Lesson 3 - Modern Microbiology

What was the turning point for human mortality throughout history?

• Improved sanitation and hygiene: Reduced the spread of infectious diseases through cleaner water, waste management, and better hygiene.

• Discovery of antimicrobial drugs and vaccines: Helped prevent and treat infectious diseases, further reducing mortality.

What was the World War I & 1918 Flu Pandemic?

• January 1918-December 1920, two back-to-back influenza pandemics (a.k.a. “Spanish Flu”)

• WWI hastened the pandemic (crowded clinics, trenches, global population movement, malnourishment)

• Infected 500 million people worldwide, 50-100 million died (3-5% of the world’s population)

• Doctors relied on chemical antispetics

• The 1918 influenza pandemic highlighted the devastating consequences of infectious diseases before antibiotics were available.

What did Sir Alex Fleming Discover?

• 1928: Alexander Fleming discovered that Penicillium mould inhibited the growth of Staphylococcus bacteria, leading to the discovery of penicillin.

• 1940s: Mary Hunt discovered a more efficient penicillin-producing strain (Penicillium rubens) on a cantaloupe.

• 1941: Penicillin's effectiveness was demonstrated in a human patient.

• WWII: Pfizer began manufacturing penicillin for widespread use.

• 1950s: Synthetic antibiotics were being produced.

How was Penicillin tested and what did it cure?

• Florey and Chain (Oxford) purified penicillin and cured mice infected with staphylococci or streptococci

• Human trials proved successful, and penicillin saved countless lives in WWII

• Fleming, Florey and Chain received the 1945 Nobel Prize in Physiology and Medicine

What was the Golden Era of Antibiotic Discovery?

• A period approximately spanning the 1940s–1960s when many major antibiotic classes were discovered and introduced.

• Many antibiotics were discovered decades before their clinical introduction.

• The rate of discovery of new antibiotic classes subsequently declined.

Recap: Why do we care to Research Microbes?

What are the five major cellular targets of antibiotics, and what are examples of each?

• Cell wall synthesis: Inhibit peptidoglycan synthesis.

• Cell membrane integrity: Disrupt bacterial membranes.

• Protein synthesis: Inhibit translation.

• Nucleic acid function: Inhibit DNA or RNA synthesis.

• Intermediary metabolism: Inhibit folate synthesis.

What is the difference between antibiotics that target the 30S and 50S ribosomal subunits?

30S (small subunit): Responsible for decoding mRNA.

• Tetracyclines: Block tRNA binding.

• Aminoglycosides: Cause misreading of mRNA.

50S (large subunit): Responsible for peptide bond formation and protein elongation.

• Chloramphenicol: Inhibits peptide bond formation.

• Macrolides: Interfere with protein elongation.

Both inhibit bacterial protein synthesis (translation).

What is antimicrobial resistance (AMR), and why is it a growing concern?

• AMR occurs when microorganisms become resistant to antimicrobial drugs that previously inhibited or killed them.

• Increasing antibiotic use creates selective pressure favouring resistant bacteria.

• Resistance can emerge relatively soon after an antibiotic is introduced.

• This reduces antibiotic effectiveness and contributes to a growing global health crisis.

What are the major global health and economic impacts of antimicrobial resistance (AMR)?

• Over 5 million deaths worldwide were associated with bacterial AMR in 2019.

• AMR costs Canada approximately $2 billion annually in medical care.

• E. coli and S. aureus were the leading pathogens associated with resistance in 2019.

• AMR is a worldwide crisis with substantial projected future mortality.

• One Health recognizes that human, animal, plant, and environmental health are interconnected.

• AMR affects humans, animals, and the environment, making it a global health concern.

Why do infectious diseases remain a concern despite advances in sanitation, vaccines, and antibiotics?

1. Emergence and re-emergence of infectious diseases: New diseases emerge and previously controlled diseases return (e.g., HIV/AIDS, Ebola, SARS-CoV-2).

2. Changing susceptibility to infections:

   • Compromised immune systems (e.g., HIV/AIDS, chemotherapy, immunosuppressants, organ transplants, aging).

   • Microbiome disruption (e.g., prolonged antibiotic treatment, stress, malnourishment).

Examples: Fungal infections and Clostridioides difficile.

How do population density, globalization and climate change/global warming contribute to the spread of infectious diseases?

• Population density: More people living in close proximity increases opportunities for disease transmission.

• Globalization: Increased international travel and population movement facilitate the spread of infectious diseases across countries and continents.

• Climate change alters environmental conditions, potentially affecting the geographic distribution and transmission of infectious diseases.

• Changing temperatures can influence where disease-carrying organisms can survive.

• As a result, infectious disease risks may change across different regions.

How has the focus of microbiology research evolved over time?

• Historically (over 150 years), microbiology primarily focused on microorganisms causing human infectious diseases.

• Technological advancements (e.g., microscopy, bacterial culturing, genetics, molecular biology) expanded microbial research.

• Scientists recognized that most microorganisms do not cause disease and are essential to life in the biosphere.

• This led to new specialties, including environmental microbiology, microbial ecology, microbiome research, and industrial microbiology.

What is known about the relationship between the human microbiome and health?

• Gut microbiome composition and function have been linked to metabolic disorders, mental health disorders, cancers, and neurodegenerative diseases.

• Antibiotic use can disrupt the microbiome.

• The microbiome contains enormous microbial diversity, much of which remains poorly characterized and understood.

Important: Associations between the microbiome and disease do not necessarily establish causation.

What role do microorganisms play in food production and fermentation?

• Microorganisms are used in fermentation to produce various foods and beverages.

• Microbial metabolism produces compounds that contribute to food flavour, aroma, and texture.

• Examples include yogurt, cheese, and bread.

• This demonstrates the beneficial applications of microorganisms beyond causing disease.