RT Journal Article T1 In vitro and in vivo efficacy of combinations of colistin and different endolysins against clinical strains of multi-drug resistant pathogens A1 Blasco, Lucia A1 Ambroa, Anton A1 Trastoy, Rocio A1 Bleriot, Ines A1 Moscoso, Miriam A1 Fernández-Garcia, Laura A1 Perez-Nadales, Elena A1 Fernández-Cuenca, Felipe A1 Torre-Cisneros, Julian A1 Oteo-Iglesias, Jesus A1 Oliver, Antonio A1 Canton, Rafael A1 Kidd, Tim A1 Navarro, Ferran A1 Miró, Elisenda A1 Pascual, Alvaro A1 Bou, German A1 Martínez-Martínez, Luis A1 Tomas, Maria K1 Anti-infective agents K1 Drug resistance, multiple, bacterial K1 Genome K1 Gram-negative bacteria K1 Colistin K1 Microbial sensitivity tests K1 Antiinfecciosos K1 Farmacorresistencia bacteriana múltiple K1 Genoma K1 Bacterias gramnegativas K1 Colistina K1 Pruebas de sensibilidad microbiana AB The emergence of multidrug resistant (MDR) pathogenic bacteria is jeopardizing the value of antimicrobials, which had previously changed the course of medical science. In this study, we identified endolysins ElyA1 and ElyA2 (GH108-PG3 family), present in the genome of bacteriophages Ab1051Φ and Ab1052Φ, respectively. The muralytic activity of these endolysins against MDR clinical isolates (Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae) was tested using the turbidity reduction assay. Minimal inhibitory concentrations (MICs) of endolysin, colistin and a combination of endolysin and colistin were determined, and the antimicrobial activity of each treatment was confirmed by time kill curves. Endolysin ElyA1 displayed activity against all 25 strains of A. baumannii and P. aeruginosa tested and against 13 out of 17 strains of K. pneumoniae. Endolysin ElyA2 did not display any such activity. The combined antimicrobial activity of colistin and ElyA1 yielded a reduction in the colistin MIC for all strains studied, except K. pneumoniae. These results were confirmed in vivo in G. mellonella survival assays and in murine skin and lung infection models. In conclusion, combining colistin (1/4 MIC) with the new endolysin ElyA1 (350 µg) enhanced the bactericidal activity of colistin in both in vitro and in vivo studies. This will potentially enable reduction of the dose of colistin used in clinical practice. PB Springer Nature YR 2020 FD 2020-04-28 LK http://hdl.handle.net/10668/3789 UL http://hdl.handle.net/10668/3789 LA en NO Blasco L, Ambroa A, Trastoy R, Bleriot I, Moscoso M, Fernández-Garcia L, et al. In vitro and in vivo efficacy of combinations of colistin and different endolysins against clinical strains of multi-drug resistant pathogens. Sci Rep. 2020 Apr 28;10(1):7163 DS RISalud RD Apr 12, 2025