eLife, 2021-04, Vol.10
2021
Details
- Autor(en) / Beteiligte
- Titel
- Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane
- Ist Teil von
- eLife, 2021-04, Vol.10
- Ort / Verlag
- England: eLife Science Publications, Ltd
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Colistin is an antibiotic of last resort, but has poor efficacy and resistance is a growing problem. Whilst it is well established that colistin disrupts the bacterial outer membrane (OM) by selectively targeting lipopolysaccharide (LPS), it was unclear how this led to bacterial killing. We discovered that MCR-1 mediated colistin resistance in is due to modified LPS at the cytoplasmic rather than OM. In doing so, we also demonstrated that colistin exerts bactericidal activity by targeting LPS in the cytoplasmic membrane (CM). We then exploited this information to devise a new therapeutic approach. Using the LPS transport inhibitor murepavadin, we were able to cause LPS accumulation in the CM of , which resulted in increased susceptibility to colistin in vitro and improved treatment efficacy in vivo. These findings reveal new insight into the mechanism by which colistin kills bacteria, providing the foundations for novel approaches to enhance therapeutic outcomes.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2050-084XeISSN: 2050-084XDOI: 10.7554/elife.65836Titel-ID: cdi_doaj_primary_oai_doaj_org_article_f64d8e9c4ae644fe8acd8e4ffd54da30
- Format
- –
- Schlagworte
- Amino acids, Animals, Anti-Bacterial Agents - pharmacology, Antibiotics, Bacteria, Bactericidal activity, Cell Membrane - drug effects, Cell Membrane - metabolism, Cell membranes, Colistin, Colistin - pharmacology, Cystic fibrosis, Cytoplasmic membranes, Disease Models, Animal, Drug resistance, Drug resistance in microorganisms, Drug Resistance, Bacterial, Drug Therapy, Combination, E coli, Escherichia coli, Escherichia coli - drug effects, Escherichia coli - genetics, Escherichia coli - metabolism, Escherichia coli Proteins - genetics, Escherichia coli Proteins - metabolism, Female, Gram-negative bacteria, Health aspects, Humans, Lipids, lipopolysaccharide, Lipopolysaccharides, Lipopolysaccharides - metabolism, Membrane Fluidity - drug effects, Mice, Mice, Inbred C57BL, Microbial Viability - drug effects, Microbiology and Infectious Disease, Mitogens, Peptides, Peptides, Cyclic - pharmacology, phospholipids, Polymyxin, Pseudomonas, Pseudomonas aeruginosa - drug effects, Pseudomonas aeruginosa - genetics, Pseudomonas aeruginosa - metabolism, Pseudomonas Infections - drug therapy, Pseudomonas Infections - microbiology, Respiratory agents, Respiratory Tract Infections - drug therapy, Respiratory Tract Infections - microbiology, Scientific equipment and supplies industry