Chapter 20

Control of Microbial Growth

  • Infectious Diseases:

    • Definition: Microbes have invaded or colonized an individual's body, leading to a change in health.

    • Infectious diseases involve damage caused by the colonization of microbes.

Treatment of Infectious Diseases

  • Selectively Toxic Treatments:

    • Goal: Develop treatments that do not affect host eukaryotic cells but target prokaryotic (bacterial) cells specifically.

    • Importance: Understanding structural differences between eukaryotic and prokaryotic cells.

Antimicrobial Drugs

  • Types of Antimicrobials:

    • Focus on antibiotics, which specifically target bacteria.

    • Antibiotic discovery: Penicillin (1928) by Alexander Fleming; derived from fungus which inhibited bacterial growth.

    • Widespread use of penicillin began around 1945, but resistance has led to decreased prescription.

  • Sources of Antibiotics:

    • Most antibiotics are produced by microorganisms such as fungi and bacteria (e.g., bacitracin, neomycin, penicillin).

    • Production of antibiotics provides a competitive advantage in nutrient-limited environments.

Spectrum of Activity

  • Narrow vs. Broad Spectrum:

    • Narrow Spectrum Antibiotics:

      • Target specific types of bacteria only (e.g., Penicillin targets gram-positive bacteria).

    • Broad Spectrum Antibiotics:

      • Affect multiple types of bacteria (e.g., Streptomycin affects mycobacteria and gram-negative bacteria).

      • Tetracycline is very broad, targeting both gram-positive and gram-negative bacteria, as well as chlamydia.

Kirby-Bauer Assay

  • Purpose: Test the effectiveness of antibiotics.

  • Procedure:

    • Inoculate bacteria onto a plate and place antibiotic discs on it.

    • Incubation allows antibiotics to diffuse, resulting in a zone of inhibition if effective.

    • Antibiotics can be bactericidal (kill bacteria) or bacteriostatic (prevent replication).

Modes of Action of Antibiotics

  • Five Key Mechanisms:

    1. Inhibiting Cell Wall Synthesis:

      • Examples: Penicillins and cephalosporins weaken the cell wall, leading to lysis due to osmotic pressure.

    2. Inhibiting Protein Synthesis:

      • Target 70S ribosomes in bacteria, preventing translation (e.g., streptomycin, tetracyclines).

    3. Inhibiting Nucleic Acid Replication:

      • Quinolones and Rifampin inhibit DNA replication and transcription respectively.

    4. Damaging Plasma Membrane:

      • Polymyxin B interacts with the bacterial membrane, causing cell death.

    5. Inhibiting Metabolic Enzyme Activity:

      • Sulfonamides act as competitive inhibitors for folic acid synthesis, leading to bacterial death.

Antibiotic Resistance

  • Definition: Mechanisms by which bacteria avoid being affected by antibiotics.

  • Five Mechanisms of Resistance:

    1. Preventing Entry: Decreased uptake of antibiotics through altered transport proteins.

    2. Efflux Pumps: Actively pump antibiotics out of the cell.

    3. Inactivating Enzymes: Break down antibiotics inside or outside the cell.

    4. Alternative Pathways: Bacteria can bypass inhibited enzymes with alternative metabolic pathways.

    5. Altered Target Proteins: Modify target proteins so that antibiotics do not bind effectively.

Genetic Changes in Bacteria

  • Mutation: Leads to proteins that may alter antibiotic targets, making bacteria resistant.

  • Transformation: Uptake of naked DNA from the environment can confer resistance genes.

  • Transduction: Bacterial genes transferred by phages can introduce resistance properties.

  • Conjugation: Transfer of plasmids containing resistance genes between bacteria, often through pilus formation.

Natural Selection

  • Mechanism: Explains how antibiotic resistance develops in bacterial populations.

  • Example: Initial antibiotic treatment may kill sensitive bacteria, allowing resistant strains to survive and proliferate.

Other Antimicrobials

  • Antiviral Drugs: Limited options due to similarities between host and virus replication machinery.

    • Example: Acyclovir targets thymidine kinase in herpes-infected cells.

  • Antifungal Drugs: Target chitin in fungal cell walls or ergosterol in cell membranes, selectively toxic due to differences from human cells.

  • Antiprotozoal Drugs: Difficult to achieve selectivity due to similarity to human cells, necessitating careful dosing.

  • Antihelminthic Drugs: Affect energy production or paralyze helminths; overdosing can lead to human toxicity.

Conclusion

  • Distinct mechanisms, actions, and resistance present unique challenges and opportunities in the development and application of antimicrobials to effectively combat infections.