Journal
MICROORGANISMS
Volume 7, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/microorganisms7110556
Keywords
Acinetobacter baumannii; multiresistant; mutant lytic phage; phage therapy; antibiotic-phage synergy
Categories
Funding
- State Plan for R+D+I 2013-2016 (National Plan for Scientific Research, Technological Development and Innovation 2008-2011) [PI16/01163]
- ISCIII-Deputy General Directorate for Evaluation and Promotion of Research-European Regional Development Fund A way of Making Europe
- Instituto de Salud Carlos III FEDER, Spanish Network for the Research in Infectious Diseases (REIPI) [RD16/0016/0001, RD16/0016/0006, RD16/0016/0007, RD16/0016/0008, RD16/0016/0009, RD16/0016/0010]
- Study Group on Mechanisms of Action and Resistance to Antimicrobials, GEMARA (SEIMC)
- SERGAS (ACIS, Axencia de Conecemento en Saude, Xunta de Galicia)
- Deputacion Provincial da Coruna, Xunta de Galicia
- SEIMC grant
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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 (Ab105-2phi Delta CI) 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 mu g/mL, and 16 mu g/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 (Ab105-2phi Delta CI 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 (Ab105-2phi Delta CI mutant) and by 4 log CFU/mL for the combination of imipenem at 1/8 MIC plus lytic phage (Ab105-2phi Delta CI 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 Ab105-2phi Delta CI 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.
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