RT Journal Article
T1 Development of an Anti-Acinetobacter baumannii Biofilm Phage Cocktail: Genomic Adaptation to the Host.
A1 Blasco, L
A1 Bleriot, I
A1 Gonzalez de Aledo, M
A1 Fernandez-Garcia, L
A1 Pacios, O
A1 Oliveira, H
A1 Lopez, M
A1 Ortiz-Cartagena, C
A1 Fernandez-Cuenca, F
A1 Pascual, A
A1 Martinez-Martinez, L
A1 Pachon, J
A1 Azeredo, J
A1 Tomas, M
K1 Acinetobacter
K1 Acinetobacter baumannii
K1 Adaptation
K1 Anti-biofilm.
K1 Bacteriophages
K1 Baumannii
K1 Biofilms
K1 Cocktail
K1 Phages
AB The need for alternatives to antibiotic therapy due to the emergence of multidrug resistant bacteria (MDR), such as the nosocomial pathogen Acinetobacter baumannii, has led to the recovery of phage therapy. In addition, phages can be combined in cocktails to increase the host range. In this study, the evolutionary mechanism of adaptation was utilized in order to develop a phage adapted to A. baumannii, named phage Ab105-2phiΔCI404ad, from a mutant lytic phage, Ab105-2phiΔCI, previously developed by our group. The whole genome sequence of phage Ab105-2phiΔCI404ad was determined, showing that four genomic rearrangements events occurred in the tail morphogenesis module affecting the ORFs encoding the host receptor binding sites. As a consequence of the genomic rearrangements, 10 ORFs were lost and four new ORFs were obtained, all encoding tail proteins; two inverted regions were also derived from these events. The adaptation process increased the host range of the adapted phage by almost 3-fold. In addition, a depolymerase-expressing phenotype, indicated by formation of a halo, which was not observed in the ancestral phage, was obtained in 81% of the infected strains. A phage cocktail was formed by combining this phage with the A. baumannii phage vB_AbaP_B3, known to express a depolymerase. Both the individual phages and the phage cocktail showed strong antimicrobial activity against 5 clinical strains and 1 reference strain of A. baumannii tested. However, in all cases resistance to the bacterial strains was also observed. The antibiofilm activity of the individual phages and the cocktail was assayed. The phage cocktail displayed strong antibiofilm activity.
PB American Society for Microbiology
YR 2022
FD 2022-01-12
LK http://hdl.handle.net/10668/20032
UL http://hdl.handle.net/10668/20032
LA en
NO Blasco L, Bleriot I, González de Aledo M, Fernández-García L, Pacios O, Oliveira H, et al. Development of an Anti-Acinetobacter baumannii Biofilm Phage Cocktail: Genomic Adaptation to the Host. Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0192321
NO This study was funded by grants PI16/01163 and PI19/00878 awarded to M.T. within theState Plan for R1D1I 2013-2016 (National Plan for Scientific Research, TechnologicalDevelopment and Innovation 2008-2011) and cofinanced by the ISCIII-Deputy GeneralDirectorate for Evaluation and Promotion of Research—European Regional DevelopmentFund “A Way of Making Europe” and Instituto de Salud Carlos III FEDER, Spanish Networkfor the Research in Infectious Diseases (REIPI, RD16/0016/0001, RD16/0016/0006, andRD16/CIII/0004/0002) and by the Study Group on Mechanisms of Action and Resistance toAntimicrobials, GEMARA (SEIMC, http://www.seimc.org/). M.T. was financially supported bythe Miguel Servet Research Program (SERGAS and ISCIII). I.B. was financially supported bythe pFIS program (ISCIII, FI20/00302). O.P. and M.L. were financially supported by grantsIN606A-2020/035 and IN606B-2018/008, respectively (GAIN, Xunta de Galicia).
DS RISalud
RD Apr 7, 2025