What type of pathogen is Candida albicans and when does it cause disease?
- Commensal yeast on mucosa/skin
- Becomes an opportunistic pathogen when immunity or microbiota are disrupted (antibiotics, HIV, diabetes, catheters, neutropenia)
Candida albicans is typically harmless but can cause infections under certain conditions.
List three common clinical forms of candidiasis.
- Oral thrush (OPC)
- Vulvovaginal candidiasis (VVC)
- Invasive candidiasis/candidemia (bloodstream ± organs)
These forms represent different manifestations of Candida infections.
Name four key risk factors for invasive candidiasis.
- Neutropenia
- Central venous catheter / ICU stay
- Broad-spectrum antibiotics
- Major surgery/intestinal damage or immunosuppression
These factors increase the likelihood of developing invasive candidiasis.
What are the main virulence factors of C. albicans?
- Adhesins/invasins (ALS family, Hwp1, Als3)
- Morphogenesis (yeast ↔ hyphae)
- Biofilm formation
- Secreted enzymes (SAPs, phospholipases)
- Toxin candidalysin
These factors contribute to the pathogenicity of C. albicans.
Why is morphogenesis (yeast ↔ hyphae) important in Candida?
- Yeast: colonisation & dissemination
- Hyphae: tissue penetration, biofilm scaffolding, cell damage
- Switching allows adaptation between commensal and invasive lifestyles
This adaptability is crucial for survival in different environments.
What is candidalysin?
- A 31-aa peptide toxin derived from ECE1, secreted from hyphal tips
- Inserts into host membranes → pores, epithelial damage and inflammation
Candidalysin plays a significant role in the pathogenicity of C. albicans.
What does the Candida cell wall consist of (inner vs outer)?
- Inner: β-glucan + chitin → structural skeleton
- Outer: mannoproteins (N- and O-mannans) → adhesion, antigenic surface, immune evasion
The structure of the cell wall is critical for its function and interaction with the host.
What does Hwp1 do?
- Hyphal wall protein 1, GPI-anchored adhesin
- Substrate for host transglutaminase → covalent attachment to epithelial cells
- Crucial for stable adhesion and biofilm formation
Hwp1 is important for the establishment of infections.
What is the ALS family and what does Als3 do?
- ALS = Agglutinin-Like Sequence adhesins (ALS1–7, ALS9)
- Als3: hyphal adhesin & invasin, binds host cadherins → induces endocytosis; also ferritin receptor (iron uptake)
The ALS family plays a role in adhesion and invasion of host tissues.
What are SAPs and which SAPs are linked to mucosal vs systemic disease?
- SAPs: Secreted Aspartyl Proteinases (Sap1–Sap10) that digest host proteins
- Sap1–3: mucosal / cutaneous infections
- Sap4–6: systemic candidiasis
SAPs are important for the pathogenicity of C. albicans.
What is candidemia and why is it important clinically?
- Bloodstream infection by Candida
- 10–15% of nosocomial bloodstream infections
- Mortality ~30–50% even with treatment
Candidemia is a serious condition that poses a high risk of mortality.
Which two Cryptococcus species cause human disease and who do they mainly affect?
- C. neoformans – opportunistic, mainly immunocompromised (HIV, transplants)
- C. gattii – can infect immunocompetent hosts (e.g. Vancouver Island outbreak)
These species have different epidemiological profiles.
How is Cryptococcus acquired and what is the major disease it causes?
- Acquisition: Inhalation of environmental yeast/spores (soil, bird droppings, trees)
- Major disease: Cryptococcal meningitis (CNS dissemination from lungs)
Understanding the transmission route is crucial for prevention.
What are key virulence factors of Cryptococcus neoformans?
- Polysaccharide capsule (GXM)
- Melanin production
- Ability to survive/replicate inside macrophages
- Titan cell formation
These factors enhance the pathogenic potential of Cryptococcus neoformans.
Two main functions of the Cryptococcus capsule.
- Anti-phagocytic barrier; inhibits opsonisation and killing
- Modulates immune response (shed polysaccharide suppresses cytokines, leukocyte migration)
The capsule is a critical factor in evading the host immune system.
What are Titan cells and why are they important?
- Very large, polyploid Cryptococcus cells with thick capsule
- Too big to be phagocytosed; resist stress
- Produce normal-sized, stress-resistant progeny
Titan cells contribute to the survival and dissemination of Cryptococcus.
What is vomocytosis?
- Non-lytic expulsion of live Cryptococcus from macrophages
- Allows fungus to escape without killing the host cell, aiding dissemination (Trojan horse)
This mechanism facilitates the spread of the fungus within the host.
Which arms of adaptive immunity are most protective against fungi?
- Th1 (IFN-γ) → activates macrophages for systemic/intracellular fungi
- Th17 (IL-17, IL-22) → recruits neutrophils & reinforces mucosal barriers
These immune responses are crucial for controlling fungal infections.
Which T-helper defect is linked to chronic mucocutaneous candidiasis?
- IL-17 / Th17 pathway defects
Deficiencies in this pathway can lead to increased susceptibility to Candida infections.
What is Dectin-1 and what does it recognise?
- A C-type lectin receptor on myeloid cells
- Recognises β-1,3-glucan in fungal cell walls
- Signals via Syk–CARD9 → NF-κB, cytokines, phagocytosis
Dectin-1 plays a key role in the immune response to fungal infections.
Why are neutrophils so important in fungal infections?
- Kill fungi via phagocytosis, ROS, granule enzymes and NETs
- Crucial against hyphae (Candida, Aspergillus)
- Neutropenia = major risk for invasive fungal disease
Neutrophils are essential for controlling fungal infections.
Give three mechanisms neutrophils use to kill fungi.
- Phagocytosis + NADPH oxidase–derived ROS
- Degranulation (proteases, myeloperoxidase, defensins)
- NET formation (DNA + antimicrobial proteins)
These mechanisms are vital for the neutrophil’s antifungal activity.
What are the three main fungal PAMPs that distinguish fungi from mammalian cells?
- Chitin
- β-glucans
- Mannans (mannose-rich glycans)
These pathogen-associated molecular patterns are recognized by the immune system.
Why do we currently need fungal vaccines? (1–2 key reasons)
- Invasive fungal infections cause millions of deaths; rising in immunocompromised patients
- Limited, toxic antifungals + increasing resistance (e.g. Candida auris, azole-resistant Aspergillus)
- No licensed vaccines yet
The need for effective vaccines is critical due to the rising incidence of fungal infections.
