Controlling Microbial Growth in the Body

Introduction

This section explores the principles and mechanisms by which antimicrobial drugs control microbial growth within the human body. It covers definitions, 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 specifically used to treat infections. Example: antibiotics.

Example: Antibiotics are both chemotherapeutic and antimicrobial drugs because they treat infectious diseases.

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: Drugs must be more toxic to the pathogen than to the host.

• Implications:

  • Many antibacterial drugs exist because bacteria are prokaryotes and differ significantly from human cells.

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

  • Very few antiviral drugs exist because viruses use host cell machinery for replication, making selective targeting difficult.

Example: Penicillin targets bacterial cell wall synthesis, a process absent in human cells.

Mechanisms of Action of Antimicrobial Drugs

Overview

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

• Inhibition of cell wall synthesis (e.g., penicillins, cephalosporins)

• Inhibition of protein synthesis (e.g., streptomycin, tetracycline, erythromycin)

• Disruption of cytoplasmic membranes (e.g., azoles)

• Inhibition of metabolic pathways (e.g., sulfonamides)

• Inhibition of nucleic acid synthesis (e.g., ribavirin, acyclovir)

• Inhibition of attachment/entry (e.g., T20, RAFIs)

Inhibition of Bacterial Cell Wall Synthesis

Beta-lactam Antibiotics

Beta-lactam antibiotics contain a critical β-lactam ring and target enzymes involved in cell wall synthesis.

• Examples: Penicillins (natural), methicillin (semisynthetic), cephalosporins (natural)

• Mechanism: Bind enzymes that form cross-bridges between N-acetylmuramic acid (NAM) subunits, resulting in a weak cell wall and cell lysis.

Equation (structure of β-lactam ring):

Example: Penicillin inhibits transpeptidase, preventing peptidoglycan cross-linking.

Inhibition of Protein Synthesis

Targeting Ribosomes

Antimicrobial drugs exploit differences between prokaryotic and eukaryotic ribosomes.

• Prokaryotic ribosomes: 70S (composed of 30S and 50S subunits)

• Eukaryotic ribosomes: 80S (composed of 40S and 60S subunits)

• Examples:

  • Streptomycin binds 30S subunit, causing misreading of mRNA.

  • Tetracycline blocks tRNA binding to the 30S subunit.

  • Erythromycin binds 50S subunit, inhibiting translocation.

Example: Tetracycline prevents aminoacyl-tRNA from entering the ribosome, halting protein synthesis.

Disruption of Cytoplasmic Membranes

Azoles and Antifungals

Azoles are antifungal drugs that inhibit ergosterol synthesis, a key component of fungal cell membranes.

• Mechanism: Inhibit ergosterol synthesis; humans synthesize cholesterol instead.

• Example: Miconazole (Monistat) is used to treat yeast infections caused by Candida albicans.

Inhibition of Metabolic Pathways

Sulfonamides

Sulfonamides block nucleotide synthesis by preventing folic acid synthesis, which is essential for DNA and RNA production in bacteria.

• Mechanism: Sulfonamides are structural analogs of para-aminobenzoic acid (PABA) and competitively inhibit the enzyme involved in folic acid synthesis.

• Equation:

Example: Sulfonamide drugs are used to treat urinary tract infections.

Inhibition of Nucleic Acid Synthesis

Antiviral Drugs and Base Analogs

Drugs that inhibit nucleic acid synthesis are primarily used to treat viral infections by interfering with DNA or RNA replication.

• Base analogs: Molecules that resemble nucleic acid bases but disrupt replication.

• Examples:

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

  • Acyclovir: Stops DNA synthesis; used for Varicella zoster (chicken pox, shingles) and herpes virus infections.

Equation:

Inhibition of Attachment/Entry

Antiviral Strategies

Some antiviral drugs 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 virus, herpes simplex virus).

Example: T20 is used in HIV therapy to block viral entry into immune cells.

Narrow vs. Broad Spectrum Antimicrobial Drugs

Definitions, Advantages, and Disadvantages

Antimicrobial drugs vary in the range of pathogens they target.

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

  • Pro: Highly effective against specific organisms.

  • Con: Limited applications.

• Broad-spectrum drugs: Target a wide range of pathogens.

  • Pro: Useful for mixed infections or when the pathogen is unknown.

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

Example: Tetracycline is broad-spectrum, effective against many bacteria, but may cause secondary infections like yeast overgrowth.

Spectrum of Activity Table