Methicillin resistance in Staphylococcus aureus is primarily due to the acquisition of an additional penicillin-binding protein, PBP2' (also known as PBP2a), that confers resistance to virtually all beta-lactam antibiotics. This foreign PBP2' has strict requirements on peptidoglycan precursor formation and composition in order to function optimally. The level of methicillin resistance is governed by genomic factors which are involved in cell wall metabolism and/or are constituents of the cytoplasmic membrane. The formation of the pentaglycine interpeptide bridge of peptidoglycan plays a key function and depends on at least three factors, FemX, FemA and FemB.