Small Molecule Adjuvants Potentiate Colistin Activity and Attenuate Resistance Development in
anti-evolution drug
colistin
pmrCAB
pmrH
resistance
small molecules
Journal
Infection and drug resistance
ISSN: 1178-6973
Titre abrégé: Infect Drug Resist
Pays: New Zealand
ID NLM: 101550216
Informations de publication
Date de publication:
2020
2020
Historique:
received:
01
05
2020
accepted:
16
06
2020
entrez:
9
8
2020
pubmed:
9
8
2020
medline:
9
8
2020
Statut:
epublish
Résumé
Colistin is one of the last-resort antibiotics to treat multi-drug resistant (MDR) Gram-negative bacterial infections in humans. Further, colistin has been also used to prevent and treat Enterobacteriaceae infections in food animals. However, chromosomal mutations and mobile colistin resistance ( Investigate the adjuvant potential of novel small molecules (SMs) on colistin. Previously, we identified 11 membrane-affecting SMs with bactericidal activity against avian pathogenic The SM combination synergistically reduced the minimum bactericidal concentration of colistin by at least 10-fold. In larvae, the SM combination increased the efficacy of colistin by two-fold with enhanced (>50%) survival and reduced (>4 logs) APEC load. Further, the SM combination decreased the frequency (5/6 to 1/6) of colistin resistance evolution and downregulated the Our study identified two SMs (SM2 and SM3) that potentiated the colistin activity and attenuated the development of colistin resistance in APEC. These SMs can be developed as anti-evolution drugs that can slow down colistin resistance development.
Sections du résumé
BACKGROUND
BACKGROUND
Colistin is one of the last-resort antibiotics to treat multi-drug resistant (MDR) Gram-negative bacterial infections in humans. Further, colistin has been also used to prevent and treat Enterobacteriaceae infections in food animals. However, chromosomal mutations and mobile colistin resistance (
OBJECTIVE
OBJECTIVE
Investigate the adjuvant potential of novel small molecules (SMs) on colistin.
MATERIALS AND METHODS
METHODS
Previously, we identified 11 membrane-affecting SMs with bactericidal activity against avian pathogenic
RESULTS
RESULTS
The SM combination synergistically reduced the minimum bactericidal concentration of colistin by at least 10-fold. In larvae, the SM combination increased the efficacy of colistin by two-fold with enhanced (>50%) survival and reduced (>4 logs) APEC load. Further, the SM combination decreased the frequency (5/6 to 1/6) of colistin resistance evolution and downregulated the
CONCLUSION
CONCLUSIONS
Our study identified two SMs (SM2 and SM3) that potentiated the colistin activity and attenuated the development of colistin resistance in APEC. These SMs can be developed as anti-evolution drugs that can slow down colistin resistance development.
Identifiants
pubmed: 32764996
doi: 10.2147/IDR.S260766
pii: 260766
pmc: PMC7360418
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2205-2222Informations de copyright
© 2020 Kathayat et al.
Déclaration de conflit d'intérêts
The authors declare that they have no conflicts of interest.
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