The cell wall components peptidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure.

Abstract

Although the incidence of Gram-positive sepsis has risen strongly, it is unclear how Gram-positive organisms (without endotoxin) initiate septic shock. We investigated whether two cell wall components from Staphylococcus aureus, peptidoglycan (PepG) and lipoteichoic acid (LTA), can induce the inflammatory response and multiple organ dysfunction syndrome (MODS) associated with septic shock caused by Gram-positive organisms. In cultured macrophages, LTA (10 jig/ml), but not PepG (100 'g/ml), induces the release of nitric oxide measured as nitrite. PepG, however, caused a 4-fold increase in the production of nitri$e elicited by LTA. Furthermore, PepG antibodies inhibited the release of nitrite elicited by killed S. aureus. Administration of both PepG (10 mg/kg; i.v.) and LTA (3 mg/kg; i.v.) in anesthetized rats resulted in the release of tumor necrosis factor et and interferon -y and MODS, as indicated by a decrease in arterial oxygen pressure (lung) and an increase in plasma concentrations of bilirubin and alanine aminotransferase (liver), creatinine and urea (kidney), lipase (pancreas), and creatine kinase (heart or skeletal muscle). There was also the expression of inducible nitric oxide synthase in these organs, circulatory failure, and 50% mortality. These effects were not observed after administration of PepG or LTA alone. Even a high dose of LTA (10 mg/kg) causes only circulatory failure but no MODS. Thus, our results demonstrate that the two bacterial wall components, PepG and LTA, work together to cause systemic inflammation and multiple systems failure associated with Gram-positive organisms.

Lactobacillus plantarum Lipoteichoic Acid Alleviates TNF-α-Induced Inflammation in the HT-29 Intestinal Epithelial Cell Line

“…LTA is a cell wall component of Gram-positive bacteria that has numerous biological functions including neutrophil recruitment, impairment of osteoclastogenesis, and induction of inflammation in the mammary gland and lung. It also causes septic shock and multiorgan failure (Bougarn et al, 2010;De Kimpe et al, 1995;Knapp et al, 2008;Rainard et al, 2008;Yang et al, 2009). LTA plays important roles in both innate and adaptive immunity (Chan et al, 2007;Kim et al, 2007b;Seo et al, 2008).…”

Lipoteichoic Acid Isolated from Lactobacillus plantarum Inhibits Lipopolysaccharide-Induced TNF-α Production in THP-1 Cells and Endotoxin Shock in Mice

“…However, most bacterial cell walls used in tolerance-induction tests were isolated from pathogenic bacteria, making them harmful for use in clinical applications. The reason for this is that it is difficult to decide the proper concentration to induce the tolerance, and the composition of these bacterial cell walls can cause synergistical inflammation or septic shock (17,18). In our present experiments, the treatment of LPS or aLTA in THP-1 cells induced excessive proinflammatory cytokine production, and the mouse survival rate was reduced by 50% in the LPS-induced tolerance as compared with endotoxin shock mice, indicating the risk of pathogenic bacterial cell walls as a clinical material.…”

Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors

“…Thus for the GRAIP output, a minimum possible P value with 50,000 permutations is 0.00002 (1/50,000), so the maximum −log P is 4. 22 (Il22), which play substantial roles in mucosal immunity, where they shape T cell development and elicit antibacterial responses in intestinal epithelial cells (33,34). Lactococci have only recently been observed in the GI tract through pyrosequencing data, but members of the Coriobacteriaceae (e.g., Eggerthella, Enterorhabdus) are associated with mouse models of inflammatory disease (35,36).…”