Lipopolysaccharides: structure, function and bacterial identification

Caroff, Martine; Новиков, А. В.

doi:10.1051/ocl/2020025

Cited by 46 publications

(37 citation statements)

References 57 publications

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“…Lipid A isolation and structural characterization: Lipid A isolation was performed as previously described [ 58 ] which was used for MALDI-TOF MS.…”

Section: Methodsmentioning

confidence: 99%

Colistin-phage combinations decrease antibiotic resistance in Acinetobacter baumannii via changes in envelope architecture

Wang

Loh

Altamirano

et al. 2021

Emerging Microbes & Infections

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Multidrug-resistant bacterial infections are becoming increasingly common, with only few last-resort antibiotics such as colistin available for clinical therapy. An alternative therapeutic strategy gaining momentum is phage therapy, which has the advantage of not being affected by bacterial resistance to antibiotics. However, a major challenge in phage therapy is the rapid emergence of phage-resistant bacteria. In this work, our main aim was to understand the mechanisms of phage-resistance used by the top priority pathogen Acinetobacter baumannii . We isolated the novel phage Phab24, capable of infecting colistin-sensitive and -resistant strains of A. baumannii . After co-incubating Phab24 with its hosts, we obtained phage-resistant mutants which were characterized on both genotypic and phenotypic levels. Using whole genome sequencing, we identified phage-resistant strains that displayed mutations in genes that alter the architecture of the bacterial envelope at two levels: the capsule and the outer membrane. Using an adsorption assay, we confirmed that phage Phab24 uses the bacterial capsule as its primary receptor, with the outer membrane possibly serving as the secondary receptor. Interestingly, the phage-resistant isolates were less virulent compared to the parental strains in a Galleria mellonella infection model. Most importantly, we observed that phage-resistant bacteria that evolved in the absence of antibiotics exhibited an increased sensitivity to colistin, even though the antibiotic resistance mechanism per se remained unaltered. This increase in antibiotic sensitivity is a direct consequence of the phage-resistance mechanism, and could potentially be exploited in the clinical setting.

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“…Lipid A isolation and structural characterization: Lipid A isolation was performed as previously described [ 58 ] which was used for MALDI-TOF MS.…”

Section: Methodsmentioning

confidence: 99%

Colistin-phage combinations decrease antibiotic resistance in Acinetobacter baumannii via changes in envelope architecture

Wang

Loh

Altamirano

et al. 2021

Emerging Microbes & Infections

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“…LPS is a large glycolipid composed of lipids and polysaccharides and is applied to induce intestinal barrier permeability [ 26 , 27 ]. We evaluated TEER values to investigate the potential protective effects of AE-GBE on Caco-2 cell monolayer barrier function.…”

Section: Resultsmentioning

confidence: 99%

Gryllus bimaculatus Extract Protects against Lipopolysaccharide-Derived Inflammatory Response in Human Colon Epithelial Caco-2 Cells

Kim

Park

Baek

et al. 2021

Insects

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Increased tight junction permeability and overproduction of proinflammatory cytokines are crucial pathophysiological mechanisms in inflammatory bowel disease (IBD). This study evaluated anti-inflammatory effects of aqueous ethanolic Gryllus bimaculatus extract (AE-GBE) against intestinal permeability on lipopolysaccharide (LPS)-treated Caco-2 cells. Treatment with AE-GBE increased cell viability and significantly reduced inflammatory mediators such as nitric oxide and LPS-induced reactive oxidative stress. LPS increased the expression levels of iNOS, Cox-2, and 4-hydroxylnonenal; however, these levels were attenuated by AE-GBE treatment. Moreover, the mRNA and protein expression levels of the inflammatory cytokines TNFα, IL-6, IL-1β, and IFNγ were increased by LPS, but were significantly reduced by AE-GBE treatment. Intestinal epithelial permeability and the related expression of the proteins Zoula ocludence-1, occludin, and claudin-1 was increased by LPS treatment, and this effect was significantly reduced by AE-GBE treatment. The reduction in AMPK phosphorylation in LPS-treated Caco-2 cells was reversed in activation by co-treatment with AE-GBE. In conclusion, AE-GBE can protect epithelial cells from LPS-induced impaired barrier integrity by increasing tight junction proteins and preventing various inflammatory mediators. Thus, AE-GBE has the potential to improve inflammation-related diseases, including IBD, by inhibiting excessive production of inflammation-inducing mediators.

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“…Lipid A is the active component of lipopolysaccharides (also called endotoxins) found in the outer membrane of most gram-negative bacteria [ 1 ]. On the one hand, lipid A has been known to affect the immune system, as it is an immunostimulant capable of inducing a protective, non-specific immune response in the host.…”

Section: Introductionmentioning

confidence: 99%

Study on the CID Fragmentation Pathways of Deprotonated 4’-Monophosphoryl Lipid A

2021

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Lipid A, the membrane-bound phosphoglycolipid component of bacteria, is held responsible for the clinical syndrome of gram-negative sepsis. In this study, the fragmentation behavior of a set of synthetic lipid A derivatives was studied by electrospray ionization multistage mass spectrometry (ESI-MSn), in conjunction with tandem mass spectrometry (MS/MS), using low-energy collision-induced dissociation (CID). Genealogical insight about the fragmentation pathways of the deprotonated 4’-monophosphoryl lipid A structural analogs led to proposals of a number of alternative dissociation routes that have not been reported previously. Each of the fragment ions was interpreted using various possible mechanisms, consistent with the principles of reactions described in organic chemistry. Specifically, the hypothesized mechanisms are: (i) cleavage of the C-3 primary fatty acid leaves behind an epoxide group attached to the reducing sugar; (ii) cleavage of the C-3’ primary fatty acid (as an acid) generates a cyclic phosphate connected to the nonreducing sugar; (iii) cleavage of the C-2’ secondary fatty acid occurs both in acid and ketene forms; iv) the C-2 and C-2’ primary fatty acids are eliminated as an amide and ketene, respectively; (v) the 0,2A2 cross-ring fragment contains a four-membered ring (oxetanose); (vi) the 0,4A2 ion is consecutively formed from the 0,2A2 ion by retro-aldol, retro-cycloaddition, and transesterification; and (vii) formations of H2PO4− and PO3− are associated with the formation of sugar epoxide. An understanding of the relation between 0,2A2 and 0,4A2-type sugar fragments and the different cleavage mechanisms of the two ester-linked primary fatty acids is invaluable for distinguishing lipid A isomers with different locations of a single ester-linked fatty acid (i.e., at C-3 or C-3’). Thus, in addition to a better comprehension of lipid A fragmentation processes in mass spectrometers, our observations can be applied for a more precise elucidation of naturally occurring lipid A structures.

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Lipopolysaccharides: structure, function and bacterial identification

Cited by 46 publications

References 57 publications

Colistin-phage combinations decrease antibiotic resistance in Acinetobacter baumannii via changes in envelope architecture

Colistin-phage combinations decrease antibiotic resistance in Acinetobacter baumannii via changes in envelope architecture

Gryllus bimaculatus Extract Protects against Lipopolysaccharide-Derived Inflammatory Response in Human Colon Epithelial Caco-2 Cells

Study on the CID Fragmentation Pathways of Deprotonated 4’-Monophosphoryl Lipid A

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