Antibiotics Overview and Mechanisms

Antibiotic Action

• Antibiotics are chemical compounds made by microbes that selectively kill other microbes.
• Many are produced naturally, others are synthesized chemically.
• They exhibit Selective Toxicity, meaning they target bacterial physiology, not human physiology.
• Antibiotics target structures that are different in bacteria compared to eukaryotes like peptidoglycan, ribosomes, and DNA gyrase.

Antibiotic Spectrum of Activity

• Antibiotics are classified by their spectrum of activity, the types of organisms they affect:
  • Antibacterial (bacteria)
  • Antiprotozoal (single-celled eukaryotes)
  • Antiviral (viruses)
• Within antibacterial, antibiotics can have a narrow spectrum (specific bacteria) or a broad spectrum (multiple types of bacteria).

Bactericidal vs. Bacteriostatic Antibiotics

• Antibiotics are also classified as bactericidal (kill bacteria) or bacteriostatic (inhibit bacterial growth).
• Bacteriostatic antibiotics require the host's immune system to clear the infection.

Measuring Antibiotic Effectiveness

• Minimum Inhibitory Concentration (MIC) is the lowest concentration of an antibiotic that prevents bacterial growth.
• MIC is determined by serially diluting an antibiotic and inoculating bacteria into each dilution.
• Chemotherapeutic index is the ratio of the toxic dose to the therapeutic dose.
• A higher chemotherapeutic index indicates a safer drug.

Synergism and Antagonism

• Synergism occurs when two antibiotics used together have a greater effect than the sum of their individual effects.
• Antagonism occurs when two antibiotics interfere with each other, reducing their effectiveness.

Antibacterial Mechanisms of Action - Cell Wall Synthesis Inhibitors

• Beta-lactam antibiotics (e.g., penicillin) inhibit the synthesis of the bacterial cell wall by binding to penicillin-binding proteins (PBPs).
• PBPs are enzymes responsible for cross-linking peptidoglycan, a major component of the bacterial cell wall.
• Beta-lactams structurally resemble peptidoglycan and block PBP activity, leading to weakened cell walls and cell lysis.

Antibacterial Mechanisms of Action - DNA Synthesis Inhibitors

• Metronidazole (Flagyl) is a prodrug activated by anaerobic bacteria.
• It damages DNA by nicking it, leading to cell death.
• Metronidazole is effective against anaerobic bacteria like Bacteroides and Fusobacterium.
• Quinolones (e.g., ciprofloxacin, levofloxacin) inhibit DNA gyrase, an enzyme that unwinds DNA.
• Inhibition of DNA gyrase leads to accumulation of positive supercoils, preventing DNA replication and bacterial growth.

Antibacterial Mechanisms of Action - RNA synthesis Inhibitors

• Rifampin binds to bacterial RNA polymerase, preventing the synthesis of mRNA.
• This inhibits transcription and bacterial growth.
• Rifampin is used to treat tuberculosis and meningococcal meningitis.

Antibacterial Mechanisms of Action - Protein Synthesis Inhibitors

• Protein synthesis inhibitor target bacterial ribosomes and interfere with protein translation, which is essential for bacterial growth.
• These antibiotics are often bacteriostatic, meaning they inhibit growth rather than causing immediate death.
• These inhibitors bind to bacterial rRNA, which differs from eukaryotic rRNA, enabling selective toxicity.

This quiz explores the fundamentals of antibiotics, including their action, spectrum of activity, and classification as bactericidal or bacteriostatic. Understand how antibiotics selectively target microbes and their significance in medicine. Test your knowledge on the different types and their mechanisms of action.