A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage.
PLoS Pathog
; 16(12): e1009192, 2020 12.
Article
en En
| MEDLINE
| ID: mdl-33370414
ABSTRACT
Asymptomatic carriage of Salmonella Typhi continues to facilitate the transmission of typhoid fever, resulting in 14 million new infections and 136,000 fatalities each year. Asymptomatic chronic carriage of S. Typhi is facilitated by the formation of biofilms on gallstones that protect the bacteria from environmental insults and immune system clearance. Here, we identified two unique small molecules capable of both inhibiting Salmonella biofilm growth and disrupting pre-formed biofilm structures without affecting bacterial viability. In a mouse model of chronic gallbladder Salmonella carriage, treatment with either compound reduced bacterial burden in the gallbladder by 1-2 logs resulting in bacterial dissemination to peripheral organs that was associated with increased mortality. Co-administration of either compound with ciprofloxacin not only enhanced compound efficacy in the gallbladder by a further 1-1.5 logs for a total of 3-4.5 log reduction, but also prevented bacterial dissemination to peripheral organs. These data suggest a dual-therapy approach targeting both biofilm and planktonic populations can be further developed as a safe and efficient treatment of biofilm-mediated chronic S. Typhi infections.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
3_ND
/
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
2_enfermedades_transmissibles
/
3_neglected_diseases
/
3_zoonosis
/
4_typhoid_paratyphoid_fever_enteric_fever
/
6_digestive_diseases
Asunto principal:
Salmonelosis Animal
/
Salmonella typhi
/
Portador Sano
/
Biopelículas
/
Vesícula Biliar
/
Antibacterianos
Límite:
Animals
Idioma:
En
Revista:
PLoS Pathog
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos