Azithromycin and Doxycycline Attenuation of Acanthamoeba Virulence in a Human Corneal Tissue Model.
J Infect Dis
; 215(8): 1303-1311, 2017 04 15.
Article
en En
| MEDLINE
| ID: mdl-27578848
ABSTRACT
Background:
Amoebic keratitis is a potentially blinding eye infection caused by ubiquitous, free-living, environmental acanthamoebae, which are known to harbor bacterial endosymbionts. A Chlamydia-like endosymbiont has previously enhanced Acanthamoeba virulence in vitro. We investigated the potential effect of Acanthamoeba-endosymbiont coinfection in a human corneal tissue model representing clinical amoebic keratitis infection.Methods:
Environmental and corneal Acanthamoeba isolates from the American Type Culture Collection were screened for endosymbionts by amplifying and sequencing bacterial 16S as well as Chlamydiales-specific DNA. Each Acanthamoeba isolate was used to infect EpiCorneal cells, a 3-dimensional human corneal tissue model. EpiCorneal cells were then treated with azithromycin, doxycycline, or control medium to determine whether antibiotics targeting common classes of bacterial endosymbionts attenuated Acanthamoeba virulence, as indicated by decreased observed cytopathic effect and inflammatory biomarker production.Results:
A novel endosymbiont closely related to Mycobacterium spp. was identified in Acanthamoeba polyphaga 50495. Infection of EpiCorneal cells with Acanthamoeba castellanii 50493 and A. polyphaga 50372 led to increased production of inflammatory cytokines and cytopathic effects visible under microscopy. These increases were attenuated by azithromycin and doxycycline.Conclusions:
Our findings suggest that azithromycin and doxycycline may be effective adjuvants to standard antiacanthamoebal chemotherapy by potentially abrogating virulence-enhancing properties of bacterial endosymbionts.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Acanthamoeba
/
Chlamydiaceae
/
Doxiciclina
/
Azitromicina
/
Córnea
/
Queratitis
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Infect Dis
Año:
2017
Tipo del documento:
Article