Understanding Fungal Diversity and Infections in Microbiology Lecture

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Explore the world of fungi and fungal infections in this informative microbiology lecture. Learn about common medically important yeasts, mold fungi, major fungal diseases, antifungal agents, and infection acquisition methods. Discover the different types of fungal infections, including superficial, cutaneous, subcutaneous, systemic, and opportunistic mycoses. Gain insights into hypersensitivity reactions, mycotoxicoses, and the impact on healthy versus immunocompromised hosts. Dive into primary systemic mycoses and opportunistic fungal infections in immunocompromised individuals.

  • Fungi Diversity
  • Fungal Infections
  • Microbiology Lecture
  • Mycoses
  • Immunocompromised

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  1. Lecture Title: Diversity of Fungi and Fungal Infections (Foundation Block, Microbiology) Lecturer name: Dr. Ahmed M. Albarrag Lecture Date: Oct-2013

  2. Lecture Objectives.. 1. To provide students with an overview of the common medically important yeasts and mold fungi. 2. To provide students with an overview of the major fungal diseases that threatens human health. 3. To give a fundamental knowledge about the antifungal agents, their mechanisms of action, and spectrum.

  3. Hypersensitivity (Allergy) Mycotoxicoses Infections

  4. How the infection is acquired? Endogenous, Colonization (overgrowth of normal flora) Inhalation (Airborne) Contact Trauma

  5. (When, which type of infection) Healthy host? OR Immunocompromised host?

  6. Superficial mycoses Cutaneous mycosis Subcutaneous mycoses Systemic mycoses Opportunistic mycoses

  7. Superficial Mycoses Affect the outer layer of the skin or hair shaft No immune response Cutaneous Mycoses Dermatophytosis Infection of the skin, hair or nails caused by a group of keratinophilic fungi, called dermatophytes

  8. Subcutaneous Mycoses Fungal infections involving the dermis, subcutaneous tissues, muscle and may extend to bone. Usually they are initiated by trauma.

  9. Primary Systemic Mycoses Caused by primary pathogens Contracted by inhalation, Start as respiratory disease Geographically restricted (endemic), north and south America 9

  10. Opportunistic fungal infections Diseases in immunocompromised host Risk factors HIV/AIDS Hematopoietic stem cell transplant (HSCT) Solid organs transplantation Malignancies Neutropenia Diabetes Many others

  11. The Fungi A) Opportunistic Fungi Normal flora Candida spp. Other yeast Ubiquitous in our environment Aspergillus spp. Zygomycetes spp. Cryptococcus spp. B) Primary Pathogens Dermatophytes Endemic geographically restricted - Histoplasma spp. - Blastomyces spp. -Coccidioides spp. -Paracoccidioides spp Other fungi

  12. Clinical features (history, risk factors, etc) Imaging Good value in diagnosis and therapy monitoring Lab Investigations Histopathology Microbiology

  13. Antifungal agents

  14. Cell membrane Polyene Azole Cell wall Echinocandins Caspofungin Micafungin Anidulafungin DNA/RNA synthesis Pyrimidine analogues - Flucytosine

  15. Amphotericin B, lipid formulations Nystatin Mechanism of Action Amphotericin B (MOA): Binds to ergosterol within the fungal cell membrane resulting in formation of pores which permit leakage of intracellular contents, and lead to death . Amphotericin B has an broad antifungal spectrum which includes most fungi that cause human disease

  16. Fluconazole Ketoconazole Itraconazole Voriconazole Posaconazole Miconazole, clotrimazole Mechanism of Action Inhibits synthesis of ergosterol, the major sterol of fungal cell membrane. Inhibits 14- -sterol demethylase, which is a microsomal CYP450 enzyme.

  17. Mechanism of Action Fungal RNA miscoding Interfering with DNA synthesis Spectrum of Activity (Restricted spectrum of activity) Active against Candida species Cryptococcus neoformans Monotherapy : now limited (Resistance)

  18. Caspofungin Micafungin Anidulafungin Mechanism of Action Inhibits B-1,3 D glucan synthase, the enzyme complex that forms glucan polymers in the fungal cell wall. Glucan polymers are responsible for providing rigidity to the cell wall. Good activity against Candida spp Aspergillus spp

  19. Target Group Mechanism of action Antifungal Agents Spectrum of activity Comments Cell membrane Polyenes Binds to ergosterol within cell membrane, formation of pores which lead to cell death Amphotericin B, Nystatin Broad antifungal spectrum which includes most fungi Serious toxic side effects (nephrotoxicity) Azoles Inhibit the synthesis of ergosterol Ketoconazole Itraconazole Fluconazole Voriconazole Posaconazole Miconazole clotrimazole Fluconazole has a limited or no activity against mould fungi Voriconazol is the drug of choice for Aspergillosis Posaconazole has broader spectrum of activity than other azoles Not effective against zygomycosis (except posaconazole) Adverse Effects Drug Interactions Inhibits glucan synthasis, (glucan polymers in the fungal cell wall) Cell wall Echinocandins Caspofungin Micafungin Anidulafungin Good activity against Candida spp ,Aspergillus spp Limited or no activity against other fungi Less toxicity and side effects compared to amphotericin B and azoles DNA/RNA synthesis Pyrimidine analogues Fungal RNA miscoding Interfering with DNA synthesis Flucytosine Restricted spectrum of activity Candida species Cryptococcus neoformans Monotherapy now limited (Resistance)

  20. Thank You (Foundation Block, Microbiology) Dr. Ahmed M. Albarrag Oct-2013

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