teichoic acid

**Structure** - Polymers of glycerol phosphate or ribitol phosphate, often modified with D-alanine, glucose, or N-acetylglucosamine. The phosphates give them a net negative charge. - Two types: 1. **Wall teichoic acid (WTA):** covalently linked to the peptidoglycan (N-acetylmuramic acid). 2. **Lipoteichoic acid (LTA):** anchored to the cytoplasmic membrane by a glycolipid and extends through the peptidoglycan layer. - Found **only in gram-positive bacteria**. Gram-negative bacteria have LPS (endotoxin) in the outer membrane instead.

**Functions** - Maintain cell wall structure and rigidity, and regulate autolysins. - Bind and concentrate cations (Mg²⁺, Ca²⁺) and help with ion homeostasis. - Mediate adherence and colonization. For example, LTA of *S. pyogenes* helps it attach to pharyngeal epithelium, and WTA of *S. aureus* helps it attach to nasal epithelium. - Contribute to biofilm formation and antibiotic resistance. D-alanylation of teichoic acids reduces susceptibility to cationic antimicrobial peptides and to vancomycin/daptomycin.

**Clinical significance** - **Immune activation:** LTA and peptidoglycan are recognized by **TLR2** (with TLR1 or TLR6). This triggers NF-κB signaling and release of IL-1, IL-6, and TNF-α. This is the gram-positive counterpart of LPS/TLR4 activation and contributes to gram-positive septic shock. - **Antigenicity:** WTA is a target for antibodies, and the group C carbohydrate of streptococci is a similar cell wall polysaccharide. - ***S. aureus*:** WTA is a major adhesin and virulence factor. WTA-based antibodies and vaccines are being studied. - **Drug targets:** vancomycin and β-lactams act on peptidoglycan synthesis. Inhibitors of WTA synthesis (e.g., tunicamycin, targocil) can resensitize MRSA to β-lactams in experimental settings.

**High-yield comparison (gram-positive vs. gram-negative)**

| Feature | Gram-positive | Gram-negative | |---|---|---| | Peptidoglycan | Thick | Thin | | Teichoic acid | Present | Absent | | Outer membrane/LPS | Absent | Present | | Periplasmic space | Absent/minimal | Present |

**Board pearls** - "Teichoic acid = gram-positive only"; LPS/lipid A = gram-negative only. - Teichoic acids and peptidoglycan activate TLR2. LPS activates TLR4 (with CD14 and MD-2). - Lipoteichoic acid is the gram-positive "endotoxin-like" molecule, but it is generally a weaker inducer of shock than LPS. - Mycobacteria have mycolic acids and arabinogalactan instead and are not classically stained by Gram stain.