Mar 26, 2003

Role of the acetyltransferase AAC(6')-Iz modifying enzyme in aminoglycoside resistance in Stenotrophomonas maltophilia

The Journal of Antimicrobial Chemotherapy
Xian-Zhi LiKeith Poole

Abstract

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, Southe...Continue Reading

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Mentioned in this Paper

Aminoglycoside [EPC]
Alkalescens-Dispar Group
Enzymes, antithrombotic
Aminoglycosides
Antibiotic throat preparations
Pathogenic Organism
Southern Hybridization
Antifungal Antibiotics, Topical
Sisomicin
Reverse Transcriptase Polymerase Chain Reaction

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