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

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Citation

Ochiai S, Sekiguchi S, Hayashi A, Shimadzu M, Ishiko H, Matsushima-Nishiwaki R, Kozawa O, Yasuda M, Deguchi T

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

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

PubMed ID
17540669 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
CefdinirPenicillin-binding protein 2ProteinNeisseria gonorrhoeae
Yes
Inhibitor
Details