Proposal for a Rational Nomenclature for Phenotype, Genotype and Aminoglycoside-Aminocyclitol Modifying Enzymes

Mitsuhashi, Susumu

doi:10.1007/978-3-642-66062-7_15

Cited by 19 publications

(16 citation statements)

References 43 publications

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“…1. For E. coli containing pSCH4663 [aac(6')-Ib gene], the MIC of amikacin was 16 ,ug/ml, that of tobramycin was 8 p,g/ml, and that of 2'-N-ethylnetilmicin was 32 ,ug/ml, indicating that the AAC(6')-Ib enzyme was capable of acetylating these aminoglycosides. The AAC(6')-Ib enzyme was unable to acetylate 6'-N-ethylnetilmicin because of the ethyl substitution at the B.…”

Section: Resultsmentioning

confidence: 99%

Genetic analysis of bacterial acetyltransferases: identification of amino acids determining the specificities of the aminoglycoside 6'-N-acetyltransferase Ib and IIa proteins

Rather¹,

Munayyer²,

Mann³

et al. 1992

J Bacteriol

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The aminoglycoside 6'-N-acetyltransferase [AAC(6')-I] and AAC(6')-II enzymes represent a class of bacterial proteins capable of acetylating tobramycin, netilmicin, and 2'-N-ethylnetilmicin. However, an important difference exists in their abilities to modify amikacin and gentamicin. The AAC(6')-I enzymes are capable of modifying amikacin. In contrast, the AAC(6')-II enzymes are capable of modifying gentamicin. Nucleotide sequence comparison of the aac(6')-Ib gene and the aac(6')-IIa gene showed 74% sequence identity (K. J. Shaw, C. A. Cramer, M. Rizzo, R. Mierzwa, K. Gewain, G. H. Miller, and R. S. Hare, Antimicrob. Agents Chemother. 33:2052-2062, 1989). Comparison of the deduced protein sequences showed 76% identity and 82% amino acid similarity. A genetic analysis of these two proteins was initiated to determine which amino acids were responsible for the differences in specificity. Results of domain exchanges, which created hybrid AAC(6') proteins, indicated that amino acids in the carboxy half of the proteins were largely responsible for determining specificity. Mutations shifting the specificity of the AAC(6')-Ib protein to that of the AAC(6')-IIa protein (i.e., gentamicin resistance and amikacin sensitivity) have been isolated. DNA sequence analysis of four independent isolates revealed base changes causing the same amino acid substitution, a leucine to serine, at position 119. Interestingly, this serine occurs naturally at the same position in the AAC(6')-IIa protein. Oligonucleotide-directed mutagenesis was used to construct the corresponding amino acid change, a serine to leucine, in the AAC(6')-IIa protein. This change resulted in the conversion of the AAC(6')-IIa substrate specificity to that of AAC(6')-Ib. Analysis of additional amino acid substitutions within this region of AAC(6')-Ib support the model that we have identified an aminoglycoside binding domain of these proteins.

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Section: Resultsmentioning

confidence: 99%

Genetic analysis of bacterial acetyltransferases: identification of amino acids determining the specificities of the aminoglycoside 6'-N-acetyltransferase Ib and IIa proteins

Rather¹,

Munayyer²,

Mann³

et al. 1992

J Bacteriol

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“…Resistance to streptomycin is mediated by several different aminoglycoside-modifying enzymes: ANT(3"), ANT(6), APH(3") and APH(6) (10,18,20). Only ANT(3") is characterized by resistance to streptomycin and spectinomycin (10,18).…”

Section: Resultsmentioning

confidence: 99%

“…The APH(3') AGRPs are characterized by resistance to kanamycin and neomycin (8,10,18,30). At least seven unique APH(3') genes, only some of which are distinguishable by extended resistance profiles to butirosin, lividomycin, amikacin, and gentamicin B (7, 11), have been genetically defined.…”

Section: Resultsmentioning

confidence: 99%

Correlation between aminoglycoside resistance profiles and DNA hybridization of clinical isolates

Shaw¹,

Hare²,

Sabatelli³

et al. 1991

Antimicrob Agents Chemother

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DNA hybridization data and aminoglycoside resistance profiles (AGRPs) were determined for 4,088 clinical isolates from three studies (United States, Belgium, and Argentina). The correlation between susceptibility profiles and hybridization results was determined with nine DNA probes. For each of the seven aminoglycoside resistance profiles which we were able to test, the data suggested at least two distinct genes could encode enzymes which lead to identical resistance profiles. Furthermore, the DNA hybridization data showed that individual strains carried up to six unique aminoglycoside resistance genes. DNA hybridization revealed interesting differences in the frequencies of these genes by organism and by country.

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“…This report describes an analogous spectrophotometric assay, based on kanamycin acetyltransferase [designated AAC(6')-4 by the plasmid group nomenclature (6)]. Because of the broad substrate specificity of these two enzymes (1,12), blood serum levels of all the clinically important aminoglycosides may be readily deternined by using these spectrophotometric methods.…”

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confidence: 99%

Spectrophotometric Assay for Amikacin Using Purified Kanamycin Acetyltransferase

Scarbrough

Williams

Northrop

1979

Antimicrob Agents Chemother

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A rapid spectrophotometric assay has been developed for measuring the concentrations of amikacin and related antibiotics in serum. The assay uses a purified enzyme from R-factor E. coli which acetylates amikacin with the production of coenzyme A, the latter in turn being reacted with a sulfhydryl reagent to produce stoichiometric amounts of a sensitive chromophore, that is measured in the visible spectrum. The system complements an earlier assay for gentamicin-related antibiotics thereby facilitating the rapid measurement of the concentrations of all clinically important aminoglycosides in serum.

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Proposal for a Rational Nomenclature for Phenotype, Genotype and Aminoglycoside-Aminocyclitol Modifying Enzymes

Cited by 19 publications

References 43 publications

Genetic analysis of bacterial acetyltransferases: identification of amino acids determining the specificities of the aminoglycoside 6'-N-acetyltransferase Ib and IIa proteins

Genetic analysis of bacterial acetyltransferases: identification of amino acids determining the specificities of the aminoglycoside 6'-N-acetyltransferase Ib and IIa proteins

Correlation between aminoglycoside resistance profiles and DNA hybridization of clinical isolates

Spectrophotometric Assay for Amikacin Using Purified Kanamycin Acetyltransferase

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