Strategies for the control of LPS-mediated pathophysiological disorders

Chaby, Richard

doi:10.1016/s1359-6446(99)01336-7

Cited by 39 publications

(21 citation statements)

References 74 publications

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“…This pathology may lead to extensive injury of vascular endothelium, which often results in a more severe syndrome known as septic shock (Annane et al, 2005). About 50-60 % of septic shock episodes are related to infections by Gram-negative bacteria, and more concretely to the lipopolysaccharide (LPS or endotoxin), a major component of the bacterial outer membrane (Chaby, 1999). The human body is extremely sensitive to endotoxin and minimum amounts of this substance injected into it can cause serious effects to the system (e.g., fever, intravascular blood clotting and multiorgan failure) (Cohen, 2002).…”

Section: Introductionmentioning

confidence: 99%

Novel fully-integrated biosensor for endotoxin detection via polymyxin B immobilization onto gold electrodes

Zuzuarregui

Arana

Pérez-Lorenzo

et al. 2013

J. Sens. Sens. Syst.

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Abstract. In this paper an electrochemical endotoxin biosensor consisting of an immobilized lipopolysaccharide (LPS) ligand, polymyxin B (PmB), is presented. Several parameters involved both in the device fabrication and in the detection process were analyzed to optimize the ligand immobilization and the interaction between PmB and LPS, aiming at increasing the sensitivity of the sensor. Different electrochemical pre-treatment procedures as well as the functionalization methods were studied and evaluated. The use of a SAM (self-assembled monolayer) to immobilize PmB and the quantification of the interactions via cyclic voltammetry allowed the development of a robust and simple device for in situ detection of LPS. Thus, the biosensor proposed in this work intends an approach to the demanding needs of the market for an integrated, portable and simple instrument for endotoxin detection.

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Section: Introductionmentioning

confidence: 99%

Novel fully-integrated biosensor for endotoxin detection via polymyxin B immobilization onto gold electrodes

Zuzuarregui

Arana

Pérez-Lorenzo

et al. 2013

J. Sens. Sens. Syst.

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“…For most antimicrobial peptides that are not active against Gram-negative bacteria, the outer membrane is believed to be a major barrier (10,16,(22)(23)(24)(25)(26)(27)(28)(29). However, the details of the interactions of the peptides with these membranes are still not fully known (23, 30 -32).…”

mentioning

confidence: 99%

A Molecular Mechanism for Lipopolysaccharide Protection of Gram-negative Bacteria from Antimicrobial Peptides

Papo

Shai

2005

Journal of Biological Chemistry

226

218

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Cationic antimicrobial peptides serve as the first chemical barrier between all organisms and microbes. One of their main targets is the cytoplasmic membrane of the microorganisms. However, it is not yet clear why some peptides are active against one particular bacterial strain but not against others. Recent studies have suggested that the lipopolysaccharide (LPS) outer membrane is the first protective layer that actually controls peptide binding and insertion into Gram-negative bacteria. In order to shed light on these interactions, we synthesized and investigated a 12-mer amphipathic ␣-helical antimicrobial peptide (K 5 L 7 ) and its diastereomer (4D-K 5 L 7 ) (containing four D-amino acids). Interestingly, although both peptides strongly bind LPS bilayers and depolarize bacterial cytoplasmic membranes, only the diastereomer kills Gram-negative bacteria. Attenuated total reflectance Fourier transform infrared, CD, and surface plasmon resonance spectroscopies revealed that only the diastereomer penetrates the LPS layer. In contrast, K 5 L 7 binds cooperatively to the polysaccharide chain and the outer phosphate groups. As a result, the self-associated K 5 L 7 is unable to traverse through the tightly packed LPS molecules, revealed by epifluorescence studies with LPS giant unilamellar vesicles. The difference in the peptides' modes of binding is further demonstrated by the ability of the diastereomer to induce LPS miscellization, as shown by transmission electron microscopy. In addition to increasing our understanding of the molecular basis of the protection of bacteria by LPS, this study presents a potential strategy to overcome resistance by LPS, and it should help in the design of antimicrobial peptides for future therapeutic purposes.

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“…LPS stimulates several target cells to secrete active molecules. Examples include the response of neutrophilic granulocytes to LPS leading to the release of active oxygen species, as well as the production of inflammatory cytokines, such as TNF-· by monocytes and macrophages [5]. For LPS recognition, a binding protein/receptor system is required involving a LPSbinding protein, the glycoprotein CD14, and the Toll-like receptor-4, a CD14 coreceptor [6].…”

Section: Introductionmentioning

confidence: 99%

“…For LPS recognition, a binding protein/receptor system is required involving a LPSbinding protein, the glycoprotein CD14, and the Toll-like receptor-4, a CD14 coreceptor [6]. A number of PKs and PPs are implicated in LPS intracellular signal transduction indicating the important role of the phosphorylation state of critical phosphoproteins [5,7,8].…”

Section: Introductionmentioning

confidence: 99%

Michael Adducts of Palmitoylascorbic Acid: Effects on the Oxidative Burst of Neutrophils and the Production of Tumor Necrosis Factor-Alpha in Monocytes

Gütschow

Hauschildt

Benard³

et al. 2002

Pharmacology

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The effects of Michael adducts of 6-O-palmitoyl-L-ascorbic acid (compounds 1–4) on the phosphorylation-dependent response of stimulated monocytes and neutrophils was investigated. The pyranosyl derivative 3 increased the production of tumor necrosis factor-α in human monocytes stimulated with lipopolysaccharide (LPS). Compound 3 also enhanced the release of tumor necrosis factor-α from nonstimulated monocytes. Michael adducts 1–4 inhibited the formation of reactive oxygen species in fMLP-stimulated human neutrophils as measured by luminol chemiluminescence. Treatment with 6-O-palmitoyl-L-ascorbic acid (compound 5) also led to a decreased luminescence response of neutrophils. Results are discussed with respect to the inhibitory activity of Michael adducts of ascorbic acids towards protein phosphatases PP1/PP2A.

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Strategies for the control of LPS-mediated pathophysiological disorders

Cited by 39 publications

References 74 publications

Novel fully-integrated biosensor for endotoxin detection via polymyxin B immobilization onto gold electrodes

Novel fully-integrated biosensor for endotoxin detection via polymyxin B immobilization onto gold electrodes

A Molecular Mechanism for Lipopolysaccharide Protection of Gram-negative Bacteria from Antimicrobial Peptides

Michael Adducts of Palmitoylascorbic Acid: Effects on the Oxidative Burst of Neutrophils and the Production of Tumor Necrosis Factor-Alpha in Monocytes

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