JAC Advance Access originally published online on March 13, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 803-811
© 2003 The British Society for Antimicrobial Chemotherapy
Role of the acetyltransferase AAC(6')-Iz modifying enzyme in aminoglycoside resistance in Stenotrophomonas maltophilia
Department of Microbiology and Immunology, Queen’s University, Kingston, Ontario, Canada K7L 3N6
Received 17 October 2002; returned 6 December 2002; revised 8 January 2003; accepted 11 January 2003
Stenotrophomonas maltophilia is an emerging nosocomial pathogen that displays high-level intrinsic resistance to multiple antibiotics including aminoglycosides. A gene [aac(6')-Iz] encoding an aminoglycoside-modifying enzyme, AAC(6')-Iz acetyltransferase, was recently cloned and sequenced in S. maltophilia, but its importance with respect to aminoglycoside resistance in this organism was not determined. Using a homologous gene replacement approach, mutants carrying unmarked chromosomal deletions of the aac(6')-Iz gene were constructed in wild-type and in vitro-selected aminoglycoside-resistant S. maltophilia. AAC(6')-Iz-deficient mutants derived from both wild-type and aminoglycoside-resistant strains displayed an increase in susceptibility to amikacin, netilmicin, sisomicin and tobramycin (4- to 32-fold decrease in MICs), known substrates for AAC(6')-I enzymes. The cloned aac(6')-Iz gene restored the aminoglycoside resistance of the aac(6')-Iz mutants, and could also confer aminoglycoside resistance upon Escherichia coli. To assess the significance of the aac(6')-Iz gene with respect to the aminoglycoside resistance of clinical strains, its distribution was assessed in 65 clinical isolates from two hospitals. Using PCR, Southern hybridization, RT–PCR and/or nucleotide sequencing, the aac(6')-Iz gene was identified in 57% of the isolates. Susceptibility tests indicated a good correlation between the presence of the aac(6')-Iz gene and the resistance to tobramycin, netilmicin and sisomicin in these strains. These results indicate that the aac(6')-Iz gene is an important contributor to aminoglycoside resistance in clinical strains of S. maltophilia, particularly to tobramycin.
Keywords: aminoglycoside, resistance, Stenotrophomonas maltophilia
* Corresponding author. Tel: +1-613-533-6677; Fax: +1-613-533-6796; E-mail: poolek{at}post.queensu.ca
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