Human fungal infections 2

• Describe the candida species

  This is an opportunistic yeast found in the gut, oral and genitourinary tracts. This can cause mucosal candidiasis, which often occurs following in resident microflora or defects in cell-mediated immunity. Or it can cause disseminated candidiasis, which usually originates in the gastrointestinal tract as a result of a physical breach or impaired innate immunity. Furthermore, usually disseminates into the kidney to form hyphae.
• Describe some of the virulence factors of fungi

  1. Expression of invasins: allows the fungi to invade host cell
  2. Fungal hydrolases: toxic to host cells
  3. Biofilm formation: composed of different morphotypes of fungi cells to form a complex structure, which is resistant to the action of anti-fungals.
  4. Opaque form: resistant to low pH so allows them to grow in the stomach
• Describe how C. albicans can transition from yeast to hyphae


  Yeast cells produce filamentous hyphae in order to promote tissue invasion, tissue penetration and colonisation. These hyphae can penetrate between and through cells and then disseminate into the vascular system. Transitioning also allows them to mask their PAMPs from immune cells. Finally, nutrient starvation stimulates the fungi to switch from yeast to filamentous hyphae morphology, which physically breaks through the macrophage and, in some cases, allows it to escape.
• What is candidalysin?


  This is a fungal cytolytic peptide toxin that directly damages epithelial membranes, triggers a danger response signalling pathway and activates epithelial immunity. This occurs as the toxin activates epidermal GF receptor in epithelial cells and the NLRP2 inflammasome in macrophages, as well as driving neutrophil recruitment. Then forms pores in host membranes, causing cell damage.
• Describe the Aspergillus species


  This is a species of filamentous fungi and a major component of the airborne microflora. It is the most potent infectious mould as it sporulates abundantly and it the most cultured fungi from the airways of chronically ill humans. Infection can cause chronic lung disease, asthma and cystic fibrosis.
• Describe some of the virulence factors of Aspergillus. fumigatus

  1. Small, thermotolerant and hydrophobic spores
  2. Adaption to stress and nutrients/trace elements limitation
  3. Production of potent secondary metabolites
  4. Secretion of proteases
  5. Production of catalases (neutralises low pH), superoxide dismutases (breaks down harmful oxygen molecules) and glutathione transferases (detoxify ROS)
• Describe how Aspergillus fumigatus' conidia increase virulence

  • Melanin shedding during germination activates autophagy and promotes fungal killing
  • Melanin inhibition of LC3-associated phagocytosis promotes virulence of aspergillus fumigatus
• What is gliotoxin?


  This is a member of the epipolythiodioxopiperazine class of toxins and it the most potent toxin produced by aspergillus fumigatus. Activates Bak to mediate cell apoptosis.
• Describe the cryptococcus species

  This is a species of encapsulated yeast and is the most common lethal fungal infection in patients with AIDs worldwide. The reservoirs exist in nature and cause infection via inhalation.
• Describe the virulence factors of Cryptococcus neoformans

  1. Thermotolerance- can survive at high temperatures
  2. Capsule- antiphagocytic, inhibits leukocyte migration and dysregulates cytokine secretion
  3. Intracellular lifestyle
  4. Antigen masking- mRNA decay-dependent reprogramming
• How does Cryptococcus neoforms live intracellularly?


  Alveolar macrophages play paradoxical roles in defence against Cryptococcus infections by clearing fungal cells. However, C. neoforms can survive and divide inside macrophages' phagolysosomes and escape. This creates a latency period where the fungi are internalised and growing and dividing.
• What are the different non-protein toxins?

  • Endotoxins: embedded in the cell surface and specific to LPS. They do not get released but remain on the bacterial surface.
  • Other bacterial cell wall components: Lipoteichoic acid
  • Mycolactone: polyketide-derived macrolide produced by some mycobacteria. This toxin is responsible for Buruli ulcer
• What are protein toxins?

  These toxins are excreted from the cell and can be characterised into three classes:

  • Type I - superantigens
  • Type II - phospholipases and pore-forming toxins
  • Type III - A-B toxins
• Compare endotoxins and exotoxins

  Endotoxin

  • LPS specific
  • Part of the outer membrane
  • Relatively low potency

  Exotoxin

  • Protein
  • Extracellular and diffusible
  • Relatively high potency
• What are the 5 cardinal signs of inflammation?

  1. Heat- increased blood flow
  2. Redness: vasodilation
  3. Swelling: increased vascular permeability
  4. Pain: inflammation
  5. Loss of function: chronic inflammation