Fungi Flashcards
1
Q
Fungi Basic Characteristics
A
- Fungi are eukaryotic organisms (e.g., have a nucleus, membrane-bound organelles, linear DNA). Much more similar to animals and plants than to prokaryotic organisms like bacteria and archaea.
- Cell wall made of the following polysaccharides:
- Chitin
- β-glucan
- Mannan
- Cell membrane contains the sterol ergosterol
- Comparable function to cholesterol for mammalian membranes. Helps w/ fluidity and stabilization of the cell membrane.
2
Q
Fungi Uses in Human Society
A
- Edible
- Food production
- Ripening of cheese, leavening of bread
- Alcoholic beverages (e.g., yeast)
- Key to discovery/development of many pharmaceutical products especially antibiotics (e.g., penicillin is produced by the Penicillium species of fungus that kills bacteria). The majority of fungi are not pathogenic to humans, and are more frequently found as plant, insects, and amphibian pathogens.
- They also produce a variety of enzymes important to humans (e.g., Aspergillus produces asparaginase, amylase, and cellulase and Penicillium produces catalase))
3
Q
3 Major Categories of Pathogenic Fungi in Humans
A
- Yeasts
- Candida
- Cryptococcus
2. Molds
- Aspergillus
- Mucor spp
- Fusarium
3. Dimorphics - can switch between yeast/mold
- Histoplasma
- Coccidioides
4
Q
Yeasts
A
- Unicellular organism, 3-10μm (larger than most bacterial pathogens)
- Replicate by asexual budding or binary fission
- Can form pseudohyphae (strings of connecting, budding cells) or true hyphae (elongated cells)
- Examples:
- Candida spp
- Cryptococcal spp
5
Q
Molds
A
- Multicellular
- Comprised of nucleated filaments called hyphae, which together are called mycelium, and spores. To survive in harsh conditions, they upregulate the production of spores and the structures that release the spores are called conidia.
- They are involved in the decomposition of organic matter. When inhaled, they can cause allergies and asthma. They are also opportunistic pathogens in immunocompromised hosts.
- Examples
- Aspergillus spp
- Pseudallescheria spp
6
Q
Fungal Infections
A
- Superficial infections (tend to occur in healthy humans)
- Skin
- Mucous membranes
- Invasive/systemic infections, mainly in immuno-compromised patients. At risk populations include: HIV/AIDS, organ transplant patients, cancer patients undergoing chemotherapy, and extremes of age e.g., very young or very old.
- Pneumonia
- Meningitis
- Blood stream infections
7
Q
Trends in Fungal Infections
A
- The prevalence of invasive fungal infections has been increasing over time but the trends are varied depending on the fungal pathogen.
- Pneumosystis pneumonia and cryptococcosis peaked in the 1990s due to the HIV/AIDS epidemic and has been declining in the US ever since due to better treatments.
- Other fungal pathogens, including Candidemia and Invasive aspergillosis have been increasing.
8
Q
Superficial Fungal Infections
A
- Tinea corporis (Ring worm)
- Tinea pedis (Athlete’s foot)
- Tinea capitis (Cradle cap)
Cause by dermatophytes (e.g., trichophyton and microsporum)
Tend to infect people that are otherwise healthy and usually are easily treated with topical treatments
9
Q
Candida species
A
- Yeast – unicellular form
- 4 to 6 µM
- thin-walled, ovoid cells (blastospores) that reproduce by budding
- Form hyphae and pseudohyphae (important for pathogenesis)
- Culture: forms smooth, creamy white, glistening colonies
- Candida species are the most common cause of opportunistic fungal infections.
10
Q
Candida albicans
A
- A commensal organism
- Found in the GI tract, skin, lungs, and genitourinary tract of most people.
- Frequent cause of mucosal infections
- Oral (thrush)
- Skin (diaper rash)
- Genital (vaginal yeast infection)
- Fungemia (fungus in the blood) in immunocompromised patients
- C. albicans is also the most common species found among Candida
11
Q
Mucosal infections
A
- Caused by endogenous (exists within our own body) Candida that has overgrown
- Risk factors include:
- antibiotic use
- mucosal damage
- immune defect
- As those factors cause imbalance in normal biome of microorganisms.
12
Q
Thrush
A
- Oral candidiasis
- Infection of the mucous membranes of the mouth
- 50% of people are colonized with oral C. albicans
- When host immune system is compromised (e.g., HIV/AIDS) or at extremes of ages (i.e., babies)
- Treated with systemic (oral) or topical anti-fungal drugs
13
Q
Yeast Infections
also known as Candidal vulvovaginitis
A
- Candidal vulvovaginitis (medical term)
- Affects ~75% of women in their lifetimes
- Infection of vaginal mucous membranes
- Caused by overgrowth of the endogenous Candida present on the mucous membranes of the vagina.
- Symptoms: vaginal itching, pain, burning w/ urination, discharge
- Treatment: oral or topical anti-fungals
14
Q
Candida Bloodstream Infections
A
Pathogenesis
- Candidas ability to transition from a yeast cell to a hyphal (i.e. elongated) cell is critical to it becoming an invasive infection because it allows it to penetrate between cells/breach the mucosa and epithelium and into the bloodstream. Once in the bloodstream it can disseminate to other organs and cause infection to:
- Heart valves (endocarditis)
- Eye (endophthalmitis)
- Liver (hepatic abscess)
- Spleen (splenic abscess)
- Biofilms are also critical to Candida’s pathogenicity.
- Biofilms are dense communities of both yeast and hyphal cells. They are sticky and tightly adhere to a surface (usually catheters and any other foreign objects in the body) and are enclosed in an extracellular matrix. They are also metabolically inert.
- Biofilms are highly resistant to antifungals, and catheters must be removed to fully treat.
- Key risk factors:
- Immune defect
- Direct vascular access (indwelling catheter e.g., central venous catheter or hemodialysis catheter). C. albicans is the 3rd leading cause of catheter infections.
- Symptoms: Non-specific symptoms including fever, chills, low BP, fast heart rate. WILL NOT improve with antibiotics. The fact that antibiotics aren’t helping helps clue physicians in that it might be a fungal bloodstream infection.
- 3rd most common hospital-acquired bloodstream infection in US
- Mortality ~50% increased by the fact that physicians first assume a bacterial infection so may go untreated longer.
15
Q
Candida Virulence Mechanisms
A
- Morphogenetic change from yeast to hyphae is critical to its virulence.
- Inability to switch to hyphal cells prevents invasion/infection.
- Hyphal cells produce proteases, which help breakdown host tissue and get through epithelial layer, and also produce adhesin proteins, which help them adhere to surfaces and produce more biofilms.
- Not mentioned in slide, but formation of biofilms is clearly another important virulence factor.
16
Q
Other Candida Species
A
- C. albicans is the most common clinically
- Other species becoming more prevalent and drug resistant, including
- C. glabrata
- C. krusei
- C. auris
22
Q
C. neoformans Transmission
A
- Steps:
- Inhalation of spores. Common sources are soil, decaying trees, and pigeon excrement.
- Once inhaled, C. neoformans are phagocytized by alveolar macrophages. In healthy humans, macrophages usually kill the C. neoformans, but in immunocompromised hosts, some may survive the macrophages and live intracellularly, which is thought to be the source of the latent infection. C. neoformans can also survive extracellularly in the lung alveoli.
- Primary lung infection or establishment of latent infection
- Can spread from lung to CNS, leading to meningitis
- Causes 2 types of infection:
- Pneumonia
- Meningitis
24
Q
Epidemiology of C. Neoformans
A
- Main risk factor is a low CD4 count
- Opportunistic infection in HIV/AIDS
- In sub-Saharan Africa 20-80% of AIDS patients have cryptococcal infections
- ~1 million cases of cryptococcal meningitis per year
- High mortality rates in sub-Saharan Africa (50-70%)
28
Q
Cryptococcal Antigen (CrAg)
A
- ELISA
- Antibodies recognize and attach to the cryptococcal capsular antigens
- Then a secondary antibody that has a colored/fluorescent label attaches to that antibody-antigen complex , allowing for detection.
- Latex agglutination
- Capsular antigen-specific antibodies attached to latex beads
- Beads clump when mixed with Cryptococcus
30
Q
Aspergillus Fumigatus
A
- Most common pathologic species
- Most pathogenic (make you sicker)
- Found in soil, decaying vegetation, air, water
- Colonies: Smoky gray or green with a wooly texture
- Microscopy: roughened conidia 2-3.5 µm
- Hyphae are hylanie (lightly pigmented), have septa (have walls), and are usually branched at acute (typically 45 degrees) angles
32
Q
Aspergillus Clinical Manifestations
A
- Invasive Pulmonary Aspergillosis
- Most common form of aspergillus infections
- Most commonly seen in patients with neutropenia (low neutrophil counts), usually patients receiving chemotherapy. Neutrophils are non-specific immune cells that help combat infections
- Symptoms: progressive dry cough, dyspnea (difficulty breathing or feeling like you can’t catch your breath), pleuritic chest pain (pain when you take a deep breath), chest pain, fever despite broad spectrum antibiotics, and presence of pulmonary infiltrates
- Presents as a “halo” sign on CT due to the pulmonary infiltrates
- Allergic Bronchopulmonary Aspergillosis (ABPA)
- An allergic response to Aspergillus
- Seen in Cystic Fibrosis patients
- Clinical critieria
- asthma
- central bronchiectasis
- immediate skin test reactivity to Aspergillus
- elevated serum IgE
- elevated serum IgE and/or IgG antibody to A. fumigatus,
- fleeting infiltrates on chest radiography,
- serum precipitating antibodies to A. fumigatus, and
- peripheral blood eosinophilia
- Fungal Ball, also known as Aspergilloma
- A solid mass of hyphae growing in a previously existing pulmonary cavity
- Patients that present with this tend to have an underlying chronic disease that has led to the creation of a pulmonary cavity
- Relatively rare, and are either asymptomatic or if they have invaded the vasculature within the lungs they can cause fatal hemoptysis
- Treatment: Surgical excision
- Other invasive diseases:
- Sinusitis
- Cerebral Aspergillosis
- Bone Aspergillosis
- Skin Aspergillosis
