Abstract
An aminoglycoside-modifying enzyme in arbekacin-resistant methicillin-resistant Staphylococcus aureus (MRSA), exhibiting 4'''-N-acetylation, was examined. Although the MRSA strain with AAC(4''') had no AAC(6')-APH(2") activity, a DNA fragment of the AAC(6')-APH(2") gene was amplified by PCR and the purified N-terminal 30-amino acid sequence of this AAC(4''') was identical 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 Asp80, through which the secondary structure is affected. A change in protein conformation could lead to a cleavage and a change of the enzymatic activity. We propose a new aminoglycoside-resistance mediated by AAC(4''') is caused by a mutation-modified AAC(6')-APH(2").
MeSH terms
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Acetyltransferases / chemistry
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Acetyltransferases / genetics
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Acetyltransferases / metabolism*
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Amikacin / pharmacology*
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Aminoglycosides*
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Anti-Bacterial Agents / pharmacology*
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Dibekacin / analogs & derivatives
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Dibekacin / pharmacology*
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Drug Resistance, Microbial
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Humans
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Methicillin Resistance
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Microbial Sensitivity Tests
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Mutation
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Phosphotransferases (Alcohol Group Acceptor) / chemistry
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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Polymerase Chain Reaction
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Sequence Analysis, DNA
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Staphylococcal Infections / microbiology
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Staphylococcus aureus / drug effects*
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Staphylococcus aureus / enzymology*
Substances
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Aminoglycosides
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Anti-Bacterial Agents
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Dibekacin
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Amikacin
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6'-aminoglycoside acetyltransferase-2''-aminoglycoside phosphotransferase
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Acetyltransferases
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aminoglycoside acetyltransferase
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Phosphotransferases (Alcohol Group Acceptor)
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arbekacin