The Inhibition of Lipid A Biosynthesis—The Antidote Against Superbugs?

González‐Bello, Concepción

doi:10.1002/adtp.201800117

Cited by 6 publications

(2 citation statements)

References 91 publications

(226 reference statements)

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“…The central role of lipid A in the pathogenesis of sepsis makes it a good target for antibiotic strategies [26]. The central role of lipid A in the pathogenesis of sepsis makes it a good ta antibiotic strategies [26].…”

Section: Endotoxin: Structure and Characteristicsmentioning

confidence: 99%

Endotoxin in Sepsis: Methods for LPS Detection and the Use of Omics Techniques

et al. 2022

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Lipopolysaccharide (LPS) or endotoxin, the major cell wall component of Gram-negative bacteria, plays a pivotal role in the pathogenesis of sepsis. It is able to activate the host defense system through interaction with Toll-like receptor 4, thus triggering pro-inflammatory mechanisms. A large amount of LPS induces inappropriate activation of the immune system, triggering an exaggerated inflammatory response and consequent extensive organ injury, providing the basis of sepsis damage. In this review, we will briefly describe endotoxin’s molecular structure and its main pathogenetic action during sepsis. In addition, we will summarize the main different available methods for endotoxin detection with a special focus on the wider spectrum offered by omics technologies (genomics, transcriptomics, proteomics, and metabolomics) and promising applications of these in the identification of specific biomarkers for sepsis.

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Section: Endotoxin: Structure and Characteristicsmentioning

confidence: 99%

Endotoxin in Sepsis: Methods for LPS Detection and the Use of Omics Techniques

et al. 2022

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“…15 In the present study, the key enzymes in lipid A biosynthesis pathway which are essential for the cell wall synthesis and pathogenesis of bacteria cell were explored as drug target. 16 Lipid A biosynthesis pathway starts with acylation of UDP-N-acetylglucosamine (UDP-GlcNAc) with 3-hydroxymyristoate-acylcarrier-protein (3-OH-c14-ACP) to form UDP-3-O-acyl-N-acetylglucosamine (UDP-3-O-acylGlcNAc). This reaction is catalyzed by UDP-GlcNAc acyltransferase (LpxA) (Fig.…”

Section: Introductionmentioning

confidence: 99%

Pharmacoinformatics approaches to identify potential hits against tetraacyldisaccharide 4′-kinase (LpxK) ofPseudomonas aeruginosa

et al. 2020

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Molecular Architecture and Charging Effects Enhance the In Vitro and In Vivo Performance of Multi‐Arm Antimicrobial Agents Based on Star‐Shaped Poly(l‐lysine)

Lü

Quan

et al. 2019

Advanced Therapeutics

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Molecular architecture is a largely neglected and unexplored factor that could impart a significant difference to the antimicrobial activity of antimicrobial peptides. In this article, the advantages (i.e., improved charging effect and enhanced proteolytic stability) of star-shaped poly(l-lysine)s (PLLs) over their linear analogs are extensively explored by the methods of computational simulation and experiments. A series of PEI-g-PLL with a hyperbranched polyethylenimine (PEI) core and PLL peripheral chains are designed as a class of versatile molecular scaffold for the development of star-shaped antimicrobial peptides. Computational simulations and zeta-potential measurements reveal that the change in PLL conformation from linear to star-shaped significantly increases the cationic charge density, allowing enhanced binding affinity toward the bacterial membrane. The minimum inhibitory concentration and killing kinetics measurements demonstrate that PEI-g-PLLs exhibit higher antimicrobial activity and bactericidal efficiency in vitro than the linear PLL counterparts. The absence of hydrophobic segments in PEI-g-PLLs weakens the nonspecific interactions with eukaryotic cells and offers remarkable selectivity, as evidenced by their negligible hemolytic activity. Furthermore, PEI-g-PLLs demonstrate enhanced proteolytic stability and unprecedented antimicrobial activity in vivo. PEI-g-PLLs, with their high antimicrobial activity, enormous selectivity, and remarkable proteolytic stability, represent a new series of potent antimicrobial peptides to treat drug-resistant infections.

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The Inhibition of Lipid A Biosynthesis—The Antidote Against Superbugs?

Cited by 6 publications

References 91 publications

Endotoxin in Sepsis: Methods for LPS Detection and the Use of Omics Techniques

Endotoxin in Sepsis: Methods for LPS Detection and the Use of Omics Techniques

Pharmacoinformatics approaches to identify potential hits against tetraacyldisaccharide 4′-kinase (LpxK) ofPseudomonas aeruginosa

Molecular Architecture and Charging Effects Enhance the In Vitro and In Vivo Performance of Multi‐Arm Antimicrobial Agents Based on Star‐Shaped Poly(l‐lysine)

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