Peptidoglycan and Lipoteichoic Acid in Gram-Positive Bacterial Sepsis: Receptors, Signal Transduction, Biological Effects, and Synergism

  title={Peptidoglycan and Lipoteichoic Acid in Gram-Positive Bacterial Sepsis: Receptors, Signal Transduction, Biological Effects, and Synergism},
  author={Jacob E. Wang and Maria Krudtaa Dahle and Michelle Craig McDonald and Simon J. Foster and Ansgar Oddne Aasen and Christoph Thiemermann},
In sepsis and multiple organ dysfunction syndrome (MODS) caused by gram-negative bacteria, lipopolysaccharide (LPS) initiates the early signaling events leading to the deleterious inflammatory response. However, it has become clear that LPS can not reproduce all of the clinical features of sepsis, which emphasize the roles of other contributing factors. Gram-positive bacteria, which lack LPS, are today responsible for a substantial part of the incidents of sepsis with MODS. The major wall… 


It is proposed that PepG must be regarded as an endotoxin in its own right and to encourage further work in the field of PepG signaling.

Lipoteichoic acids as a major virulence factor causing inflammatory responses via Toll-like receptor 2

An overview of LTA structure and host recognition by TLR2 that leads to the activation of innate immune responses is provided and emphasis is placed on differential immunostimulating activities of LTAs of various Gram-positive bacteria at the molecular level.

Targeting of key pathogenic factors from gram-positive bacteria by the soluble ectodomain of the scavenger-like lymphocyte receptor CD6.

The potential use of a soluble form of the scavenger-like human lymphocyte receptor CD6 (shCD6) belonging to an ancient family of innate immune receptors in the treatment of severe gram-positive-induced infectious conditions is evaluated.

Anti-inflammatory effects of clenbuterol on equine leukocytes stimulated ex vivo with bacterial toxins

Therapeutic agents targeting leukocyte activation may have actions complimentary to those of non-steroidal anti-inflammatory drugs in the treatment of systemic inflammation in horses, and the β2-adrenoreceptor agonist drug clenbuterol hydrochloride may be effective in reducing equine leukocytes activation and cytokine production.

Antimicrobial peptides: the LPS connection.

A mix of antimicrobial, LPS-sequestering/neutralization, and immunomodulatory features make cationic peptides, and especially synthetic or semi-synthetic amphiphilic compounds built on their scheme, attractive candidates for novel drugs to be administered in antisepsis therapies.

Activation of cytokine synthesis by systemic infusions of lipopolysaccharide and peptidoglycan in a porcine model in vivo and in vitro.

Peptidoglycan and LPS synergized to increase the formation of the proinflammatory cytokine TNF-alpha in this large animal model and could be of importance for the signs and symptoms of sepsis.

Staphylococcal LTA antagonizes the B cell-mitogenic potential of LPS

Results support that Staphylococcus aureus LTA inhibited LPS-induced B cell proliferation through the decrease of ERK phosphorylation via TLR2 signaling pathway.

Monocyte and Macrophage Activation by Lipoteichoic Acid Is Independent of Alanine and Is Potentiated by Hemoglobin1

Hb-LTA-Hb interactions could occur during streptococcal infections and might result in a profound alteration of the local inflammatory response.



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

The 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.

Mechanism of Gram-positive Shock: Identification of Peptidoglycan and Lipoteichoic Acid Moieties Essential in the Induction of Nitric Oxide Synthase, Shock, and Multiple Organ Failure

It is proposed that the structure of LTA determines the ability of a particular bacterium to cause shock and multiple organ failure (pathogenicity), while PepG acts to amplify any response induced by LTA.

A cell wall component from pathogenic and non-pathogenic gram-positive bacteria (peptidoglycan) synergises with endotoxin to cause the release of tumour necrosis factor-alpha, nitric oxide production, shock, and multiple organ injury/dysfunction in the rat.

Investigation of whether cell wall fragments from gram-positive and gram-negative bacteria could synergise to cause the release of cytokines, shock, and organ injury/ dysfunction in vivo found synergism between PepG and LPS may partly explain the high mortality associated with mixed bacterial infections.

Peptidoglycan- and Lipoteichoic Acid-induced Cell Activation Is Mediated by Toll-like Receptor 2*

It is shown that whole Gram-positive bacteria, sPGN and LTA induce the activation of NF-κB in HEK293 cells expressing TLR2 but not in cells expressingTLR1 or TLR4, which identifies TLR 2 as a signal transducer for sPGn and Lta in addition to LPS.


It is shown that PepG and LTA act synergistically to cause respiratory failure and septic shock in the pig and could serve as a new, well‐controlled model for studies of Gram‐positive sepsis.

Peptidoglycan primes for LPS-induced release of proinflammatory cytokines in whole human blood.

The data suggest that PepG and MDP primes human whole blood leukocytes for LPS-induced release of proinflammatory cytokines, and it is speculated that synergy between PepsiG and LPS may contribute to the pathogenesis in sepsis caused by mixed bacterial infections.

Antibiotic-Induced Release of Lipoteichoic Acid and Peptidoglycan from Staphylococcus aureus: Quantitative Measurements and Biological Reactivities

Enzymatic degradation of PG in the supernatant indicated that PG was mainly responsible for the observed biological reactivity, and the capacity of β-lactam supernatants to stimulate the production of tumor necrosis factor alpha and interleukin-10 in human whole blood was significantly higher than that of protein synthesis inhibitor or controlsupernatants.

Commercial Preparations of Lipoteichoic Acid Contain Endotoxin That Contributes to Activation of Mouse Macrophages In Vitro

The results indicate that commercially available LTA can contain contaminating and potentially significant levels of endotoxin that can be expected to contribute to the putative macrophage-stimulating effects of LTA as assessed by NO production.

Characteristics of surfactant protein A and D binding to lipoteichoic acid and peptidoglycan, 2 major cell wall components of gram-positive bacteria.

Results indicate that SP-D interacts with gram-positive bacteria via binding to the cell wall components LTA and PepG and that the carbohydrate recognition domain is responsible for this binding.

Lipoteichoic acid is a potent inducer of cytokine production in rat and human Kupffer cells in vitro.

The contention that gram-positive bacteria may activate cytokine production in Kupffer cells during bacteremia is supported and it is suggested that LTA is important in this interaction.