Ch. 10: Controlling Microbial Growth in the Body

Overview of Microbial Growth Control in the Body

• Key Concept: Managing microbial growth is crucial for human health.
  • Drugs are utilized to target pathogens without harming the host.
• Selective Toxicity: Essential for antimicrobial action, meaning the drug must kill the pathogen but not harm human cells.

Antimicrobial Agents

• Definition: Chemicals affecting physiological functions, specifically targeting diseases.
• Chemotherapeutic agents: Antimicrobials designed to treat infections.
• Common Sources: Most antibiotics derive from secondary metabolites produced by fungi and bacteria.

Historical Context

• Early 1900s: Approximately one-third of children did not survive past age five due to infectious diseases.
  • Innovations in Treatment:
  • Salvarsan (1910): First modern chemotherapeutic agent for syphilis.
  • Penicillin (1929): Discovered by Alexander Fleming, widely available by late 1940s.
  • Sulfanilamide (1932): First practical antimicrobial inhibiting nucleic acid synthesis.

Key Factors for Antimicrobial Action

• Diversity of Antimicrobials: Largest number available for antibacterial drugs.
  • Antiviral drugs are significantly less common and less effective.

Mechanisms of Antimicrobial Action

• Target Areas:
  • Inhibit bacterial cell wall synthesis, protein synthesis, cytoplasmic membranes, metabolic pathways, and nucleic acid replication.

Inhibition of Cell Wall Synthesis

• Beta-lactams: Common agents prevent cross-linking of NAM subunits in cell walls, causing bacteria to weaken and lyse.
• Selectivity: Effective only against growing cells.
  • No effect on human cells due to the absence of peptidoglycan.

Inhibition of Protein Synthesis

• Ribosomal Targeting: 70S ribosomes in prokaryotes vs. 80S in eukaryotes:
  • Targeting can lead to selective inhibition of bacterial translation without affecting human cells significantly.
  • Examples: Aminoglycosides (e.g., streptomycin), tetracyclines, chloramphenicol.

Disruption of Cytoplasmic Membranes

• Amphotericin B: Targets ergosterol in fungal membranes, poses some risk to human cells with cholesterol.

Inhibition of Metabolic Pathways

• Mechanisms:
  • Heavy metals inactivate enzymes.
  • Drugs can block viral activation and hinder nucleic acid biosynthesis.
  • Example: Sulfa drugs inhibit DNA and RNA nucleotide synthesis.

Nucleic Acid Analogs

• Structurally similar to nucleotides but lacking critical atoms, which terminate nucleic acid synthesis:
  • Examples: Acyclovir, Remdesivir, Retrovir, which interfere with viral replication.

Inhibition of Attachment

• Viral Replication: Neuraminidase's role in virus release; inhibitors like Relenza and Tamiflu prevent new virions from leaving the host cell.

Efficacy of Antimicrobial Agents

• Testing Methods:
  • Disk-Diffusion Test (Kirby-Bauer): Measures antibiotic effectiveness against microorganisms.
  • Minimum Inhibitory Concentration (MIC): Lowest concentration preventing growth.
  • Minimum Bactericidal Concentration (MBC): Lowest concentration that kills bacteria.

Administration Considerations

• Site of Infection: Antimicrobial agents must reach the target area effectively.
  • Administration routes vary (topical, oral, IM, IV).

Safety and Side Effects

• Adverse Effects: Potentially toxic to kidneys, liver, and nerves, may cause irreversible effects like teeth and bone damage.
• Allergic Reactions: Rare, yet can be severe.
• Disruption of Normal Flora: May lead to yeast infections or pseudomembranous colitis.

Development of Resistant Organisms

• Mechanisms of Resistance:
  • Mutation, plasmid acquisition, enzyme production (e.g., beta-lactamase).
  • Drug resistance becomes a major issue when the majority of the microbial population is resistant.

Strategies to Combat Resistance

• Approaches:
  • Maintain high drug concentrations, use combination therapies, develop novel drug variations, limit antimicrobial use to necessary cases.
• Innovative Solutions: Exploring potential crossover with anti-cancer treatments.