Combined Use of the Ab105-2φΔCI Lytic Mutant Phage and Different Antibiotics in Clinical Isolates of Multi-Resistant Acinetobacter baumannii

Phage therapy is an abandoned antimicrobial therapy that has been resumed in recent years. In this study, we mutated a lysogenic phage from Acinetobacter baumannii into a lytic phage (Ab105-2phiΔCI) that displayed antimicrobial activity against A. baumannii clinical strain Ab177_GEIH-2000 (isolated...

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Detalhes bibliográficos
Autores: Blasco, Lucía, Ambroa, Antón, López, María, Fernández García, Laura, Bleriot, Inés, Trastoy, Rocío, Rodríguez-Baño, Jesús, Pascual Hernández, Álvaro, Cisneros, José Miguel, Pachón Díaz, Jerónimo, Tomás, María
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/172250
Acesso em linha:https://hdl.handle.net/11441/172250
https://doi.org/10.3390/microorganisms7110556
Access Level:acceso abierto
Palavra-chave:acinetobacter baumannii
multiresistant
mutant lytic phage
phage therapy
antibiotic-phage synergy
Descrição
Resumo:Phage therapy is an abandoned antimicrobial therapy that has been resumed in recent years. In this study, we mutated a lysogenic phage from Acinetobacter baumannii into a lytic phage (Ab105-2phiΔCI) that displayed antimicrobial activity against A. baumannii clinical strain Ab177_GEIH-2000 (isolated in the GEIH-REIPI Spanish Multicenter A. baumannii Study II 2000/2010, Umbrella Genbank Bioproject PRJNA422585, and for which meropenem and imipenem MICs of respectively, 32 µg/mL, and 16 µg/mL were obtained). We observed an in vitro synergistic antimicrobial effect (reduction of 4 log–7 log CFU/mL) between meropenem and the lytic phage in all combinations analyzed (Ab105-2phiΔCI mutant at 0.1, 1 and 10 MOI and meropenem at 1/4 and 1/8 MIC). Moreover, bacterial growth was reduced by 8 log CFU/mL for the combination of imipenem at 1/4 MIC plus lytic phage (Ab105-2phiΔCI mutant) and by 4 log CFU/mL for the combination of imipenem at 1/8 MIC plus lytic phage (Ab105-2phiΔCI mutant) at both MOI 1 and 10. These results were confirmed in an in vivo model (G. mellonella), and the combination of imipenem and mutant Ab105-2phiΔCI was most effective (p < 0.05). This approach could help to reduce the emergence of phage resistant bacteria and restore sensitivity to antibiotics used to combat multi-resistant strains of Acinetobacter baumannii.