A macromolecular approach to eradicate multidrug resistant bacterial infections while mitigating drug resistance onset.
Nat Commun
; 9(1): 917, 2018 03 02.
Article
de En
| MEDLINE
| ID: mdl-29500445
ABSTRACT
Polymyxins remain the last line treatment for multidrug-resistant (MDR) infections. As polymyxins resistance emerges, there is an urgent need to develop effective antimicrobial agents capable of mitigating MDR. Here, we report biodegradable guanidinium-functionalized polycarbonates with a distinctive mechanism that does not induce drug resistance. Unlike conventional antibiotics, repeated use of the polymers does not lead to drug resistance. Transcriptomic analysis of bacteria further supports development of resistance to antibiotics but not to the macromolecules after 30 treatments. Importantly, high in vivo treatment efficacy of the macromolecules is achieved in MDR A. baumannii-, E. coli-, K. pneumoniae-, methicillin-resistant S. aureus-, cecal ligation and puncture-induced polymicrobial peritonitis, and P. aeruginosa lung infection mouse models while remaining non-toxic (e.g., therapeutic index-ED50/LD50 1473 for A. baumannii infection). These biodegradable synthetic macromolecules have been demonstrated to have broad spectrum in vivo antimicrobial activity, and have excellent potential as systemic antimicrobials against MDR infections.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Infections bactériennes
/
Multirésistance bactérienne aux médicaments
/
Structures macromoléculaires
Limites:
Animals
Langue:
En
Journal:
Nat Commun
Sujet du journal:
BIOLOGIA
/
CIENCIA
Année:
2018
Type de document:
Article
Pays d'affiliation:
Singapour