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Cellular Remodelling and Antifungal Drug Resistance
Context:
- A new study led by Michigan State University researchers reveals how fungi adapt to evade antifungal treatments.
- Aspergillus fumigatus, a major cause of invasive fungal infections in immunocompromised individuals, causes around 100,000 deaths annually.
Key Findings of the Study & Implications:
- Antifungal Drug Mechanism: Antifungal drugs, such as echinocandins, target molecules in the fungal cell wall, a protective yet rigid layer. These drugs aim to rupture the cell wall to kill the fungal cell and control infection.
- Fungal Adaptation: Fungi have evolved mechanisms to rebuild and reinforce their cell walls in response to drug attacks. This adaptation involves modifying cell wall architecture to enhance survival.
- Structural Changes: Upon echinocandin exposure, fungi decrease b-glucans and increase other related molecules, reshuffling polysaccharide structures (e.g., galactomannan, galactosaminogalactan) to strengthen the cell wall and enhance its hydrophobic properties. The new cell wall architecture often eliminates drug targets, reducing the effectiveness of treatments and allowing the fungi to persist.
- Clinical Implications: Fungal spores, while ubiquitous, can overwhelm individuals with compromised immune systems (e.g., cancer patients, organ transplant recipients, those with AIDS or COVID).
- Infection Challenges: Once established in the lungs, fungal infections are difficult to eliminate even with drugs or surgery.
- Current Drug Limitations: Only four families of antifungal drugs are available, each facing limitations due to fungal resistance mechanisms. Understanding these mechanisms is crucial for developing more effective treatments.
 
Aspergillus Fumigatus Overview:
Risk Factors for Infection:
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Difference Between Viruses, Bacteria, and Fungi:
1) Viruses:
Structure:
- Smaller than bacteria and fungi.
- Genetic material (DNA or RNA) enclosed in a protein coat and sometimes a lipid envelope.
- They lack cellular structures.
Reproduction:
- Cannot reproduce on their own.
- They must invade a host cell and hijack the cell’s machinery to replicate and produce new virus particles.
Living Status:
- Considered as non living organisms, cannot carry out life processes independently.
Diseases:
- Examples include influenza (flu), HIV, and COVID-19.
2) Bacteria:
Structure:
- Single-celled organisms with a simple cell structure.
- They have a cell wall, cell membrane, cytoplasm, and genetic material (DNA) not enclosed in a nucleus.
Reproduction:
- Reproduce asexually through binary fission, where a single bacterial cell divides into two identical cells.
- Living Status:
- They are living organisms capable of carrying out all necessary life processes on their own.
Diseases:
- Ex- tuberculosis, whooping cough, and bacterial infections such as strep throat.
3) Fungi:
Structure:
- Can be single-celled (like yeasts) or multicellular (like moulds and mushrooms).
- Have a complex cell structure with a defined nucleus and cell wall made of chitin.
Reproduction:
- Both sexually and asexually through spores.
- Can grow and spread by producing spores that can disperse through the air, water, or other means.
Living Status:
- Living organisms, distinct from bacteria and viruses in their cellular complexity.
- Diseases: Ex- ringworm, athlete’s foot, and aspergillosis.
Infection Control:
Viruses:
- Typically require antiviral medications or vaccines for prevention and treatment.
- Hygiene practices and vaccines are crucial for control.
Bacteria:
- Often treated with antibiotics, though resistance is a growing problem.
- Good hygiene and appropriate use of antibiotics are essential.
Fungi:
- Treated with antifungal medications.
- Preventive measures include proper hygiene and environmental control.
