Cloning and characterization of an aminoglycoside 6'-N-acetyltransferase gene from Citrobacter freundii which confers an altered resistance profile.
A novel gene encoding a 6'-N-aminoglycoside acetyltransferase, aac(6')-In, has been cloned and sequenced from Citrobacter freundii 13996-19, a clinical isolate from Venezuela. This gene mediates resistance to amikacin, 2'-N-ethylnetilmicin, isepamicin, kanamycin, netilmicin, and tobramycin. The aac(6')-In gene is 573 nucleotides in length and encodes a putative protein of 190 amino acids. AAC(6')-In is most closely related to AAC(6')-Im and AAC(6')-Ie, demonstrating 64.4% and 62.3% similarity, respectively, at the protein level, suggesting these proteins share a common ancestor. The aac(6')-In flanking sequences demonstrated homology to integron- and transposon-related elements which are often found associated with resistance determinants. Hybridization studies performed with an intragenic probe specific for aac(6')-In indicate that this gene is prevalent within Venezuela but has not been observed outside of the country. Furthermore, the aac(6)-In gene was found in 10 different species of gram-negative bacteria.
Wu
H Y
HY
Department of Chemotherapy and Molecular Genetics, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Miller
G H
GH
Blanco
M G
MG
Hare
R S
RS
Shaw
K J
KJ
D000123:Acetyltransferases / Q000235:genetics*; D000595:Amino Acid Sequence; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D016971:Citrobacter freundii / Q000187:drug effects* / Q000235:genetics*; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010957:Plasmids; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000123:Acetyltransferases; C056532:aminoglycoside N(6')-acetyltransferase