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Mechanisms of Resistance

Detection of grlA and gyrA Mutations in 344 Staphylococcus aureus Strains

Tong Wang, Mayumi Tanaka, Kenichi Sato
Tong Wang
New Product Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo 134, Japan
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Mayumi Tanaka
New Product Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo 134, Japan
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Kenichi Sato
New Product Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo 134, Japan
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DOI: 10.1128/AAC.42.2.236
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ABSTRACT

Mutations in the grlA and gyrA genes of 344 clinical strains of Staphylococcus aureus isolated in 1994 in Japan were identified by combinations of single-strand conformation polymorphism analysis, restriction fragment length analysis, and direct sequencing to identify possible relationships to fluoroquinolone resistance. Five types of single-point mutations and four types of double mutations were observed in the grlA genes of 204 strains (59.3%). Four types of single-point mutations and four types of double mutations were found in the gyrA genes of 188 strains (54.7%). Among them, the grlA mutation of TCC→TTC or TAC (Ser-80→Phe or Tyr) and the gyrAmutation of TCA→TTA (Ser-84→Leu) were principal, being detected in 137 (39.8%) and 121 (35.9%) isolates, respectively. ThegrlA point mutations of CAT→CAC (His-77 [silent]), TCA→CCA (Ser-81→Pro), and ATA→ATT (Ile-100 [silent]) were novel, as was the GAC→GGC (Asp-73→Gly) change in gyrA. A total of 15 types of mutation combinations within both genes were related to ciprofloxacin resistance (MIC ≥ 3.13 μg/ml) and were present in 193 mutants (56.1%). Strains containing mutations in both genes were highly resistant to ciprofloxacin (MIC at which 50% of the isolates are inhibited [MIC50] = 50 μg/ml). Those with the Ser-80→Phe or Tyr alteration in grlA but wild-typegyrA showed a lower level of ciprofloxacin resistance (MIC50 ≤ 12.5 μg/ml). Levofloxacin was active against 68 of 193 isolates (35.2%) with mutations at codon 80 of grlAin the presence or absence of a concomitant mutation at codon 73, 84, or 88 in gyrA (MIC ≤ 6.25 μg/ml). The new fluoroquinolone DU-6859a showed good activity with 186 of 193 isolates (96.4%) for which the MIC was ≤6.25 μg/ml.

  • Copyright © 1998 American Society for Microbiology
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Detection of grlA and gyrA Mutations in 344 Staphylococcus aureus Strains
Tong Wang, Mayumi Tanaka, Kenichi Sato
Antimicrobial Agents and Chemotherapy Feb 1998, 42 (2) 236-240; DOI: 10.1128/AAC.42.2.236

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Detection of grlA and gyrA Mutations in 344 Staphylococcus aureus Strains
Tong Wang, Mayumi Tanaka, Kenichi Sato
Antimicrobial Agents and Chemotherapy Feb 1998, 42 (2) 236-240; DOI: 10.1128/AAC.42.2.236
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KEYWORDS

Bacterial Proteins
DNA Topoisomerases, Type II
Genes, Bacterial
Point Mutation
Staphylococcus aureus

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