Medically Important Eukaryotes (Fungi and Protists) PDF

Medically important eukaryotes (Fungi and Protists) Microbes: Phylogeny and medically important groups. - No pathogenic with Archaea. What are protists? à Eukaryal microbes that are not fungi. - Algae = photosynthetic protists. - Protozoa = chemoorganotrophic protists....

Medically important eukaryotes (Fungi and Protists) Microbes: Phylogeny and medically important groups. - No pathogenic with Archaea. What are protists? à Eukaryal microbes that are not fungi. - Algae = photosynthetic protists. - Protozoa = chemoorganotrophic protists. o Amoebae o Flagellates o Parasitic Protists Trypanosomes: parasitic flagellate protozoans - Sleeping sickness – Africa - Chagas disease – America - Leishmaniasis – Worldwide - Complex life cycles with arthropod vectors. - Antigenic variation o the glycoprotein composition is switched cyclically meaning the cell has 1 of 1000 options at any one time – vaccines are unrealistic proposition. - Few frugs o available drugs target aspects of metabolism that are of greater importance to parasite cells than host cells. Apicomplexans - All Apicomplexans are either inter- or intra-cellular parasites of animals. They include Plasmodium (malaria); Toxoplasma; Cryptosporidium, and Eimeria. - Diagnostics of obligate parasites must rely on microscopy, serology or nucleic acids - Vaccines and finding drug are diQicult. - What are fungi? - Eukaryotic - Saprophytic heterotrophs o No chlorophyll - Typically, aerobic o Some are anaerobic (e.g. saccharomyces and rumen fungi) - Cell walls common – no peptidoglycan o Chitin, beta-glucans and glycoproteins. - Reproduce by both asexual and sexual. - Single or multi celled microbes. o Single – celled (yeast morphology) o Filamentous and independent (e.g. typical mushrooms) o Filamentous and Mutualistic (e.g. Mycorrhizae). Fungal nutrition - Heterotrophic = energy from organic carbon sources. - Absorptive (saprophytic) nutrition = soluble nutrients. o Insoluble nutrient sources, such as dead plant matter, degraded outside the fungal cell by secreted enzymes. - Host-associations (symbiosis spectrum) o Plant mutualisms common (70% plants need mycorrhizae) o Plant parasitism common (fungal plant pathogens) o Animal commensals (공생) (rumen fungi, skin commensals) o Animal pathogens. Fungal morphologies - Fungi: ‘microbes’ that are typically multicellular and many can grow at macroscopic scale. - Fungi can have a large foraging (채집) range. - Long-distance nutrient foraging requires bug size and inter-cellular transport. - Long hyphal filaments require rigid cell walls. Eukaryal phylogeny - Where fungo goy with other organisms. - Fungi are closer to animals than to plants and most protists. o Which helps explain why fungal diseases are so diQicult to treat. Importance of fungi to animal health - Allergenic fungi and hypersensitivity. - Food spoilage fungi and mycotoxins. - Commensal and pathogenic fungi. Allergenic fungi and hypersensitivity. - Main genera causing problems: o Aspergillus o Penicillium o Alternaria o Cladosporium - Grow under damp conditions and make allergenic spores and volatiles. Food spoilage fungi and mycotoxins - Fungi can grow on and damage all types of foods. - Mycotoxins à dangerous. (life threatening) Mycotoxicosis - Acute: o Moderate-high levels toxin. o Specific, observable disease. - Chronic: o Low-moderate levels of toxin. o Weight loss, infertility, failure to thrive. - Mycotoxin-associated diseases: o Low-very low levels of toxin. o General immunosuppression, increased susceptibility to infectious disease. Commensal and pathogenic fungi – the discipline of medical mycology - Invasive mycoses – the big three o Candidiasis o Aspergillosis o Cryptococcosis - Superficial, cutaneous and subcutaneous o Mycoses – infect skin and underlying tissue. Superficial mycoses - Limited to the outer surface of hair or skin. - Infection of hair shafts known as Piedras. - Up to 20% of population may be infected. Prevented by good personal hygiene, treated with cleansing agents. - Economical impact, long fungistatic treatment regime. - Disease names o Seborrheic dermatitis (severe dandruQ) § Sebum → oleic acid inflammatory response o Pityriasis versicolor (flaky, discoloured skin patches) o Piedra (nodules on hair shaft) o Malassezia folliculitis (a fungal pimple) - Common fungal causes o Malassezia spp – a typical skin commensal. o Trichophyton spp - Treatment o good hygiene, topic antifungal o ketoconazole shampoo, zinc pyrithione shampoo selenium sulfide lotion - cytostatic Cutaneous mycoses: ringworm, tinea - Disease names: o Tinea corporis (ringworm of body) o Tinea capitis (ringworm on scalp) o Tinea pedis (athlete’s foot) o Tinea cruris (ringworm of groin, ‘jock itch’) - Common fungal causes o Microsporum spp. o Trichophyton spp. - Cutaneous mycoses are deeper than superficial, more discomforting. - Caused by Dermatophytic fungi – eat skin keratin. - Very high carriage rates of casual organisms – easily passed via infected surfaces. - Usually treatable. Clinical aspects of cutaneous mycoses - Blister-like lesions dry to leave scaly ring. - Without treatment may get hair loss, change of hair colour, local inflammatory reactions. - Can be highly adapted to humans or transmitted from animals or via soil. - Treat by changing environment or by topical antifungal agents. Subcutaneous mycoses - Deep tissue. - Caused by numerous soil fungi, especially black moulds; introduced via puncture wounds; not spread from person to person. - Disease develops very slowly with fungi spreading along lymphatic channels. o Fungal tumour. - Diagnosis is important as some infections mimic subcutaneous mycoses. - Treatment: Generally diQicult; - some respond to antifungals; may require surgical excision. Summary of superficial, cutaneous and subcutaneous mycoses Invasive Fungal Infections (IFIs) - Few fungi can cause IFIs, and these are mostly rare or geographically confined. - The big three of global importance are: - All have increased because of increasing numbers of immunocompromised hosts. IFIs cause big problems in sick people Aspergillus – Aspergillosis - Primarily Aspergillus fumigatus (~85%) and Aspergillus flavus (~5%); other Aspergillus spp. ~5% - Acquired from the environment as Aspergillus makes millions of tiny spores - Aspergillosis is an opportunistic infection – gets more serious with the level of immunocompromise of the host. o Aspergilloma (fungus ball) (TB) o Invasive pulmonary aspergillosis § Similar to bacterial pneumonia o Disseminated aspergillosis § Crossing blood-brain-barrier. IFIs: Candidiasis - Candida albicans and other candida species cause candidiasis. - Single celled yeast that often forms pseudohyphae - A common cause of bloodstream infections in hospitals - Many Candida spp. are commensal so: o Can be acquired endogenously, or o Can be passed from person to person. Candidiasis takes many forms. Cryptococcosis - Caused by Cryptococcus species in two medically important species complexs: o Cryptococcus neoformans species complex o Cryptococcus gattii species complex - Grows as a yeast with a large capsule, which is an important virulence factor. o Thick polysaccharide coat (chitosan) o No longer virulent if removed. - Cryptococcosis o cryptococcal pneumonia o cryptococcal meningitis Process of cryptococcal infection - Acquired from the environment (tree hollows, soil, guano). - The first site of infection is the lungs. - From there it can disseminate to other parts of the body, particularly the brain – lipid rich. - People most at risk are patients with relatively severe immune defects. Summary of Big Three IFIs Diagnosis and treatment of fungal infections - Early and correct diagnosis and proper treatment are essentials. - Fungi not harmed by antibacterials or antivirals. Diagnosis and treatment of fungal infections - Diagnosis done by culture and microscopy. - Today, immunological and molecular techniques frequently used to speed up diagnosis – e.g. Antigen dipsticks, PCR, with fungus specific primers, MALDI-TOF Treatment with antifungal drugs - There are few eQective anti-fungal drugs. - Current drugs are grouped into 4 categories. - 1. Nucleic acid synthesis inhibitors (5-flucytosine) - 2. Ergosterol biosynthesis inhibitors (azoles, terbinifine) - 3. Polyenes (amphotericin B, nystatin) – fungicidal. - 4. Echinocandins (e.g. caspofungin) Treatment: Most antifungals target cell wall or membrane. Problems with antifungal drugs - There are few eQective anti-fungal drugs -