Novel arbekacin- and amikacin-modifying enzyme of methicillin-resistant Staphylococcus aureus

An aminoglycoside-modifying enzyme in arbekacin-resistant methicillin-resis tant Staphylococcus aureus (MRSA), exhibiting 4'''-N-acetylation, was exami ned. Although the MRSA strain with AAC(4''') had no AAC(6')-APH(2 ") activi ty, a DNA fragment of the AAC(6')-APH(2 ") gene was amplified by PCR and th e purified N-terminal 30-amino acid sequence of this AAC(4''') was identica l to AAC(6')-APH(2 "). Direct DNA sequencing of this 'silent' AAC(6')-APH(2 ") gene revealed a single point mutation leading to a substitution of Gly for Asp(80), through which the secondary structure is affected. A change in protein conformation could lead to a cleavage and a change of the enzymati c activity. We propose a new aminoglycoside-resistance mediated by AAC(4''' ) is caused by a mutation-modified AAC(6')-APH(2 "). (C) 2000 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.