Singapore Eye Research Institute Singapore
Title: Breaking down barriers to promote effective antibiotic action
Roger W Beuerman is currently Senior Scientific Director of the Singapore Eye Research Institute, Professor of Neuroscience and Behavioral Disorders at DUKE-NUS School of Medicine and Adjunct Professor of Ophthalmology, Yong Loo Lin, School of Medicine at the National University of Singapore, and Head of Translational Research, and National Distinguished Professor (FidiPro) of Ophthalmology at the University of Tampere Medical School in Finland. His focus has been on understanding eye disease for the development of new diagnostics and therapeutics for infectious disease.
Gram negative bacteria are a particular therapeutic issue as they mutate readily, and this tendency is especially common for Pseudomonas aeruginosa resulting in clinically resistant strains. To combat this problem some antibiotics are used at much higher concentrations to combat Pseudomonas. Part of the issue of admitting antibiotics into these bacteria and killing gram negative bacteria lies in the protective outer membrane, which is overlain with lipopolysaccharide, LPS. Small, branched peptides that interact with various sites in the LPS assembly with the results that the LPS change its structural mode is being developed. It is hypothesized that this may allow greater penetration of antibiotics into the bacteria. To test this idea, the method of fractional inhibitory concentration index was used to test gatifloxicin and a peptide B2099. It was found that the FICI was about 0.53 suggesting that there was synergistic action between the peptide and the gatifloxicin. Next, this combination was tested in a mouse model of corneal infection using P. aeruginosa ATCC9027 with B2099 (0.5 mg/ml), gatifloxicin (3 mg/ml-the standard ophthalmic dose), and a combination of B2099 (0.5 mg/ml) and gatifloxicin (1.5 mg/ml-half the usual dose). The result showed that the combination was significantly more active than either drug alone. Further, it was shown that B2099 interacts with lipid A to allow penetration of the gatifloxicin and the effect extends to E. coli and K. pneumonia. This unique interaction may provide a new method for killing this difficult group of pathogens.
Speaker PPTsDownload PPT