Gram Positive Bacterial Compounds Are Capable Of Potentiating The Effects Of LPS

Amazoniac

Member
Joined
Sep 10, 2014
Messages
8,583
Location
Not Uganda
Rebels that picture yourselves going out on a fury freeing all caged birds that you encounter but then back out with the excuse that they wouldn't survive on their own;
Birdie;

Peptidoglycan and lipoteichoic acid in gram-positive bacterial sepsis: receptors, signal transduction, biological effects, and synergism. - PubMed - NCBI

“The resurgence of gram positive bacterial infections has marked a dramatic change in the prevalence pattern of nosocomial infections. Today, 50% of all cases of sepsis are caused by gram-positive bacteria (11, 13–15), and it is likely that this proportion will continue to rise in the years to come.”

“Peptidoglycan (PepG) and lipoteichoic acid (LTA) are two of the major cell wall components in gram-positive bacteria (Fig. 1). Both PepG and LTA have been shown to stimulate inflammatory responses in a number of in vivo and in vitro experimental models. This review focuses on these effects of PepG and LTA. Gram-positive bacteria also produce the membrane bound lipopeptides and some secrete exotoxins, such as staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin (TSST-1).”

“PepG, the main component of the gram-positive bacterial cell wall, is a heteropolymer consisting of a glycan backbone of alternating units of N-acetyl-glucosamine and N-acetylmuramic acid, with short peptides linked to the lactyl groups of the muramic acid moieties (Fig. 1). During gram-positive bacterial infections, PepG is released from the bacteria and can reach the systemic circulation (66). PepG can be detected in human plasma using the silkworm larvae plasma test (66, 67). Some antibiotics may enhance the release of PepG (60- to 85-fold) and LTA (4- to 9-fold) from S. aureus in culture (68). Recent data suggest that during ethanol- or hemorrhageinduced intestinal injury, PepG can translocate from the intestine to the systemic circulation (69, 70).”

“..It was found that PepG induced the release of TNF with similar kinetics to that induced by LPS, and 1 _g of PepG per milliliter of culture medium was required to induce the release of immuno-detectable amounts of TNF.”

“Together these findings showed that PepG, like LPS, induces the production of several inflammatory cytokines associated with sepsis, and that the macroscopic structure of the PepG polymer is an intrinsic feature of its inflammatory properties.”

“In another study on human monocytes, serum components were found to potentiate the PepG-induced release of TNF-a (78). In the presence of 10% serum, low concentrations of PepG (0.01 to 0.1 microg/mL) induced the formation of TNF-a with potency similar to the one of LPS.”

“It has been argued that PepG is not an important initiator of inflammatory responses because cellular responses to this wall component typically require concentrations of 1–10 microg/mL, which is several logs higher than the concentrations of LPS required for activating macrophages. This may either mean that PepG is not an important initiator of inflammation or that only a part of the PepG structure is responsible for its proinflammatory properties. Although there seems to be some support for the latter (89), it should be noted that the structure–activity relationship of the interactions of PepG with pathogen recognition receptors is not yet fully understood. PepG is insoluble in its native form (90), but may be enzymatically cleaved into smaller components in vivo and in vitro.”

“Results from these experiments demonstrate that cross-linked sugar chains with at least three stem peptides were 100-fold more potent that undigested PepG, whereas simple stem peptides were largely inactive. In fact, such branched peptides representing less than 2% of the naïve PepG induced the release of TNF-a with similar potency to LPS (89).”

“LTA is a cell wall component unique to gram-positive bacteria, and belongs to a diverse class of sugar phosphate polymers, which contain an acyl group anchored to the cell membrane (Fig. 1). A nonacylated form of LTA, teichoic acid (TA), is covalently linked to PepG in the gram-positive bacterial cell wall.”

“..These studies suggest that LTA shares many properties with LPS. However, LPS is the most potent microbial structure that exists, and several logs higher concentrations of LTA are required to obtain the same TNF-a response.”

“Together these findings suggest that the inflammatory properties of LTA are strongly suppressed by normal serum, and that LTA alone is probably not an important initiator of inflammation in blood.”

“Recent data also demonstrate that PGRPs mediate activation of the NF-kB analogue relish (148) and an immune defense against gram-negative bacteria in Drosophila (149).”

“It is becoming increasingly clear that LPS cannot fully reproduce all clinical features of sepsis. This implies that other contributing factors co-operate with LPS to trigger the aberrant signaling events leading to sepsis and organ injury. It was noted more than 20 years ago that the synthetic PepG monomer MDP can act as an adjuvant and enhance immune responses (177–180). For example, Pabst and co-workers showed that pre-treatment of mouse peritoneal macrophages with MDP or LPS primed the cells for enhanced production of superoxide anions (O2−) in response to phorbol myristate acetate (PMA). The priming effect was not observed with stereo-isomers of MDP (178). It was also demonstrated that intravenous injection of MDP enhanced lethal toxicity of LPS in mice (181–183).”

“The priming effect of MDP in vitro is enhanced by IFN-y (184). Parant and colleagues reported that MDP and LPS act synergistically to induce TNF-a in mice, and maximal effect was noted when MDP was given several hours before LPS (185). It should be stressed that there is good evidence that MDP alone is unable to induce inflammatory cytokine production in cells (76). Thus, MDP and LPS interact in a synergistic manner to enhance inflammatory responses in-vitro and in-vivo, and cytokines may contribute to the consequences of such interactions. However, the molecular basis for this phenomenon is still unknown.”

“The implication of interactions between PepG and LTA on the pathophysiology of septic shock and multiple organ failure has been studied in our laboratory (99, 103). In one study it was demonstrated that infusion of PepG and phenol-extracted LTA cause shock and multiple organ failure in the anaesthetized rat, whereas each component alone was unable to do so.”

“..the potential effect of contamination with LPS in the commercial preparations of LTA (107, 108) has not been accounted for. This opens the possibility that the observed priming could be due to contaminating LPS in the LTA preparation, and not caused by LTA itself. In keeping with this notion, we have recently demonstrated that LPS and PepG act synergistically to cause organ failure and shock in the rat (187).”

“We also demonstrated that, in clear opposition to LPS, PepG causes increased expression of the CD14 receptor on the surface of monocytes (135, 136). Increased expression of CD14 induced by PepG may sensitize cellular responses to LPS, and thus be implicated in the increased sensitivity to LPS caused by PepG.”

“On the other hand, since both LPS and PepG bind to the CD14 receptor (47, 131), they would be expected to compete for CD14 occupancy and act as reciprocally inhibitors, rather than to act synergistically.”

As always, questions should be addressed to burtlancast via PM with a love note attached.
 
Last edited:

Elie

Member
Forum Supporter
Joined
Oct 30, 2015
Messages
815
I see this is an old post that no no one engaged with. I wonder if there is data on "good" gram positive bacteria such as Acidophilus and bifidus.
 

Broken man

Member
Joined
Sep 11, 2016
Messages
1,693
There is alot of studies showing opposite. Its not easy to find the truth.
 

Elie

Member
Forum Supporter
Joined
Oct 30, 2015
Messages
815
Well, @haidut, published a post about "all gut bacteria" but, is there evidence that the two most commonly promoted as healthy gram positive species are in fact harmful?
 

Similar threads

Back
Top Bottom