Lipoteichoic acid (LTA) is a surface-associated adhesion amphiphile from Gram-positive bacteria and regulator of autolytic wall enzymes (muramidases). It is released from the bacterial cells mainly after bacteriolysis induced by lysozyme, cationic peptides from leucocytes, or beta-lactam antibiotics.

LTA may bind to target cells non-specifically through membrane phospholipids, or specifically to CD14 and to Toll-like receptors. Binding to TLR-2 has shown to induce NF-kB expression(a central transcription factor), elevating expression of both pro- and anti-apoptotic genes. Its activation also induces mitogen-activated protein kinases (MAPK) activation along with Phosphoinositide 3-kinase activation.

LTA bound to targets can interact with circulating antibodies and activate the complement cascade to induce a passive immune kill phenomenon. It also triggers the release from neutrophils and macrophages of reactive oxygen and nitrogen species, acid hydrolases, highly cationic proteinases, bactericidal cationic peptides, growth factors, and cytotoxic cytokines, which may act in synergy to amplify cell damage. Therefore, LTA shares many pathogenic similarities with endotoxins (lipopolysaccharide).

Studies on Lipoteichoic acid

In animal studies, LTA has induced arthritis, nephritis, uveitis, encephalomyelitis, meningeal inflammation, and periodontal lesions, and also triggered cascades resulting in septic shock and multiorgan failure. Binding of LTA to targets can be inhibited by phospholipids and antibodies directed at LTA, CD14, or Toll-like receptors. In vitro, LTA release can be inhibited by non-bacteriolytic antibiotics and by polysulphates such as heparin.

LTA can be considered a virulence factor that has an important role in infections and in postinfectious sequelae caused by Gram-positive bacteria. The development of effective antibacteriolitic drugs and multidrug strategies to attenuate LTA-induced secretion of proinflammatory agonists is of great importance to combat septic shock and multiorgan failure caused by Gram-positive bacteria.

References

• Department of Oral Biology, Hebrew University-Hadassah Faculty of Dental Medicine, Ein-Kerem Campus, Jerusalem, Israel.

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