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Nat Commun ; 15(1): 2993, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582763

RESUMO

Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus. We also characterize immune responses elicited following administration of the phage cocktail. While minimal innate responses are observed after phage administration, two rounds of treatment induces phage-specific neutralizing antibodies and accelerate phage clearance from tissues. Interestingly, the myophages in our cocktail induce a more robust neutralizing antibody response than the siphophages. This anti-phage immunity reduces the effectiveness of the phage cocktail in our murine model. Collectively, this study shows phage-specific immune responses may be an important consideration in the development of phage cocktails for therapeutic use.


Assuntos
Bacteriófagos , Enterococos Resistentes à Vancomicina , Humanos , Animais , Camundongos , Bacteriófagos/fisiologia , Vancomicina/farmacologia , Modelos Animais de Doenças , Myoviridae/fisiologia , Antibacterianos/farmacologia
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