Abstract
Purpose :
This study tested a non-ocular multi-drug resistant isolate of Pseudomonas aeruginosa (MDR9) for susceptibility to glycyrrhizin (GLY) and whether GLY potentiates the effects of ciprofloxacin to which MDR9 is resistant.
Methods :
Antibiotic sensitivity was confirmed using a HARDYISKTM sensitivity test. MIC for GLY and ciprofloxacin combinations and in vitro assays testing GLY effects on: bacterial membrane permeability, efflux pump expression, biofilm formation and adhesion to mouse and human corneal epithelial cells were done. C57BL/6 mice were infected with MDR9 and treated with GLY alone at 6 and at 18 h p.i. with GLY plus ciprofloxacin. Clinical score, photography (slit lamp), myeloperoxidase (MPO) assay, plate count, and RT-PCR were performed.
Results :
MIC for GLY was 40mg/ml and 32μg/ml for ciprofloxacin; MIC for ciprofloxacin was reduced 2 fold when combined with ½ MIC GLY. GLY enhanced bacterial membrane permeability and reduced efflux pump expression, biofilm formation and cell adherence. In vivo, GLY was nontoxic and effective at reducing plate count, PMN infiltrate and proinflammatory molecules when treatment began at 6h p.i. When delaying treatment to 18 h p.i. ciprofloxacin +GLY best reduced clinical scores, the PMN infiltrate and bacterial load compared to ciprofloxacin or GLY alone.
Conclusions :
GLY regulates several multi-drug resistant virulence factors (membrane permeability, efflux pumps, adherence, biofilm) and is therapeutic by reducing inflammation, PMN number and bacterial load. Most significantly, GLY bioenhances the effects of ciprofloxacin to which MDR9 is resistant and shows clinical relevancy as an adjunct therapy to treat multi-drug resistant Pseudomonas aeruginosa corneal infections.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.