Dataset Information

Glucose-Induced Cyclic Lipopeptides Resistance in Bacteria via ATP Maintenance through Enhanced Glycolysis.

ABSTRACT: Cyclic lipopeptide (CLP) antibiotics have a mechanism that causes membrane malfunction. Thus mechanisms of bacterial resistance to CLPs are thought to modify cell surfaces. However, we found that bacterial resistance to CLPs was strongly related to energy metabolism. Using polymyxin B (PB) as a model of CLPs, we showed that PB causes malfunction of respiration and serious depletion of ATP, contributing to PB-induced cell death and carbon starvation. Glucose addition could maintain the intracellular ATP level and reverse the carbon starvation response resulting from PB treatment. Another study revealed that glycolysis was stimulated by the presence of PB and glucose. The mechanism underlying glucose-enabled CLPs' resistance suggests that glucose could maintain the ATP level in PB-treated bacteria by enhancing glycolysis. Similar results were observed in Staphylococcus aureus, where daptomycin resistance was enhanced by glucose. These findings provide insight into the mode of action of CLPs and resistance to these antibiotics.

SUBMITTER: Yu WB

PROVIDER: S-EPMC6820274 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Glucose-Induced Cyclic Lipopeptides Resistance in Bacteria via ATP Maintenance through Enhanced Glycolysis.

Yu Wen-Bang WB Pan Qian Q Ye Bang-Ce BC

iScience 20191007

Cyclic lipopeptide (CLP) antibiotics have a mechanism that causes membrane malfunction. Thus mechanisms of bacterial resistance to CLPs are thought to modify cell surfaces. However, we found that bacterial resistance to CLPs was strongly related to energy metabolism. Using polymyxin B (PB) as a model of CLPs, we showed that PB causes malfunction of respiration and serious depletion of ATP, contributing to PB-induced cell death and carbon starvation. Glucose addition could maintain the intracellu ...[more]

PMID: 31655254

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Project description:Cyclic lipopeptides (CLiPs) have many biological functions, including the selective permeabilization of target membranes, and technical and medical applications. We studied the anionic CLiP viscosin from Pseudomonas along with a neutral analog, pseudodesmin A, and the cationic viscosin-E2K to better understand electrostatic effects on target selectivity. Calcein leakage from liposomes of anionic phosphatidylglycerol (PG) and phosphatidylethanolamine (PE) is measured in comparison with net-neutral phosphatidylcholine by time-resolved fluorescence. By contrast to the typical selectivity of cationic peptides against anionic membranes, we find viscosin more active against PG/PE at 30 μM lipid than viscosin-E2K. At very low lipid concentration, the selectivity is reversed. An equi-activity analysis reveals the reciprocal partition coefficients, 1/K, and the CLiP-to-lipid mole ratio within the membrane as leakage after 1 h reaches 50%, Re50. As expected, 1/K to PG/PE is much lower (higher affinity) for viscosin-E2K (3 μM) than viscosin (15 μM). However, the local damage to the PG/PE membrane caused by a viscosin molecule is much stronger than that of viscosin-E2K. This can be explained by the strong membrane expansion due to PG/viscosin repulsion inducing asymmetry stress between the two leaflets and, ultimately, transient limited leakage at Re50 = 0.08. PG/viscosin-E2K attraction opposes expansion and leakage starts only as the PG charges in the outer leaflet are essentially compensated by the cationic peptide (Re50 = 0.32). In the high-lipid regime (at lipid concentrations cL ≫ 1/K), virtually all CLiP is membrane bound anyway and Re50 governs selectivity, favoring viscosin. In the low-lipid regime at cL ≪ 1/K, virtually all CLiP is in solution, 1/K becomes important and the "cation attacks anionic membrane" selectivity gets restored. Overall, activity and selectivity data can only properly be interpreted if the lipid regime is known and predictions for other lipid concentrations or cell counts require knowledge of 1/K and Re50.

Dataset Information

Glucose-Induced Cyclic Lipopeptides Resistance in Bacteria via ATP Maintenance through Enhanced Glycolysis.

Publications

Glucose-Induced Cyclic Lipopeptides Resistance in Bacteria via ATP Maintenance through Enhanced Glycolysis.

Similar Datasets

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