antibiotic

Gram-Negative Bacteria and Antibiotic Resistance

• Gram-negative bacteria possess an outer membrane that makes it more difficult for certain antibiotics to penetrate.

• Some patients may experience allergic reactions to antibiotics like penicillin, prompting the use of alternatives such as vancomycin.

• Vancomycin is often employed as a last resort drug in treating serious infections, especially those caused by MRSA (Methicillin-resistant Staphylococcus aureus) and C. diff (Clostridium difficile).

• Overuse of these potent antibiotics contributes to the rise of antibiotic resistance.

Protein Synthesis Inhibitors

• Protein synthesis inhibitors are critical in targeting the ribosomes of bacteria to prevent protein production.

• The ribosome structure is divided into two subunits: 30S and 50S.

• Key drugs include:

  • Streptomycin: Alters the shape of the 30S subunit, impairing its function.

  • Tetracyclines: Prevent tRNA from binding, leading to the inability to produce proteins.

  • Macrolides (e.g., Chloramphenicol): Bind to the 50S subunit and inhibit the formation of peptide bonds between amino acids, preventing chain elongation of proteins.

Disruptors Of Membrane Integrity

• Certain antibiotics act as disruptors by creating pores in bacterial membranes, which differ from cell walls.

• Formation of these pores allows contents of the bacterial cell to leak out, disrupting cellular integrity, potentially leading to cell death.

• Selective toxicity: These drugs target bacterial cells specifically without affecting human cells because humans lack these pore-forming structures.

Metabolic Pathway Inhibitors

• Folate inhibitors are a specific class of antibiotics targeting bacterial metabolic pathways.

• The drug sulfonamides inhibits the enzyme involved in synthesizing folate from PABA (p-aminobenzoic acid), disrupting nucleic acid synthesis.

• Selective toxicity: Humans do not synthesize their own folate in the same manner as bacteria, minimizing side effects on human cells.

Transcription and Translation Mechanisms

• The central dogma of molecular biology describes the flow of genetic information: DNA → RNA → Protein.

• Drugs that affect this process include:

  • Rifampin: Targets bacterial RNA polymerase, important in transcription, especially used for tuberculosis.

  • Fluoroquinolones (e.g., Ciprofloxacin): Inhibit DNA gyrase, preventing DNA from properly supercoiling, thus affecting replication.

• Selective toxicity: The target enzymes in bacteria are substantially different from those in eukaryotic cells, reducing potential harm to human cells, although caution is advised due to similarities in mitochondrial DNA.

Conclusion: Addressing Antibiotic Resistance

• There is significant concern regarding antibiotic resistance, especially as patients are frequently prescribed antibiotics in short courses (e.g., 7-day treatments).

• Awareness of how different antibiotics work and the mechanisms of resistance can improve treatment efficacy and minimize the development of resistant bacterial strains.