Expanding the physiological roles of Multiple Peptide Resistance Factor: MprF function in Bacillus subtilis
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Publisher:The Ohio State University Thesis
Series/Report no.:The Ohio State University. College of Biological Sciences Honors Theses; 2010
Multiple peptide resistance factor (MprF) is a membrane bound protein that adds lysine to phosphatidylglycerol (PG) using an elongator Lys-tRNALys. This lipid modification changes the net charge of the cell wall which results in cellular permeability changes that confer resistance to cationic antibiotics. Point mutations in mprF have been shown to cause spontaneous resistance to daptomycin, a last resort antibiotic in the treatment of the pathogen Methicillin resistant Staphylococcus aureus (MRSA) that is believed to have CAMP-like properties and mode of action . Due to the effects of altering membrane permeability and increased antibiotic resistance, mprF constitutes as a virulence factor in MRSA. Cell wall modifications by MprF have been shown to have broader effects in other bacteria such as the Gram-negative Pseudomonas aeruginosa where it confers resistance to acidic conditions, chromium, cefsulodin, and protamine. In this work expanded roles of mprF in the Gram-positive microorganism Bacillus subtilis were elucidated through Biolog Phenotype MicroArrays, the technology of which allows for the performance of high-throughput screens of 2,000 physiological phenotypes. Presented here is data based on the comparison of wild type B. subtilis 1A100 growth to that of a marker-less deletion strain of mprF. This data shows a decreased ability of the deletion strain to survive in the presence of several antibiotics, cationic molecules and lipophilic compounds indicating a global effect of mprF on cell wall permeability in B. subtilis. These effects, while consistent with previous data from L. monocytogenes, indicate that MprF plays similar, yet varied, roles in diverse microorganisms through modification of cell wall properties. The discovery of such a widespread mechanism among bacterial species has important implications for the development of an MprF inhibitor that has broad range specificity to a multitude of pathogens.