Fungal Biology - Control of Fungal Growth

Control of Fungal Growth

Environmental and Biological Factors

• Fungi can be managed by controlling physical and environmental conditions.
• Controlled atmosphere storage is used for fresh produce, combining cool temperatures and elevated carbon dioxide levels.
• Sanitation, quarantine, and biologically based strategies are important.
• Crop rotation is an effective method for controlling plant diseases.
• Adjusting crop management practices can help avoid diseases.
• Meteorological forecasting aids in disease management.
• Sanitation helps control or avoid disease.
• Quarantine prevents the spread of pathogens.

Biological and Integrated Control

• Biological control involves using other organisms to control undesirable ones.

Cellular Targets of Antifungal Agents

• Main cellular targets for chemical control:
  1. Cell membrane: Targeting ergosterol, a unique fungal membrane sterol.
  2. Microtubules and microfilament-associated proteins: Disrupted by griseofulvin and benzimidazole fungicides.
  3. Mitochondrial respiration: Targeted by some plant fungicides.
  4. Fungal cell wall components: Especially β1-3 glucans, targeted by echinocandins.
  5. General metabolism.

Fungicides for Plant Disease Control

• Fungicides broadly kill or inactivate fungi.
• Most are chemically synthesized, some are modified natural compounds.
• Categories of fungicides:
  • Inorganic fungicides: Sulphur, Copper or Mercury based. Limited use due to insolubility, but effective as dust on leaves to control powdery mildew fungi.
  • Organic contact (protectant) fungicides: Act only at the application site to protect plant surfaces or control established infections. Examples include dithiocarbamates like maneb and thiram.
  • Systemic fungicides: Absorbed by plants and distributed internally, usually in the xylem, protecting new growth.

Systemic Fungicides

• Benzimidazole compounds: First systemic fungicides introduced (thiabendazole, benomyl, carbendazim, thiophanate-methyl).
• Ridomil: Used to control systemic diseases like downy mildews.

Control of Fungal Infections in Humans

• Presents difficulties due to compromised or immunosuppressed patients.

Griseofulvin

• Naturally occurring antifungal antibiotic from Penicillium griseofulvum.
• Used for dermatophyte infections of keratinized tissues.
• Fungistatic, requiring prolonged treatment until infected tissues are shed.
• Treats dermatophytoses (ringworm) such as fungal infections of nails, scalp, and skin (Tinea spp).

Antifungal Antibiotics

• Table 17.3 lists some antifungal antibiotics used for control of plant or human mycoses.

Terbinafine

• An antifungal medication that fights infections caused by fungus
• Taken orally or topically, accumulates in skin, nails, hair, and fatty tissues.
• Oral granules treat scalp hair follicle infections in children (4+ years).

Polyene Macrolide Antibiotics

• Produced by several Streptomyces spp.
• Structure exemplified by amphotericin B.
• Amphotericin B, nystatin, and pimaricin (natamycin) are used in veterinary medicine.

Azole Drugs

• Ergosterol biosynthesis inhibitors similar to those for plant disease control.
• Designed for treating systemic mycoses of humans.
• Inhibit fungal wall synthesis by inhibiting ergosterol synthesis.
• Ergosterol is key component of fungal cell membranes.

Candidiasis Treatment

• Fluconazole: Prevents and treats fungal and yeast infections.
• Azole antifungal.
• Stops the growth of fungus, e.g., Vaginitis.
• Thrush in males: affects the head of the penis and the foreskin, leading to inflammation (balanitis).
• Symptoms: thick, white, lumpy discharge, unpleasant odor, difficulty pulling back foreskin.
• Oral thrush: affects mucous membranes of the mouth.
• CDC-recommended drugs: Clotrimazole (Lotrimin), Econazole nitrate (Specazole), Miconazole nitrate (Monistat).

Azole and Triazole Agents

• Triazole agents: fluconazole, itraconazole, econazole, terconazole, butoconazole, tioconazole.
• Newer triazoles (voriconazole, posaconazole, ravuconazole) are effective against fluconazole-resistant Candida strains.
• Treat and prevent mycosis, athlete's foot, ringworm, candidiasis (thrush), systemic infections (cryptococcal meningitis).
• Ketoconazole: First developed for human treatment. Effective against Candida and Cryptococcus neoformans, and other systemic pathogens, but less effective on Aspergillus.
• Ketoconazole topical: Treats athlete's foot, jock itch, ringworm, and seborrhea.

Other Antifungal Agents

5-Flucytosine (5-FC)

• Fluorine-substituted nucleoside, originally an antitumour agent with antimycotic effects.
• Treats systemic Candida and Cryptococcus infections.
• Used with amphotericin B for serious infections.

Echinocandins

• Inhibit the synthesis of β1-3 glucan.
• Caspofungin: Licensed for clinical use in 2002.
• Anidulafungin and mycafungin: Other compounds in this structural class.
• Caspofungin: Treats fungal infections in the stomach, lungs, esophagus, or other internal areas.

Micafungin

• Treats infections caused by Candida fungus.

Anidulafungin

• Treats fungal infections including candidemia, candida peritonitis and abscess, esophageal candidiasis, and other fungal infections.

The Future

• Despite advances in controlling fungal infections, development of drugs with novel modes of action is slow.
• New inhibitors are needed for effective antifungal therapy due to the emergence of resistance (Odds et al., 2003).
• Increased interest in vaccines to protect against endemic human-pathogenic fungi.
• Potential antigens identified for Coccidioides immitis/posadasii (Magee & Cox 2004) and Paracoccidioides brasiliensis (Travassos et al. 2004).