Hybrid Seminar Notes: Understanding Microbial Life and Antibiotic Resistance

Introduction

• Welcome to the seminar on the Cambridge Biomedical Campus Tours.
• Technical details: Q&A at the end, online audience to submit questions.

Overview of LNB (MRC Laboratory of Molecular Biology)

• Located on Addenbrooke's campus.
• Focus on understanding biological processes at atomic, molecular, cellular, and organism levels.
• Aims to address long-term biological problems impacting human health.

Speaker Introduction: Tanmay Bharat

• Background:
  • BSc in Chemistry (University of Delhi, India)
  • BA in Biological Sciences (University of Oxford)
  • PhD from the European Molecular Biology Laboratory, Heidelberg (2012)
  • Postdoctoral training at LMBE with Jan Loewe
  • Group leader at University of Oxford, then returned to LMB as a program leader (2022)
• Research focus: Understanding how bacteria evade antibiotic treatment and developing new treatment strategies.

Microbial Life

Overview of Microorganisms

• Microorganisms include bacteria and archaea; humans are eukaryotes.
• Bacterial cells lack compartmentalization, are simpler than eukaryotic cells.
• Size comparison:
  • Human cells: ~100 microns
  • Prokaryotic cells: 1-10 microns
• Microorganisms were the first life forms on Earth (5 billion years ago).

Distribution of Microorganisms

• Estimated 1 trillion microbial species on Earth.
• Microorganisms outnumber all plants and animals combined in terms of weight.
• Found in various extreme environments:
  • Hot springs (Yellowstone)
  • Cold conditions (Antarctica)
  • Hyper-saline environments (Dead Sea)
  • Nuclear contaminated sites (Chernobyl)

Microbiome and Human Health

• Humans host over 100 trillion microbes, beneficial for digestion and protection.
• Imbalance can lead to diseases caused by bacteria such as:
  • Neisseria meningitis (meningitis)
  • Staph aureus (skin infections)
  • E. coli (urinary tract infections)

Antibiotic Treatments and Resistance

Discovery of Antibiotics

• Penicillin discovered by Alexander Fleming; revolutionized treatment of bacterial infections.
• Antibiotics target bacterial ribosomes without harming human cells.
• Impact of antibiotics in history (e.g., during WWII).

Antibiotic Resistance

• Bacteria develop resistance mechanisms, making treatment difficult.
• Examples of resistant bacteria include:
  • Pseudomonas aeruginosa
  • Staph aureus
  • Shigella
• Biofilm formation as a primary resistance mechanism:
  • Bacteria adhere to surfaces, forming protective extracellular matrices.
  • Over 75% of human infections involve biofilms.

Laboratory Research: Pseudomonas aeruginosa

Biofilm Structure and Function

• Biofilms allow bacteria to survive antibiotic treatments.
• Studying the organizational principles of biofilms in the lab to inform treatment approaches.

Research Findings

• Identified a master adhesive protein that facilitates biofilm formation.
• Created antibodies (nanobodies) that can penetrate biofilms and kill bacteria.
• Investigating protective mechanisms of biofilm bacteria, including:
  • PF4 protein forming liquid crystalline droplets that shield bacteria from antibiotics.

Potential Treatments

• Utilization of bacteriophages as an alternative therapy.
• Development of new antibiotics derived from natural sources:
  • Darobactin and tyxobactin as promising new compounds.

Conclusion

• Emphasis on collaboration between fundamental research and clinical application to combat antibiotic resistance.
• Acknowledgment of past scientists’ contributions and current research efforts.
• Closing remarks encouraged further inquiry into the microbiome and antibiotic resistance.