JAC Advance Access originally published online on May 31, 2007
Journal of Antimicrobial Chemotherapy 2007 60(1):54-60; doi:10.1093/jac/dkm166
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Decreased affinity of mosaic-structure recombinant penicillin-binding protein 2 for oral cephalosporins in Neisseria gonorrhoeae
1 Research and Development Department, Mitsubishi Kagaku Bio-Clinical Laboratories, Inc., 3-30-1 Shimura, Itabashi-Ku, Tokyo 174-8555, Japan 2 Department of Urology, Gifu University School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Japan 3 Department of Pharmacology, Gifu University School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Japan
Received 20 October 2006; returned 7 January 2007; revised 18 April 2007; accepted 22 April 2007
* Corresponding author. Tel: +81-3-5994-2340; Fax: +81-3-5994-2972; E-mail: ochiai.susumu{at}mg.medience.co.jp or s-ochiai{at}nm.mbcl.co.jp
Objectives: In Neisseria gonorrhoeae, the mosaic structure of penicillin-binding protein 2 (PBP 2), composed of fragments of PBP 2 from Neisseria cinerea and Neisseria perflava, was significantly associated with decreased susceptibility to cephalosporins, particularly oral cephalosporins. The aim of this study was to determine the affinity of mosaic PBP 2 for cephalosporins in N. gonorrhoeae.
Methods: Two types of non-mosaic PBP 2 from the type strain of N. gonorrhoeae (ATCC 19424) and a clinical strain (GU01-29), as well as the mosaic PBP 2 from a clinical strain (GU01-89), were expressed in insect cells, and recombinant PBP 2s were purified. ATCC 19424 and GU01-29 were susceptible to cephalosporins. GU01-89 showed decreased susceptibility to cephalosporins. Bindings of fluorescent penicillin to PBP 2 were characterized by the Scatchard plot analysis. The affinity of the recombinant PBP 2s for cefdinir, cefixime and ceftriaxone was determined by PBP 2 competition assays with fluorescent penicillin.
Results: The Kd value of mosaic PBP 2 for fluorescent penicillin was higher than that of non-mosaic PBP 2s. The affinity of mosaic PBP 2 for cefdinir or cefixime was lower than that of the non-mosaic PBP 2s. The affinity of the mosaic PBP 2 for ceftriaxone was not changed, compared with that of the non-mosaic PBP 2s.
Conclusions: Other mechanisms may be involved in clinical isolates with decreased susceptibility to cephalosporins, but this study suggests that the decreased affinity of mosaic-structure recombinant PBP 2 for oral cephalosporins may contribute to decreased susceptibility to these antibiotics in N. gonorrhoeae.
Keywords: mosaic , PBP 2 , cephem , fluorescent penicillin , competition assay
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