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Antimicrobial Agents and Chemotherapy, February 1998, p. 236-240, Vol. 42, No. 2
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Detection of grlA and gyrA Mutations in 344 Staphylococcus aureus Strains

Tong Wang, Mayumi Tanaka,* and Kenichi Sato

New Product Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo 134, Japan

Received 23 June 1997/Returned for modification 15 October 1997/Accepted 25 November 1997

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 TCCright-arrowTTC or TAC (Ser-80right-arrowPhe or Tyr) and the gyrA mutation of TCAright-arrowTTA (Ser-84right-arrowLeu) were principal, being detected in 137 (39.8%) and 121 (35.9%) isolates, respectively. The grlA point mutations of CATright-arrowCAC (His-77 [silent]), TCAright-arrowCCA (Ser-81right-arrowPro), and ATAright-arrowATT (Ile-100 [silent]) were novel, as was the GACright-arrowGGC (Asp-73right-arrowGly) 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-80right-arrowPhe or Tyr alteration in grlA but wild-type gyrA 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 grlA in 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.

* Corresponding author. Mailing address: New Product Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., 16-13 Kitakasai 1-Chome, Edogawa-ku, Tokyo 134, Japan. Phone: 81-3-3680-0151, ext. 5810. Fax: 81-3-5695-8344. E-mail: KYS04512{at}niftyserve.or.jp.

Antimicrobial Agents and Chemotherapy, February 1998, p. 236-240, Vol. 42, No. 2
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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