The insect antimicrobial peptide cecropin A disrupts uropathogenic Escherichia coli biofilms.
Animals
Antimicrobial Cationic Peptides
/ administration & dosage
Biofilms
/ drug effects
Cell Membrane Permeability
/ drug effects
Disease Models, Animal
Drug Synergism
Escherichia coli Infections
/ microbiology
Escherichia coli Proteins
/ genetics
Gene Expression Regulation, Bacterial
/ drug effects
Lepidoptera
Microbial Sensitivity Tests
Microbial Viability
/ drug effects
Mortality
Nalidixic Acid
/ pharmacology
Pore Forming Cytotoxic Proteins
/ administration & dosage
Uropathogenic Escherichia coli
/ drug effects
Journal
NPJ biofilms and microbiomes
ISSN: 2055-5008
Titre abrégé: NPJ Biofilms Microbiomes
Pays: United States
ID NLM: 101666944
Informations de publication
Date de publication:
12 02 2020
12 02 2020
Historique:
received:
12
09
2019
accepted:
15
01
2020
entrez:
14
2
2020
pubmed:
14
2
2020
medline:
23
3
2021
Statut:
epublish
Résumé
Current antibiotics cannot eradicate uropathogenic Escherichia coli (UPEC) biofilms, leading to recurrent urinary tract infections. Here, we show that the insect antimicrobial peptide cecropin A (CecA) can destroy planktonic and sessile biofilm-forming UPEC cells, either alone or when combined with the antibiotic nalidixic acid (NAL), synergistically clearing infection in vivo without off-target cytotoxicity. The multi-target mechanism of action involves outer membrane permeabilization followed by biofilm disruption triggered by the inhibition of efflux pump activity and interactions with extracellular and intracellular nucleic acids. These diverse targets ensure that resistance to the CecA + NAL combination emerges slowly. The antimicrobial mechanisms of CecA, thus, extend beyond pore-forming activity to include an unanticipated biofilm-eradication process, offering an alternative approach to combat antibiotic-resistant UPEC infections.
Identifiants
pubmed: 32051417
doi: 10.1038/s41522-020-0116-3
pii: 10.1038/s41522-020-0116-3
pmc: PMC7016129
doi:
Substances chimiques
Antimicrobial Cationic Peptides
0
Escherichia coli Proteins
0
Pore Forming Cytotoxic Proteins
0
Nalidixic Acid
3B91HWA56M
cecropin A
80451-04-3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6Commentaires et corrections
Type : CommentIn
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