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J Antimicrob Chemother. 2007 Jul;60(1):54-60. Epub 2007 May 31.

Decreased affinity of mosaic-structure recombinant penicillin-binding protein 2 for oral cephalosporins in Neisseria gonorrhoeae.

Author information

1
Research and Development Department, Mitsubishi Kagaku Bio-Clinical Laboratories, Inc., 3-30-1 Shimura, Itabashi-Ku, Tokyo 174-8555, Japan. ochiai.susumu@mg.medience.co.jp

Abstract

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 K(d) 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.

PMID:
17540669
DOI:
10.1093/jac/dkm166
[Indexed for MEDLINE]

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