Characterization of fmtA, a gene that modulates the expression of methicillin resistance in Staphylococcus aureus

FmtA is a factor which affects the methicillin resistance level in methicillin-resistant Staphylococcus aureus, Since FmtA has two of three conserved;ed motifs which are typically found in penicillin-binding proteins (PBPs) and p-lactamases, we investigated the penicillin-binding activity of recombinant FmtA and found no such activity, Immunoblotting analysis revealed that FmtA localizes in the membrane fraction. To investigate the function of FmtA, high-pressure liquid chromatography analysis of cell wall muropeptides was performed with an fmtA-inactivated mutant and its parent. The mutant showed a reduced cross-linking and partially reduced amidation of glutamate residues in the peptidoglycan of the mutant. The transcription of fmtA was dose dependently increased by the addition of p-lactam antibiotics, fosfomycin, and bacitracin, while its transcription was not changed by the addition of vancomycin or tetracycline. These results reveal that Fmt is a membrane-located, non-penicillin-binding protein and that mutation of fmtA affects the cell wall structure, although its precise function is still unknown.