In vitro and in vivo efficacy of combinations of colistin and different endolysins against clinical strains of multi-drug resistant pathogens

Lucia Blasco, Anton Ambroa, Rocio Trastoy, Ines Bleriot, Miriam Moscoso, Laura Fernández-Garcia, Elena Perez-Nadales, Felipe Fernández-Cuenca, Julian Torre-Cisneros, Jesus Oteo-Iglesias, Antonio Oliver, Rafael Canton, Tim Kidd, Ferran Navarro, Elisenda Miró, Alvaro Pascual, German Bou, Luis Martínez-Martínez, Maria Tomas*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number7163
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

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