Pizarro-Guajardo M1Díaz-González F1Álvarez-Lobos M2Paredes-Sabja D1Front Cell Infect Microbiol. 2017 Aug 14;7:365. doi: 10.3389/fcimb.2017.00365. eCollection 2017.

1
Microbiota-Host Interactions and Clostridia Research Group, Departamento de Ciencias Biologicas, Universidad Andres BelloSantiago, Chile.
2
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad CatólicaSantiago, Chile.

Abstract

Clostridium difficile infection (CDI) are the leading cause of world-wide nosocomial acquired diarrhea. The current main clinical challenge in CDI is the elevated rate of infection recurrence that may reach up to 30% of the patients, which has been associated to the formation of dormant spores during the infection. We sought to characterize the effects of oral administration of specific anti-spore IgY in mouse models of CDI and recurrent CDI. The specificity of anti-spore IgY was evaluated in vitro. In both, initiation mouse model and recurrence mouse model, we evaluated the prophylactic and therapeutic effect of anti-spore IgY, respectively. Our results demonstrate that anti-spore IgY exhibited high specificity and titers against C. difficile spores and reduced spore adherence to intestinal cells in vitro. Administration of anti-spore IgY to C57BL/6 mice prior and during CDI delayed the appearance of the diarrhea by 1.5 day, and spore adherence to the colonic mucosa by 90%. Notably, in the recurrence model, co-administration of anti-spore IgY coupled with vancomycin delayed the appearance of recurrent diarrhea by a median of 2 days. Collectively, these observations suggest that anti-spore IgY antibodies may be used as a novel prophylactic treatment for CDI, or in combination with antibiotics to treat CDI and prevent recurrence of the infection.

KEYWORDS:

Clostridium difficile spores; chicken immunoglobulin IgY; exosporium; germination; immunotherapy; passive immunization; recurrent CDI; sporulation

PMID:
 
28856119
 
PMCID:
 
PMC5557795
 
DOI:
 
10.3389/fcimb.2017.00365