OPPORTUNISTIC MOLD INFECTIONS

Mold usually doesn’t infect people, but when they do it’s really really nasty. Today we’re gonna talk about Aspergillus .

Aspergillus is a genus with lots of species. They form long hyphae with cross walls dividing the hyphae into separate compartments. Most of them have asexual reproduction and make tons and tons of spores. The spores are produced by a specialized fruiting structure that looked to scientists like an aspergill (some sort of catholic thing) so they named the whole species aspergillus. Some species can undergo sexual reproduction.

Asexual Life Cycle

1. A spore is created (so small, it’s the size of the nucleus of a cell)

2. Flies away from it’s parents (these spores are so efficient they have been found in Antarctic ice and the Saharan desert)

3. Lands on a nice breeding ground

4. Swells and secretes sticky stuff so it can stay where it’s comfy

5. Makes a germ tube which starts to branch

6. The tip of the tube has enzymes needed for growth

7. After 24 hours makes mycellium

8. Aerial foot cells emerge and nuclei are pushed to the ends to form strings of conida

9. A regular petri dish can make 10^9 spores in 2 days.

Aspergillus can do good things –

• Coke uses it to make the citric acid that is a major ingredient.
  

• Actually, 99% of the citric acid added to food is made from Aspergillus.
  
• Enzymes from A. niger are used to degrade the mush that you have when you make apple juice, so we all can have pulp less Apple Juice.
  
• Soy sauce is fermented in the presence of A. oryzae.
  
• Lovastatin, a cholesterol-lowering drug, is made from A. terreus fermentation. Proteases and lipases from A. niger are used in detergents as stain removers.

But Aspergillus also does bad things. It secretes lots of poisons. In the 60’s a bunch of turkeys were dying in England. The cause was traced back to Columbian feed that had been contaminated by A. flavus, which produces Aflatoxin (a potent poison and carcinogen which causes liver cancer). Now all feed and grain is screened for it. It was used as a bioweapon by Iraq. Some people think that the curse of king Tut was caused by fungi.

Only 4 species of Aspergillus cause disease, and A. fumigatus causes 80% of the diseases. Here are the diseases ranging from the mildest to the most severe:

1. Allergic Bronchopulmonary Aspergillosis (ABPA)  an overreaction to spores, seen in 5% of asthmatics and 10-20% CF patients. It can cause permanent damage (fibrosis) to the lungs, and is treated by administration of corticosteroids.

2. Aspergilloma (fungus ball)  TB causes a cavity in the lungs and aspergillus gets in and forms a ball. Usually the patients are asymptomatic unless they become immunocompromised, then the fungus attack.

3. Invasive Aspergillosis (IA)  categorized according to where it attacks

   1. Aspergillosis Sinusitis  along with #2, very rare, seen in alcoholics AIDS patients, and diabetics who don’t take good care of themselves.

   2. Aspergillosis Tracheobronchitis

   3. Invasive Pulmonary Aspergillosis (IPA)  Spores are inhaled and then germinate and invade the tissue. They like to clog up blood vessels, causing necrotic death of the organ the blood vessel supplies. People who are immunosuppresed with neutropenia get it  leukemics, transplant patients, bone marrow transplant patients. It is actually rarely seen in AIDS. Patients get it because their alveolar macrophages don’t work very well, and neither do their neutrophils, which are there to swallow the spores when they get bigger. They have to rely on anti-fungals. There is 100% mortality when untreated and 60-90% when treated. It costs about $630 million/yr, mostly because the drugs are very expensive.

The drug of choice is amphoterecin B which binds to ergosterol and forms holes in the fungal membrane, which allow leakage and cell death. The only problem is that it also attacks human cells, especially the kidney. They tried to fix this by encasing it in a lipid and making lipid AMB. This has fewer side effects. They also use Itraconazole. The most effective thing they’ve found so far is Voriconazole and Caspofungin, which inhibits enzymes that make the cell wall. These two have fewer side effects. People are now talking about combination therapies to improve patients’ chances. Faster diagnosis would also improve patients’ chances.

Post-mortem diagnosis is usually a biopsy, but if you do this on a sick patient you’d probably kill him. You can culture sputum samples, but there is a problem with cross-contamination. You can also use a CT scan to see if there are whitish areas surrounded by a diffuse halo. There are also companies making kits using immunodiagnosis.

Category: Microbiology Notes