MBE Advance Access published online on April 2, 2003
Molecular Biology and Evolution, doi:10.1093/molbev/msg074
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2003; all rights reserved
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1 Biology Dept., University of Rochester
* To whom correspondence should be addressed. E-mail: drbh{at}mail.rochester.edu.
The AAC(6') enzymes inactivate aminoglycoside antibiotics by acetylating their substrates at the 6' position. Based on functional similarity and size similarity the AAC(6') enzymes have been considered to be members of a single family. Our phylogenetic analysis shows that the AAC(6') enzymes instead belong to three unrelated families that we now designate as [A], [B], and [C] and there that aminoglycoside acetylation at the 6' position has evolved independently at least three times. AAC(6')-Iaa is a typical member of the [A] family in that it acetylates tobramycin, kanamycin and amikacin effectively, but acetylates gentamicin ineffectively. The potential of aac(6')-Iaa to increase resistance to tobramycin, kanamycin or amikacin or to acquire resistance to gentamicin was assessed by in vitro evolution. Libraries of PCR mutagenized alleles were screened for increased resistance to tobramycin, kanamycin, and amikacin, but no isolates that conferred more resistance than the wild-type gene were recovered. The library sizes were sufficient to conclude with 97% confidence that no single base substitution mutation or combination of two base substitution mutations in aac(6')-Iaa is capable of increasing resistance to the antibiotics used. It is therefore very unlikely that aac(6')-Iaa of S. typhimurium LT2 has the potential to evolve increased aminoglycoside resistance in nature.
© 2003 Society for Molecular Biology and Evolution
Original Articles
Determining the Limits of the Evolutionary Potential of an Antibiotic Resistance Gene
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