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Effects of alterations of the E. coli lipopolysaccharide layer on membrane permeabilization events induced by Cecropin A
| Content Provider | Scilit |
|---|---|
| Author | Agrawal, Anurag Weisshaar, James C. |
| Copyright Year | 2018 |
| Description | Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes The outermost layer of Gram negative bacteria is composed of a lipopolysaccharide (LPS) network that forms a dense protective hydrophilic barrier against entry of hydrophobic drugs. At low μM concentrations, a large family of cationic polypeptides known as antimicrobial peptides (AMPs) are able to penetrate the LPS layer and permeabilize the outer membrane (OM) and the cytoplasmic membrane (CM), causing cell death. Cecropin A is a well-studied cationic AMP from moth. Here a battery of time-resolved, single-cell microscopy experiments explores how deletion of sugar layers and/or phosphoryl negative charges from the core oligosaccharide layer (core OS) of K12 E. coli alters the timing of OM and CM permeabilization induced by Cecropin A. Deletion of sugar layers, or phosphoryl charges, or both from the core OS shortens the time to the onset of OM permeabilization to periplasmic GFP and also the lag time between OM permeabilization and CM permeabilization. Meanwhile, the 12-h minimum inhibitory concentration (MIC) changes only twofold with core OS alterations. The results suggest a two-step model in which the core oligosaccharide layers act as a kinetic barrier to penetration of Cecropin A to the lipid A outer leaflet of the OM. Once a threshold concentration has built up at the lipid A leaflet, nucleation occurs and the OM is locally permeabilized to GFP and, by inference, to Cecropin A. Whenever Cecropin A permeabilizes the OM, CM permeabilization always follows, and cell growth subsequently halts and never recovers on the 45 min observation timescale. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5957292/pdf |
| Ending Page | 1479 |
| Page Count | 10 |
| Starting Page | 1470 |
| ISSN | 00052736 |
| DOI | 10.1016/j.bbamem.2018.04.009 |
| Journal | Biochimica et Biophysica Acta (BBA) - Biomembranes |
| Issue Number | 7 |
| Volume Number | 1860 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2018-07-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes Biochemistry and Molecular Biology Antimicrobial Peptides Cecropin A Core Oligosaccharide Mutations Deep Rough Mutants Lipopolysaccharide Layer Single-cell Timing Measurements |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Biophysics |
