In vitro efficacy of antibiotics commonly used to treat human plague against intracellular Yersinia pestis.
Antimicrob Agents Chemother
; 55(8): 3752-7, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21628541
ABSTRACT
Yersinia pestis initiates infection as a facultative intracellular parasite in host macrophages; however, little is known about the efficacy of antibiotics commonly used to treat human plague against intracellular Y. pestis. Intracellular minimal bactericidal concentrations (MBCs) were determined using a high-throughput broth microdilution assay in which human THP-1 macrophage-like cells were infected with Y. pestis strain KIM6-2053.1+ and exposed to 2-fold serial dilutions of antibiotics for 24 h in 96-well plates. The numbers of CFU, upon which minimal bactericidal concentrations were based, were determined by counting "microcolonies" in wells of 96-well plates following lysis of tissue culture cells to release surviving Y. pestis, replica dilution, and plating in soft tryptic soy broth agar. For THP-1 cells, streptomycin and ciprofloxacin had comparable efficacies for intra- and extracellular Y. pestis, but the MBCs for chloramphenicol, gentamicin, doxycycline, and amoxicillin were two-, three-, four-, and five 2-fold serial dilutions greater, respectively, for intracellular than for extracellular Y. pestis. During the initial stage of plague, intracellular Y. pestis may be less susceptible to antibiotic killing by particular antibiotics recommended for treatment of plague, such as gentamicin or doxycycline, whereas others, such as streptomycin and ciprofloxacin, may have similar efficacies against extracellular or intracellular Y. pestis. This may be of particular importance in the selection of antibiotics for prophylactic treatment in the case of a bioterrorism event.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peste
/
Yersinia pestis
/
Ensaios de Triagem em Larga Escala
/
Antibacterianos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos