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