The Journal of Medical Microbiology, Vol 42, Issue 3 214-219, Copyright © 1995 by Society for General Microbiology

JOURNAL ARTICLE

Mechanisms of 4-quinolone resistance in quinolone-resistant and methicillin-resistant Staphylococcus aureus isolates from Japan and China

M. Tanaka, Y. X. Zhang, H. Ishida, T. Akasaka, K. Sato and I. Hayakawa
Exploratory Research Laboratories 1, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan.

Ninety-two and 33 methicillin-resistant Staphylococcus aureus (MRSA) strains were isolated in Japan and China respectively. They were categorised as ofloxacin-susceptible (MIC < 12.5 mg/L), moderately (MIC 12.5-25 mg/L) or highly (MIC > or = 50 mg/L) ofloxacin-resistant. 4-Quinolone concentrations required to inhibit purified DNA gyrase from the moderately and highly quinolone-resistant MRSA were at least 20 times higher than those required to inhibit the equivalent enzyme from quinolone-susceptible strains. Reconstitution assays demonstrated that the 4-quinolone-resistant MRSA had a mutation in subunit A of DNA gyrase. A portion of the gyrA gene from amino acids codons 40-115 was sequenced. Four moderately resistant and seven highly resistant MRSA contained a Ser-->Leu substitution at amino acid 84; one moderately and one highly resistant MRSA and one moderately resistant methicillin-susceptible S. aureus (MSSA) strain contained a Glu-->Lys substitution at amino acid 88. Eight MRSA, including one quinolone-susceptible strain and one MSSA contained a silent mutation at amino acid 86. Uptake of ofloxacin in moderately resistant strains was almost the same in the presence or absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), whereas in highly resistant strains, uptake increased when CCCP was added. Restriction fragment length analysis of the norA gene with the restriction endonuclease SfcI showed a mutation of nucleotide position 1085 in all MRSA strains tested except for one highly quinolone-resistant strain. Thus the mechanisms of 4-quinolone-resistance in these MRSA isolates involved alterations in both DNA gyrase and antimicrobial uptake and efflux.

This article has been cited by other articles:

				T. Nagaoka, T. Horii, T. Satoh, T. Ito, A. Monji, A. Takeshita, and M. Maekawa Use of a Three-Dimensional Microarray System for Detection of Levofloxacin Resistance and the mecA Gene in Staphylococcus aureus J. Clin. Microbiol., October 1, 2005; 43(10): 5187 - 5194. [Abstract] [Full Text] [PDF]

				K. Poole Efflux-Mediated Resistance to Fluoroquinolones in Gram-Positive Bacteria and the Mycobacteria Antimicrob. Agents Chemother., October 1, 2000; 44(10): 2595 - 2599. [Full Text]

				C. Bisognano, P. Vaudaux, P. Rohner, D. P. Lew, and D. C. Hooper Induction of Fibronectin-Binding Proteins and Increased Adhesion of Quinolone-Resistant Staphylococcus aureus by Subinhibitory Levels of Ciprofloxacin Antimicrob. Agents Chemother., June 1, 2000; 44(6): 1428 - 1437. [Abstract] [Full Text]

				J. R. Aeschlimann, G. W. Kaatz, and M. J. Rybak The effects of NorA inhibition on the activities of levofloxacin, ciprofloxacin and norfloxacin against two genetically related strains of Staphylococcus aureus in an in-vitro infection model J. Antimicrob. Chemother., September 1, 1999; 44(3): 343 - 349. [Abstract] [Full Text] [PDF]

				J. R. Aeschlimann, L. D. Dresser, G. W. Kaatz, and M. J. Rybak Effects of NorA Inhibitors on In Vitro Antibacterial Activities and Postantibiotic Effects of Levofloxacin, Ciprofloxacin, and Norfloxacin in Genetically Related Strains of Staphylococcus aureus Antimicrob. Agents Chemother., February 1, 1999; 43(2): 335 - 340. [Abstract] [Full Text]

				M. Tanaka, Y. Onodera, Y. Uchida, and K. Sato Quinolone Resistance Mutations in the GrlB Protein of Staphylococcus aureus Antimicrob. Agents Chemother., November 1, 1998; 42(11): 3044 - 3046. [Abstract] [Full Text]

				J. M. Entenza, O. Marchetti, M. P. Glauser, and P. Moreillon Y-688, a New Quinolone Active against Quinolone-Resistant Staphylococcus aureus: Lack of In Vivo Efficacy in Experimental Endocarditis Antimicrob. Agents Chemother., August 1, 1998; 42(8): 1889 - 1894. [Abstract] [Full Text]

				T. Wang, M. Tanaka, and K. Sato Detection of grlA and gyrA Mutations in 344 Staphylococcus aureus Strains Antimicrob. Agents Chemother., February 1, 1998; 42(2): 236 - 240. [Abstract] [Full Text]