Methicillin-resistant staphylococcus aureus (MRSA) is a serious pathogen that can cause patient mortality and extend hospital stays, resulting in higher health care costs. Currently, over 50% of staph cases around the world are caused by MRSA. In recent years, MRSA has evolved into several resistant strains that can resist to multiple antibiotics such as penicillin, vancomycin, tetracycline and erythromycin. For this reason, they are sometimes called superbugs. In recent years, these superbugs have become a serious threat to public health. Because of the increasing presence of MRSA-related infections, especially in hospitals, there are urgent needs for effective and novel antibiotic therapies. In a preliminary study, we have isolated a novel compound, kaempferol 3-O-alpha-L-(2,3-di-p-coumaroyl)rhamnoside (KCR) from the American sycamore (Platanus occidentalis) that were active against MRSA and VRSA (vancomycin resistant staphylococcus aureus) in vitro and in vivo. The sycamore materials have been classified by the USDA as generally regarded as safe (GRAS) because of extensive human contact and use of this plant in traditional folk medicines and paper industry, among others. Active metabolites of these anti-MRSA compounds likely possess a distinct mechanism of action as they do not show cross resistance or structural homology with established antibiotics. In this proposal, we plan to furthe investigate these highly selective anti-MRSA KCR (platanosides) including the maximum tolerated dose (MTD), therapeutic efficacy, pharmacokinetics (PK), mechanism of action, and in vivo toxicity using animal model and microbiological techniques. This project clearly has the potential to generate a first in class new antibiotic with a novel mechanism of action and provides a unique opportunity for US economic development. In addition, the success of this project will address the limitations of current therapies for the control of MRSA and other antibiotic-resistant staph infections such as VRSA.
MRSA stands for methicillin-resistant staphylococcus aureus, which is a serious drug-resistant pathogen that causes patient mortality, extend hospital stays and higher health care costs. Statistical data suggest that as many as 19,000 people per year have died from MRSA in the U.S. In recent years, MRSA has evolved into several resistant strains that can resist to multiple antibiotics such as penicillin, vancomycin, tetracycline and erythromycin. For this reason, they are sometimes called 'superbugs.' In recent years, these 'superbugs' have become a serious threat to public health. Because of the increasing presence of MRSA-related infections, there are urgent needs for effective and novel antibiotic therapies. In this project, we plan to investigate novel leaf compound known as KCR from American sycamore that exhibit potent anti-MRSA activity in a preliminary study. We propose to further study the therapeutic effects and the biological properties of the extracts using animal model and modern microbiological techniques. The success of this project will generate a first in class new antibiotic for treating drug-resistant infections. This project also will provide a unique opportunity for US economic development.
