Medical Mycology & Biotechnology – Lecture Summary Flashcards

These flashcards cover the main concepts, definitions, clinical issues, and biotechnology strategies presented in the Medical Mycology & Biotechnology lecture, enabling effective revision for exams.

What are the three steps in medical biotechnology outlined by Dr Lenardon?

1) Understand the disease 2) Assess the clinical needs 3) Exploit biological knowledge to meet those needs.

Give the Australian-government definition of medical biotechnology.

The use of living cells and cell materials to research and produce pharmaceutical and diagnostic products that help treat and prevent human diseases.

Define mycology.

The study of fungi (from the Greek ‘mykes’ meaning fungus and ‘-logy’ meaning study).

Provide a concise biological definition of a fungus.

A chemo-organotrophic eukaryote that lacks chlorophyll, forms spores, has a chitin- or cellulose-containing cell wall, contains ergosterol in its membrane, and absorbs nutrients.

Which sterol stabilises fungal cell membranes and how does it differ from humans?

Ergosterol; human cell membranes use cholesterol instead.

Name the three traditional morphological types of fungi.

Mushrooms, moulds and yeasts.

List two beneficial ecological roles of fungi mentioned in the lecture.

Recycling nutrients in soil and degrading plastics.

Into which two broad categories are human fungal infections divided?

Superficial (surface) infections and invasive/systemic infections.

Give three common examples of superficial fungal infections.

Ringworm (tinea), athlete’s foot, and fungal nail infections.

Approximately what proportion of the world’s population is affected by superficial fungal infections?

At least 25 % of the global population.

Name the five collective groups that account for most invasive human mycoses (WHO list).

Infections caused by Candida spp., Aspergillus spp., Cryptococcus spp., the Mucorales (mucormycosis), and Pneumocystis jirovecii.

What is the untreated vs treated mortality range for invasive fungal infections?

Untreated ≈ 90 % mortality; treated still ≈ 35–60 % mortality.

Which invasive fungal pathogen is Dr Lenardon’s main research focus?

Candida albicans.

List three distinct morphologies that Candida albicans can adopt.

Yeast, pseudohyphae, and true hyphae.

Where is C. albicans normally found in healthy humans and how is it controlled?

It colonises the gastrointestinal tract and is kept in check by bacterial microbiota competition and innate immune phagocytes (neutrophils, macrophages).

Name four patient groups at high risk for systemic candidiasis.

Cancer patients, organ/stem-cell transplant recipients, immunosuppressed individuals (e.g. AIDS), and ICU patients undergoing major surgery.

Why is rapid diagnosis critical for candidemia outcomes?

Because patients can progress to sepsis and death within the 72 h it usually takes to obtain culture results.

What is the current ‘gold standard’ for diagnosing invasive candidiasis and its sensitivity?

Blood culture; only ~50 % sensitive (misses half of true positives).

State two major limitations of PCR-based fungal diagnostics.

1) Difficult lysis/DNA extraction from tough fungal cell walls; 2) DNA detection cannot easily distinguish harmless colonisation from invasive disease.

Differentiate between an antibiotic and an antifungal drug.

Antibiotic: inhibits or kills bacteria; Antifungal: inhibits or kills fungi.

Why are there far fewer antifungal drug classes than antibiotic classes?

Because fungi and humans are both eukaryotes and share many cellular features, giving fewer unique targets.

Name the three antifungal classes routinely used for systemic candidiasis and one example of each.

Polyenes (Amphotericin B), Azoles (Fluconazole), Echinocandins (Caspofungin).

What is the main toxicity issue with polyenes such as Amphotericin B?

They can bind cholesterol as well as ergosterol, causing human cell toxicity.

What major clinical problem is reducing the efficacy of azole antifungals?

Widespread antifungal resistance mechanisms in fungi.

Which cell-wall sugar synthesis is blocked by echinocandins?

β-1,3-glucan synthesis.

Identify the three main structural components of the C. albicans cell wall.

Chitin fibrils, β-1,3-glucan helices, and mannosylated cell-wall proteins.

What layer forms the outermost ‘fibrils’ seen on electron micrographs of the C. albicans wall?

Mannan chains on mannosylated cell-wall proteins.

Define an antibody epitope.

The specific part of an antigen to which an antibody binds.

What determines the antigen specificity of an antibody molecule?

The DNA sequence of the complementarity-determining regions (CDRs) in its variable domains.

Compare polyclonal and monoclonal antibody preparations.

Polyclonal: mixture of antibodies recognizing multiple epitopes on an antigen; Monoclonal: identical antibodies from one B-cell clone, binding a single epitope.

State two advantages of monoclonal antibodies as therapeutics/diagnostics for fungi.

High specificity (reduced off-target toxicity) and ability to exploit even subtle fungal-human differences.

Why are antibody fragments (e.g., scFv) useful in early research stages?

They are smaller, easier, and cheaper to express in E. coli for screening binding and function.

Name the technology Dr Lenardon’s team used to isolate anti-mannan antibody sequences.

Phage display.

Which two scFv clones were identified that bind Candida albicans mannan?

Clones 1A2 and 1H6.

How specific were scFv 1A2 and 1H6 for Candida albicans mannan?

They bound C. albicans mannan exclusively, with no binding to other fungal or non-fungal sugars tested.

Describe one in-vitro and one in-vivo result supporting the therapeutic potential of these scFvs.

In-vitro: 1A2 & 1H6 killed C. albicans and related species; In-vivo: 1H6 prolonged survival of infected Galleria mellonella larvae.

Give one caveat of using small antibody fragments directly in humans.

Their small size leads to rapid clearance (renal/hepatic) and they may elicit immune responses if produced in bacteria, so humanised/full-length formats are preferred clinically.

Summarise the key unmet clinical needs in systemic candidiasis identified in the lecture.

Faster, more sensitive diagnostics and new, less toxic, resistance-proof antifungal therapies.

Explain how the monoclonal-antibody project embodies the three steps of medical biotechnology.

1) Disease understood: C. albicans cell-wall mannan unique; 2) Clinical need: better diagnosis/therapy; 3) Exploitation: engineered monoclonal antibodies targeting mannan for diagnostics and treatment.

Which WHO priority level includes Candida albicans and Candida auris?

Critical priority group.

Why is cell-wall targeting considered conceptually safer for antifungal therapy?

Human cells lack cell walls, so drugs/antibodies against wall components spare human tissues.