Analysis of the NH2-terminal 83rd amino acid of Escherichia coli GyrA in quinolone-resistance.
Artificial mutations of Gyrase A protein (GyrA) in Escherichia coli by site-directed mutagenesis were generated to analyze quinolone-resistant mechanisms. By genetic analysis of gyrA genes in a gyrA temperature sensitive (Ts) background, exchange of Ser at the NH2-terminal 83rd position of GyrA to Trp, Leu, Phe, Tyr, Ala, Val, and Ile caused bacterial resistance to the quinolones, while exchange to Gly, Asn, Lys, Arg and Asp did not confer resistance. These results indicate that it is the most important for the 83rd amino acid residue to be hydrophobic in expressing the phenotype of resistance to the quinolones. These findings also suggest that the hydroxyl group of Ser would not play a major role in the quinolone-gyrase interaction and Ser83 would not interact directly with other amino acid residues.
Yonezawa
M
M
Research Laboratories, Toyama Chemical Co., Ltd., Toyama, Japan.
Takahata
M
M
Banzawa
N
N
Matsubara
N
N
Watanabe
Y
Y
Narita
H
H
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001483:Base Sequence; D027081:DNA Gyrase; D017931:DNA Primers / Q000737:chemistry; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000187:drug effects / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D012694:Serine; D013329:Structure-Activity Relationship; D014162:Transfection
D042462:4-Quinolones; D000890:Anti-Infective Agents; D017931:DNA Primers; D012694:Serine; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II