SM

Gram-Positive vs. Gram-Negative Cell Walls and Related Antibiology

Gram-Positive Cell Wall

  • Thick, multilayered peptidoglycan structure

    • Can contain up to 40 distinct layers of peptidoglycan

  • Bacteria examples

    • Staphylococcus aureus (general staphylococcal spp.)

    • Streptococcus pyogenes (main etiologic agent of “strep throat”)

  • Gram-stain outcome: cells retain crystal-violet → appear purple

  • Architecture

    • Innermost plasma (cytoplasmic) membrane

    • Periplasmic space (very narrow) between membrane and peptidoglycan

    • No outer membrane; therefore no lipopolysaccharide (LPS)

Gram-Negative Cell Wall

  • More complex, multilayer system

  • Core layers

    • Plasma membrane (same location as in Gram-positive)

    • Thin peptidoglycan sheet (≈ 1–2 layers)

    • Unique outer membrane (absent in Gram-positive)

  • Outer membrane characteristics

    • Phospholipid bilayer analogous to plasma membrane, but external

    • Embedded lipopolysaccharide (LPS)

    • Green “tree-like” structures in diagrams

    • Also called endotoxin

      • When released in large quantities → high risk of septic shock

  • Gram-stain outcome: fails to retain crystal-violet → counterstains pink/red

Antibiotics & Selective Toxicity

  • Peptidoglycan as a major therapeutic target

    • Absent in human (eukaryotic) cells → excellent selective toxicity

  • Classic cell-wall–synthesis inhibitors (most effective vs. Gram-positives)

    • Penicillins

    • Vancomycin

    • Cephalosporins (all generations)

  • Limited efficacy of these drugs against Gram-negatives

    • Drug must traverse the outer membrane to reach thin peptidoglycan layer

    • Outer membrane acts as permeability barrier → decreased access

  • Alternative drug classes for Gram-negative infections

    • Agents targeting protein synthesis (e.g., aminoglycosides, tetracyclines)

    • Agents targeting DNA replication/transcription (e.g., fluoroquinolones)

Key Comparative Points

  • Plasma membrane: present in both Gram types

  • Peptidoglycan

    • Gram-positive: thick (≈ 40 layers), primary structural component

    • Gram-negative: thin (≈ 1–2 layers)

  • Outer membrane

    • Present only in Gram-negative bacteria

  • LPS / Endotoxin

    • Only in Gram-negative outer membrane; clinically linked to septic shock

  • Antibiotic implications

    • Gram-positive infections: cell-wall inhibitors highly effective

    • Gram-negative infections: require drugs able to bypass/penetrate outer membrane or target internal processes