Clearing an ESKAPE Pathogen in a Model Organism; A Polypyridyl Ruthenium(II) Complex Theranostic that Treats a Resistant Acinetobacter baumannii Infection in Galleria mellonella

Abstract

In previous studies we have described the therapeutic action of luminescent dinuclear ruthenium(II) complexes based on the tetrapyridylphenazine, tpphz, bridging ligand on pathogenic strains of Escherichia coli and Enterococcus faecalis. Herein, the antimicrobial activity of the complex against pernicious Gram-negative ESKAPE pathogenic strains of Acinetobacter baumannii (AB12, AB16, AB184 and AB210) and Pseudomonas aeruginosa (PA2017, PA_ 007_ IMP and PA_ 004_ CRCN) are reported. Estimated minimum inhibitory concentrations and minimum bactericidal concentrations for the complexes revealed the complex shows potent activity against all A. baumannii strains, in both glucose defined minimal media and standard nutrient rich Mueller-Hinton-II. Although the activity was lower in P. aureginosa, a moderately high potency was observed and retained in carbapenem-resistant strains. Optical microscopy showed that the compound is rapidly internalized by A. baumannii. As previous reports had revealed the complex exhibited no toxicity in Galleria Mellonella up to concentrations of 80 mg/kg, the ability to clear pathogenic infection within this model was explored. The pathogenic concentrations to the larvae for each bacterium were determined to be≥105 for AB184 and≥103 CFU/mL for PA2017. It was found a single dose of the compound totally cleared a pathogenic A. baumannii infection from all treated G. mellonella within 96 h. Uniquely, in these conditions thanks to the imaging properties of the complex the clearance of the bacteria within the hemolymph of G. mellonella could be directly visualized through both optical and transmission electron microscopy.