Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane.
Animals
Anti-Bacterial Agents
/ pharmacology
Cell Membrane
/ drug effects
Colistin
/ pharmacology
Disease Models, Animal
Drug Resistance, Bacterial
Drug Therapy, Combination
Escherichia coli
/ drug effects
Escherichia coli Proteins
/ genetics
Female
Humans
Lipopolysaccharides
/ metabolism
Membrane Fluidity
/ drug effects
Mice, Inbred C57BL
Microbial Viability
/ drug effects
Peptides, Cyclic
/ pharmacology
Pseudomonas Infections
/ drug therapy
Pseudomonas aeruginosa
/ drug effects
Respiratory Tract Infections
/ drug therapy
Colistin
E. coli
Polymyxin
Pseudomonas
infectious disease
lipopolysaccharide
microbiology
phospholipids
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
06 04 2021
06 04 2021
Historique:
received:
16
12
2020
accepted:
31
03
2021
pubmed:
7
4
2021
medline:
27
10
2021
entrez:
6
4
2021
Statut:
epublish
Résumé
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 Antibiotics are life-saving medicines, but many bacteria now have the ability to resist their effects. For some infections, all frontline antibiotics are now ineffective. To treat infections caused by these highly resistant bacteria, clinicians must use so-called ‘antibiotics of last resort’. These antibiotics include a drug called colistin, which is moderately effective, but often fails to eradicate the infection. One of the challenges to making colistin more effective is that its mechanism is poorly understood. Bacteria have two layers of protection against the outside world: an outer cell membrane and an inner cell membrane. To kill them, colistin must punch holes in both. First, it disrupts the outer membrane by interacting with molecules called lipopolysaccharides. But how it disrupts the inner membrane was unclear. Bacteria have evolved several different mechanisms that make them resistant to the effects of colistin. Sabnis et al. reasoned that understanding how these mechanisms protected bacteria could reveal how the antibiotic works to damage the inner cell membrane. Sabnis et al. examined the effects of colistin on
Autres résumés
Type: plain-language-summary
(eng)
Antibiotics are life-saving medicines, but many bacteria now have the ability to resist their effects. For some infections, all frontline antibiotics are now ineffective. To treat infections caused by these highly resistant bacteria, clinicians must use so-called ‘antibiotics of last resort’. These antibiotics include a drug called colistin, which is moderately effective, but often fails to eradicate the infection. One of the challenges to making colistin more effective is that its mechanism is poorly understood. Bacteria have two layers of protection against the outside world: an outer cell membrane and an inner cell membrane. To kill them, colistin must punch holes in both. First, it disrupts the outer membrane by interacting with molecules called lipopolysaccharides. But how it disrupts the inner membrane was unclear. Bacteria have evolved several different mechanisms that make them resistant to the effects of colistin. Sabnis et al. reasoned that understanding how these mechanisms protected bacteria could reveal how the antibiotic works to damage the inner cell membrane. Sabnis et al. examined the effects of colistin on
Identifiants
pubmed: 33821795
doi: 10.7554/eLife.65836
pii: 65836
pmc: PMC8096433
doi:
pii:
Substances chimiques
Anti-Bacterial Agents
0
Escherichia coli Proteins
0
Lipopolysaccharides
0
MCR-1 protein, E coli
0
Peptides, Cyclic
0
murepavadin
0D02GRY87Z
Colistin
Z67X93HJG1
Banques de données
Dryad
['10.5061/dryad.98sf7m0hh']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MR/N014103/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107660/Z/15Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204337/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P028225/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 105603/Z/14/Z
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009505/1
Pays : United Kingdom
Informations de copyright
© 2021, Sabnis et al.
Déclaration de conflit d'intérêts
AS, KH, AK, MB, LE, RF, DM, RM, MS, JD, GL, TC, AE No competing interests declared
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