUNGI A. MICROSCOPY microscopy of KOH preparation o KOH dissolves human cells allowing visualization Smear human tissue on the slide add KOH kasi yung smear mo pwedeng magkalo yung skin cells and yung fungal cells. Sometimes, the presence of human tissue can obscure the outline of the fungal cells. In microscopy, fungal cells are not in full watermark . o Addition of calcofluor white Nonspecific fungal cell wall stain Visible with a fluorescent microscope o Gently heating the slide dissolve excess tissue debris & inflammatory cells o Can also be observed in blood smears, CSF, & other preps treated with Gram or Wright stain If formalin-fixed biopsy specimens H&E B. MICROSCOPY Sabouraud's agar Dextrose Agar (SDA) o Contains glucose (carbon source) & modified peptone (pH 7.0) o Supports growth of fungi o Restricts growth of bacteria o Used for identification Add antibiotics to inhibit bacteria Add cycloheximide to inhibit saprobic/saphrophytic molds Potato Dextrose Agar stimulates production of conidia Low pH inhibits the growth of bacteria DNA probes for early infection tests for fungal antigens or antibodies to fungal antigens V. MYCOTIC INFECTIONS Superficial & Cutaneous mycoses among the most common of all communicable diseases Cutaneous mycoses caused by fungi that infect only the keratinized tissue (skin, hair, nails) Subcutaneous mycoses normally reside in soil or on vegetation; enter skin or subcutaneous tissue by traumatic inoculation with contaminated material Endemic mycoses/Systemic geographically restricted to specific areas of endemicity Opportunistic mycoses often infect immunocompromised individuals A. CUTANEOUS DERMATOPHYTOSES (RING WORMS) 3 important genera of dermatophytes: o Microsporum canis - septate hyphae, macroconidia, and microconidia. Macroconidia are spindle-shaped, with an asymmetrical apical knob o Trichophyton tonsurans - septate hyphae, numerous microconidia formed along the hyphae or on short conidiophores which grow perpendicular to the hyphae o Epidermophyton floccosum - septate, hyaline hyphae, smooth, thin-walled, club-shaped macroconidia and absence of microconidia Transmission: Direct contact, dogs and cats, shared fomites (inaminate object like towels) Ring worms is a misnomer; Figure 8. Microsporum canis (upper left), Trichophyton tonsurans (upper right) & Epidermophyton floccosum (lower). Illustrations from Jawetz can be found in the Appendix Table 4. Key fungal structures observed in microscopic examinations of clinical specimens. This will not be included by Doc Calderon in the exam, but he said that this might be helpful for other lectures; aid in familiarization of keywords to make a diagnosis SPECTRUM OF DISEASE Depends on anatomical location o Tinea pedis (athlete's foot) o Tinea unguium- nails o Tinea corporis -body o Tinea cruris (jock itch) crotch o Tinea manuum- hands o Tinea capitis- head o Tinea barbae- facial hair ; . Child has many B. SUPERFICIAL Bio 125 Medical Microbiology immunocompromised; Malnutrition most common cause of being immunocompromised Chapter 3. Introduction to Mycology 4 of 12 Inhaled microconidia (spores) develop into budding yeast inside macrophages Spreads to liver and spleen dissemination in those who have defective CMI (cell mediated immunity) Intracellular yeasts Malasezzia furfur (Tinea Versicolor) superficial skin infection of cosmetic importance For fair-skinned, not really visible. But once they get a tan, areas that are not tan an MYTH: An-an ay nakukuha sa chalk an- Hypopigmented areas Spaghetti and meatballs appearance on 10% KOH Selenium sulfide shampoo treatment In UST for our poor patients, head and shoulder. Figure 14. budding yeast inside macrophages Figure 10 Blastomyces dermatidis Chronic pneumonia Ulcerated Granulomas Lytic bone lesions Prostatitis Can be found in the same areas where you can find your histoplasma - Figure 11. Malassezia furfur. Spaghetti & meatballs C. SUBCUTANEOUS Sporothrix schenckii (SPOROTRICHOSIS) Dimorphic fungus that lives on vegetation occurs most often in gardeners/ florsists, especially those who prune roses Transmission: thorn prick o If patient was pricked, it can travel upwards axially or lymphatically. ASTEROID BODIES: hallmark of sporotrichosis Figure 12. Sporotrichosis D. SYSTEMIC/ENDEMIC INFECTIONS Coccidioides immitis arthrospores form spherules filled with endospores granulomata in bones and CNS dissemination in those who have defective CMI Coccidioides mycosis- disease Dimoprhic fungus: mold in air produces a spore (arthrospores) that you inhale which germinate to become yeasts. Figure 15. Blastomyces dermatidis. Yeast with a broad-based bud. Snowman appearance or figure of 8 D. Paracoccidioides brasiliensis Chronic pneumonia painful ulcers on mouth and nose Endemic only in South America Preferentially infect male o Female hormones are inhibitory o Man- Figure 17. The center is the mother yeast while the peripheral are the buds Bio 125 Medical Microbiology Figure 18. Painful ulcers on mouth & nose Please remember the geographical locations of each systemic/endemic infections & their tissue forms. According to Dr. Calderon, systemic infections are also described as endemic since the book is US-based. A table (Table 5. Summary of Systemic Infections) is provided in the Appendix for the myoses and their corresponding geographic distribution. Figure 13. This is the yeast with endospores inside. Histoplasma capsulatum Figure 16. Blastomycoses dermatidis lesion . Chapter 3. Introduction to Mycology 5 of 12 E. OPPORTUNISTIC MYCOSES Candida albicans IMMUNOCOMPETENT Oral thrush - those who did not gargle after puffing the steroids o Oral thrush vs. leukoplakia You can scrape off oral thrush In leukoplakia, you cannot scrape it off Vulvovaginitis - curd-like discharge Intertrigo found in Intertriginous areas. Rhizopus oryzae & Mucor spp. (Mucormycosis) Saprophytic molds with nonseptate hyphae with walls and branches at right angles Rhino-orbital-cerebral infection with eschar formation Patients with diabetic ketoacidosis, burns or leukemia Usual case: A woman with big breast and diabetes. Reddish lesions/satellite lesions in the borders of the breast. Diabetics have decreased gamma-globulin production predisposing you to infection. Skin infections - satellite lesions Onychomycosis IMMUNOCOMPROMISED Esophagitis Oral thrush - not an AIDS defining illness Candidial esophagitis AIDS defining Subcutaneous nodules Right-sided endocarditis VI. ANTIFUNGAL THERAPY Figure 19. Oral thrush (1st pic); vulvovaginitis (2nd pic); Esophageal Candidaiasis rd (3 pic) Cryptococcus neoformans Asymptomatic Lung Infection Meningitis Encephalitis expectoration of brownish bronchial plugs MNEMONIC Aspergillus Think A! Acute Angles in Aspergillus. Bio 125 Medical Microbiology Figure 22. Antifungal therapy. Squalene via Squalene Epoxidase Lanosterol via 14-Desmethyl Lanosterol Ergosterol Cholesterol. **Focus kayo sa MOA nung drugs. A. DRUGS FOR SYSTEMIC FUNGAL INFECTIONS AMPHOTERICIN B Remember that these fungi are eukaryotes and humans are also eukaryotes, so when you give drugs that has anti-eukaryotes expect mo rin na merong side effects. Example dito ay yung kay AmphoB tinatarget nya yung ergosterol sa fungal cell membranes, same din sa ergosterol sa cholesterol ng humans, so nasisira din yung cell membrane. One example of toxicity is Nephrotoxicity. Cryptococcus on India Ink Aspergillus fumigatus Infections o Wounds o Burns o Cornea o External ear o Sinuses Aspergilloma (fungus ball) in lung cavities Allergic Bronchopulmonary Aspergillosis (ABPA) o Asthmatic symptoms with Figure 21. Eschar formation Figure 20. Aspergilloma. Drug Class: Antifungal (polyene) MOA: FungiCIDAL o Binds to ergosterol in fungal cell membranes, alters permeability by forming artificial pores Toxicities: o Chills o Fever o Muscle spasms o Hypotension o Vomiting o Headache o Nephrotoxicity FLUCYTOSINE Drug Class: Antifungal (Pyrimidine antimetabolite) MOA: FungiSTATIC o Accumulated in fungal cells by the action of permease and converted by cytosine deaminase to 5-FU, which inhibits thymidylate synthase - Inhibits DNA synthesis o Clinical Use: Cryptococcosis Systemic Candidial Infection Chromoblastomycosis Chapter 3. Introduction to Mycology 6 of 12 o Toxicities Myelosuppresion Alopecia Hepatotoxicity Selective toxicity occurs because mammalian cells have low levels of permease and deaminase KETOCONAZOLE Drug Class: Antifungal (azole) MOA: FungiSTATIC o Inhibits fungal -demethylase (P450-dependent enzymes) blocking ergosterol synthesis Clinical Use: o Chronic mucocutaneous candidiasis o Dermatophytosis Toxicities o GI disturbance (vomiting diarrhea) o Rash o Hepatotoxicity o Drug interactions Narrow antifungal spectrum Potent CYP450 inhibition Limited to topical use because of systemic toxicity ITRACONAZOLE Drug Class: Antifungal (azole) MOA: FungiSTATIC o Inhibits fungal -demethylase (P450-dependent enzymes) blocking ergosterol synthesis Clinical use o Blastomycosis o Sporotrichosis o Dermatophytosis o Chromoblastomycosis o Alternative for infection due to Aspergillus, Coccidiodies, Cryptococcus, and Histoplasma Toxicities o GI disturbance (vomiting diarrhea) o Rash o Hepatotoxicity CASPOFUNGIN Drug Class: Antifungal (Echinocandin) MOA: Inhibit B-glucan synthase decreasing fungal cell wall synthesis Clinical Use: o Disseminated and mucocutaneous candidiasis o Salvage therapy for invasive aspergillosis o Empiric therapy during febrile neutropenia Toxicities o Headache o GI distress o Fever o Rash o Flushing (histamine release) o Elevated liver enzymes B. SYSTEMIC DRUGS FOR SUPERFICIAL MYCOSES GRISEOFULVIN Drug Class: Antifungal MOA: FungiSTATIC o Interferes with microtubule function. Inhibits synthesis and polymerization of nucleic acid Bio 125 Medical Microbiology Clinical Use: Dermatophytosis Toxicities: o Headache o Mental Confusion o GI Irritation o Photosensitivity o Hepatotoxicity o Disulfiram reaction o Accumulates in Keratin o Potent CYP450 inducer o C/I in porphyria TERBINAFINE Drug Class: Antifungal MOA: FungiCIDAL o Interfere with ergosterol synthesis by inhibiting fungal Squalene Epoxidase Clinical Use: o Dermatophytoses o Onchomycosis Toxicities: o GI upset o Rash o Headache o Taste Disturbances C. TOPICAL DRUGS FOR SUPERFICIAL FUNGAL INFECTIONS NYSTATIN Drug Class: Antifungal (polyene) MOA: fungicidal o Binds to ergosterol in fungal cell membranes forming artificial pores Clinical Use: o Candidiasis (Oropharyngeal, Esophageal, Vaginal) Toxicities o Nephrotoxicity Minimal mucocutaneous absorption CLOTRIMAZOLE Drug Class: Antifungal (azole) MOA: fungistatic o Inhibit fungal -demethylase (P450-dependent enzymes) blocking ergosterol synthesis Clinical Use: o Mucocutaneous Candidiasis o Dermatophytosis o Seborrheic Dermatitis o Pityriasis Versicolor Toxicities o Non-significant when administered topically o Limited to topical use because of systemic toxicity VII. SUMMARY Fungi are heterotrophic, non-photosynthetic organisms Fungi can cause disease in the immunocompetent, more so, in the immunodeficient individual Antifungal therapy is directed at inhibiting structures unique to fungi minimize the risk of adverse effects on human cells REFERENCES Jawetz Melnick & Adelbergs Medical Microbiology, 27 th ed (2016) Murray Medical Microbiology 7th ed (2013) Chapter 3. Introduction to Mycology 7 of 12 Boyce, KJ & A. Andrianopoulos. (2015). Fungal dimorphism: the switch from hyphae to yeast is a specialized morphogenetic adaptation allowing colonization of a host. FEMS Microbiol Rev. 39(6):797-811. Doi: 10.1093/femsre/fuv035. Retrieved on Feb. 11, 2020. Gauthier, G. (2017). Fungal dimorphism & virulence: molecular mechanisms for temperature adaptation, immune evasion, & in vivo survival. Mediators Inflammatory. Doi: 10.1155/2017/8491383. Retrieved on Feb. 11, 2020. Marchese, S., A. Polo, A. Ariano, S. Velotto, S. Costantini, & L. Severino. Aflatoxin B1 & M1: biological properties & their involvement in cancer development. Toxins (Basel). 10(6):214. Doi: 10.3390/toxins10060214. Retrieved on Feb. 11, 2020. Sil, A. & A. Andrianopoulos. (2015). Thermally dimorphic human fungal pathogens polphyletic pathogens with a convergent pathogenicity trait. Cold Spring Harbor Perspective Medicine. 5(8):a019794. Doi: 10.1101/cshperspect.a019794. Retrieved on Feb. 11, 2020. IMPORTANT COINS TO REMEMBER: Mycelium Room temperature Yeast Tissue (body temperature) To differentiate yeast and KOH hyphae Fungal non selective culture (SDA) Brown to black macules Hortaea werneckii (Tinea nigra) Budding yeast with hyphae Tinea versicolor Tinea versicolor Pityrosporum orbiculare Spaghetti and meatballs Bifurcated hyphae Skin, nails, and rarely hair Endothrix invasion Favus Rhinoorbital infection Yeast with a broad based bud Most common opportunistic fungi Common in AIDS Germ tube CHROMagar Encapsulated Cryptococcus neoformans IgE-mediated Hilar lymphadenopathy Brownish bronchial plugs Interfere with ergosterol synthesis by inhibiting squalene epoxidase Inhibits cell wall synthesis Interferes with microtubule function Inhibits DNA synthesis Interfere with ergosterol synthesis by inhibiting P450dependent enzymes Fungicidal and fungistatic Antifungal that can enter the CNS, for systemic infection Bio 125 Medical Microbiology Pityrosporum orbiculare Epidermophtyon Epidermophtyon T. violaceum T. schoenleinii Rhizopus Blastomyces dermatitidis Candida albicans Candidiasis Candida albicans Candida albicans Cryptococcus neoformans India ink Aspergillus Aspergillus Aspergillus Terbinafine Echinocandins Griseofulvin Flucytosine Azoles Ciclopirox Amphotericin B Chapter 3. Introduction to Mycology 8 of 12 APPENDIX Figure 5. Saprobic & parasitic phases of endemic dimorphic fungi. A. Histoplasma capsulatum, B. Blastomyces dermatitidis. C. Paracoccicodioides brasiliensis. D. Coccidioiodes immitis, E. Penicillium marneffei. Fig. 4 in the appendix for the model of the signaling pathways controlling dimorphic Table 5. Systemic/Endemic mycoses Bio 125 Medical Microbiology Chapter 3. Introduction to Mycology 9 of 12