Systematic design of pulse dosing to eradicate persister bacteria.
PLoS Comput Biol
; 19(1): e1010243, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36649322
ABSTRACT
A small fraction of infectious bacteria use persistence as a strategy to survive exposure to antibiotics. Periodic pulse dosing of antibiotics has long been considered a potentially effective strategy towards eradication of persisters. Recent studies have demonstrated through in vitro experiments that it is indeed feasible to achieve such effectiveness. However, systematic design of periodic pulse dosing regimens to treat persisters is currently lacking. Here we rigorously develop a methodology for the systematic design of optimal periodic pulse dosing strategies for rapid eradication of persisters. A key outcome of the theoretical analysis, on which the proposed methodology is based, is that bactericidal effectiveness of periodic pulse dosing depends mainly on the ratio of durations of the corresponding on and off parts of the pulse. Simple formulas for critical and optimal values of this ratio are derived. The proposed methodology is supported by computer simulations and in vitro experiments.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bactérias
/
Antibacterianos
Idioma:
En
Revista:
PLoS Comput Biol
Assunto da revista:
BIOLOGIA
/
INFORMATICA MEDICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos