Lipopolysaccharide Neutralization by Cationic-Amphiphilic Polymers through Pseudoaggregate Formation

Uppu, Divakara S. S. M.; Haldar, Jayanta

doi:10.1021/acs.biomac.5b01567

Cited by 52 publications

(76 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neutralisation of LPS by these peptides, structurally related to PxB, is associated with a fluidisation of the LPS acyl chains and a dramatic change in the LPS aggregate type from cubic into multilamellar, with an increase in the aggregate size. Other groups of synthetic amphiphilic polymers with endotoxin-neutralising properties also bind and cause a pseudoaggregate formation, resulting in LPS neutralisation/detoxification [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

The Perturbation of Pulmonary Surfactant by Bacterial Lipopolysaccharide and Its Reversal by Polymyxin B: Function and Structure

Liskayová

Kanjaková

et al. 2018

IJMS

View full text Add to dashboard Cite

After inhalation, lipopolysaccharide (LPS) molecules interfere with a pulmonary surfactant, a unique mixture of phospholipids (PLs) and specific proteins that decreases surface tension at the air–liquid interphase. We evaluated the behaviour of a clinically used modified porcine pulmonary surfactant (PSUR) in the presence of LPS in a dynamic system mimicking the respiratory cycle. Polymyxin B (PxB), a cyclic amphipathic antibiotic, is able to bind to LPS and to PSUR membranes. We investigated the effect of PxB on the surface properties of the PSUR/LPS system. Particular attention was paid to mechanisms underlying the structural changes in surface-reducing features. The function and structure of the porcine surfactant mixed with LPS and PxB were tested with a pulsating bubble surfactometer, optical microscopy, and small- and wide-angle X-ray scattering (SAXS/WAXS). Only 1% LPS (w/w to surfactant PLs) prevented the PSUR from reaching the necessary low surface tension during area compression. LPS bound to the lipid bilayer of PSUR and disturbed its lamellar structure by swelling. The structural changes were attributed to the surface charge unbalance of the lipid bilayers due to LPS insertion. PxB acts as an inhibitor of structural disarrangement induced by LPS and restores original lamellar packing, as detected by polarised light microscopy and SAXS.

show abstract

Section: Discussionmentioning

confidence: 99%

The Perturbation of Pulmonary Surfactant by Bacterial Lipopolysaccharide and Its Reversal by Polymyxin B: Function and Structure

Liskayová

Kanjaková

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…The white solid was washed with diethyl ether (4 × 40 mL) and dried at 40°C for 6 h under vacuum. The characterization of the compounds has been described previously [ 28 – 31 ].…”

Section: Methodsmentioning

confidence: 99%

Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria

et al. 2017

Self Cite

View full text Add to dashboard Cite

Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin) to biofilms of Gram-negative bacteria. These molecules eliminate planktonic bacteria that are liberated after dispersion of biofilms (dispersed cells). The membrane-active mechanism of these molecules forms the key for potentiating the established antibiotics. Further, we demonstrate that the combination of macromolecules and antibiotics significantly reduces bacterial burden in mouse burn and surgical wound infection models caused by Acinetobacter baumannii and Carbapenemase producing Klebsiella pneumoniae (KPC) clinical isolate respectively. Colistin, a well-known antibiotic targeting the lipopolysaccharide (LPS) of Gram-negative bacteria fails to kill antibiotic tolerant cells and dispersed cells (from biofilms) and bacteria develop resistance to it. On the contrary, these macromolecules prevent or delay the development of bacterial resistance to known antibiotics. Our findings emphasize the potential of targeting the bacterial membrane in antibiotic potentiation for disruption of biofilms and suggest a promising strategy towards developing therapies for topical treatment of Gram-negative infections.

show abstract

“…LPS has been suspected to be a component of the pellicle extracellular matrix in A. baumannii (22). Consequently, the accumulation of proteins involved in its synthesis might favor the pellicle establishment and facilitate, via its amphiphilic nature, the initial cells attachment (88).…”

Section: Increase Of Drug Resistance and Stress Adaptation Proteins Bmentioning

confidence: 99%

Global Dynamic Proteome Study of a Pellicle-forming Acinetobacter baumannii Strain

Kentache

Araar

Jouenne

et al. 2017

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

For several decades, many bacteria, among which A. baumannii, have shown their ability to colonize the upper surface of static liquids, forming a biofilm at the air-liquid interface named pellicle. Despite the ubiquity of these pellicles in both natural and artificial environments, few studies have investigated this biofilm type. The present data set provides the first description of the whole proteome of A. baumannii cells grown as pellicle, using a label-free mass spectrometry approach. Results are in accord with the general findings reporting that sessile bacteria are far more resistant to detrimental conditions than their planktonic counterparts, by the accumulation of stress proteins. The present investigation also confirmed previous studies suggesting a correlation between the pellicle forming ability and the bacterial virulence. Indeed, we showed the up-regulation of numerous virulence factors during the pellicle growth, e.g. phospholipases, adhesion factors, as well as those of the GacAS Two-Component System (TCS) and Type 6 Secretion System (T6SS). We also highlighted that Bam and Tam systems, both related to the OM insertion machinery, play a critical role during pellicle biogenesis. Moreover, sessile bacteria activate several pathways, e.g. iron, magnesium, phosphate pathways, which allows for increasing the panel of nutrient sources. Molecular & Cellular Proteomics

show abstract

Lipopolysaccharide Neutralization by Cationic-Amphiphilic Polymers through Pseudoaggregate Formation

Cited by 52 publications

References 64 publications

The Perturbation of Pulmonary Surfactant by Bacterial Lipopolysaccharide and Its Reversal by Polymyxin B: Function and Structure

The Perturbation of Pulmonary Surfactant by Bacterial Lipopolysaccharide and Its Reversal by Polymyxin B: Function and Structure

Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria

Global Dynamic Proteome Study of a Pellicle-forming Acinetobacter baumannii Strain

Contact Info

Product

Resources

About