Blasco, LuciaAmbroa, AntonTrastoy, RocioBleriot, InesMoscoso, MiriamFernández-Garcia, LauraPerez-Nadales, ElenaFernández-Cuenca, FelipeTorre-Cisneros, JulianOteo-Iglesias, JesusOliver, AntonioCanton, RafaelKidd, TimNavarro, FerranMiró, ElisendaPascual, AlvaroBou, GermanMartínez-Martínez, LuisTomas, Maria2022-07-132022-07-132020-04-28Blasco 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):7163http://hdl.handle.net/10668/3789The 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Anti-infective agentsDrug resistance, multiple, bacterialGenomeGram-negative bacteriaColistinMicrobial sensitivity testsAntiinfecciososFarmacorresistencia bacteriana múltipleGenomaBacterias gramnegativasColistinaPruebas de sensibilidad microbianaMedical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Macrocyclic Compounds::Peptides, Cyclic::Polymyxins::ColistinMedical Subject Headings::Phenomena and Processes::Microbiological Phenomena::Drug Resistance, Microbial::Drug Resistance, Bacterial::Drug Resistance, Multiple, BacterialMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::EndopeptidasesMedical Subject Headings::Organisms::Bacteria::Gram-Negative BacteriaMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Microbiological Techniques::Microbial Sensitivity TestsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective AgentsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::GenomeMedical Subject Headings::Organisms::Viruses::BacteriophagesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animalsresearch article32346029open access10.1038/s41598-020-64145-72045-2322PMC7188820