Controlling Microbial Growth in the Body: Antimicrobial Drugs (Lecture 9, Part I)

Controlling Microbial Growth in the Body

Introduction

This study guide covers the principles and mechanisms by which antimicrobial drugs control microbial growth within the human body. It includes definitions, the concept of selective toxicity, mechanisms of drug action, and the distinction between narrow and broad-spectrum drugs.

Key Terms and Definitions

Drugs, Chemotherapeutic Drugs, and Antimicrobial Drugs

• Drugs: Substances that affect physiology in any manner. Examples include caffeine, alcohol, tobacco, and antibiotics.

• Chemotherapeutic drugs: Agents that act against diseases. Examples: insulin, anticancer drugs, antibiotics.

• Antimicrobial drugs: Drugs used specifically to treat infections, such as antibiotics.

Example: Penicillin is both a chemotherapeutic and antimicrobial drug, as it treats bacterial infections.

Selective Toxicity of Antimicrobial Drugs

Principle and Implications

Selective toxicity is the ability of a drug to target pathogens with minimal harm to the host. The greater the differences between pathogen and host, the more potential drug targets exist.

• Selective toxicity: Drug must be more toxic to the pathogen than to the host.

• Implications:

  • Many antibacterial drugs exist because bacteria are very different from humans.

  • Fewer antifungal and antiprotozoal drugs are available due to similarities between these eukaryotes and human cells.

  • Very few antiviral drugs exist because viruses use host cell machinery for replication.

Example: Amphotericin B targets ergosterol in fungal membranes, a molecule not found in human cells.

Mechanisms of Action of Antimicrobial Drugs

Overview

Antimicrobial drugs act by interfering with essential processes in pathogens. The main mechanisms are:

• Inhibition of cell wall synthesis

• Inhibition of protein synthesis

• Disruption of cytoplasmic membranes

• Inhibition of metabolic pathways

• Inhibition of nucleic acid synthesis

• Inhibition of attachment/entry

Inhibition of Bacterial Cell Wall Synthesis

Drugs such as beta-lactams (e.g., penicillins, cephalosporins) prevent the formation of peptidoglycan cross-links, weakening the cell wall and causing lysis.

• Beta-lactams: Contain a critical β-lactam ring.

• Mechanism: Bind enzymes that form cross-bridges between N-acetylmuramic acid (NAM) subunits.

Example: Penicillin and Cephalosporin are beta-lactam antibiotics.

Equation:

$\text{Peptidoglycan cross-linking:} \quad \text{NAM} - \text{Enzyme} - \text{NAM} \rightarrow \text{Cell wall integrity}$

Inhibition of Protein Synthesis

Antibiotics target ribosomes, which differ between prokaryotes and eukaryotes.

• Prokaryotic ribosomes: 70S (30S + 50S subunits)

• Eukaryotic ribosomes: 80S (40S + 60S subunits)

• Examples:

  • Streptomycin binds 30S subunit

  • Tetracycline blocks tRNA binding

  • Erythromycin binds 50S subunit

Additional info: These drugs exploit structural differences to avoid harming human cells.

Disruption of Cytoplasmic Membranes

Some drugs target membrane components unique to pathogens.

• Azoles: Antifungals that inhibit ergosterol synthesis (fungal membrane component).

• Humans: Synthesize cholesterol, not ergosterol.

• Example: Miconazole (Monistat) treats yeast infections.

Inhibition of Metabolic Pathways

Drugs can block essential metabolic reactions in pathogens.

• Sulfonamides: Block nucleotide synthesis by preventing folic acid synthesis.

• Mechanism: Sulfonamides compete with para-aminobenzoic acid (PABA) for the active site of the enzyme, inhibiting folic acid production.

Equation:

$\text{PABA} + \text{Enzyme} \rightarrow \text{Folic acid}$

$\text{Sulfonamide} + \text{Enzyme} \nrightarrow \text{Folic acid}$

Inhibition of Nucleic Acid Synthesis

Some drugs interfere with DNA or RNA synthesis, often used against viruses.

• Base analogs: Molecules resembling nucleotides but disrupt nucleic acid synthesis.

• Examples:

  • Ribavirin: Stops RNA synthesis (used for respiratory syncytial virus)

  • Acyclovir: Stops DNA synthesis (used for varicella zoster, herpes viruses)

Inhibition of Attachment/Entry

Antiviral drugs can prevent viruses from attaching to or entering host cells.

• Attachment inhibitors: Block viral binding to host cell receptors (e.g., T20 for HIV).

• Fusion inhibitors: Prevent fusion of viral and host membranes (e.g., RAFIs for hepatitis C and herpes simplex viruses).

Narrow vs. Broad Spectrum Antimicrobial Drugs

Definitions and Comparison

Antimicrobial drugs vary in the range of pathogens they target.

• Narrow-spectrum: Target a limited range of pathogens.

  • Pro: Highly effective against specific organisms.

  • Con: Limited applications.

• Broad-spectrum: Target many types of pathogens.

  • Pro: Useful for mixed or unknown infections.

  • Con: Can cause opportunistic (secondary) infections due to loss of microbial antagonism (competition between resident microbiota and pathogens for space and nutrients).

Spectrum of Activity Table

The following table summarizes the spectrum of activity for selected antimicrobial drugs:

Drug	Prokaryotes	Eukaryotes	Viruses
Penicillins	Gram-positive bacteria	-	-
Tetracycline	Gram-positive & Gram-negative bacteria, Chlamydia, Rickettsia	-	-
Azoles	-	Fungi	-
Acyclovir	-	-	Herpes viruses
Sulfonamides	Broad (many bacteria)	-	-

Additional info: Broad-spectrum drugs may disrupt normal microbiota, leading to secondary infections such as Clostridioides difficile colitis.