Emergence and Evolution of Internationally Disseminated Cephalosporin-Resistant Neisseria gonorrhoeae Clones from 1995 to 2005 in Japan

Neisseria gonorrhoeae strains with resistance to extended-spectrum cephalosporins (ESCs), last options for first-line monotherapy of gonorrhoea, likely emerged and initially disseminated in Japan, followed by international transmission. In recent years, multi-locus sequence typing (MLST) ST1901 and N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 isolates with the mosaic penicillin-binding protein (PBP) 2 XXXIV have accounted for most ESC resistance globally. Our aim was to elucidate the initial emergence and transmission of ESC-resistant strains by detailed examination of N. gonorrhoeae isolates from 1995 to 2005 in Kanagawa, Japan.

Already in 1995, one cefixime-resistant (CFM-R) isolate was found, which is the first CFM-R isolate described globally. After 1996, the prevalence of CFM-R and CFM-decreased susceptibility (CFM-DS) isolates significantly increased, with the peak resistance level in 2002 (57.1 % CFM-R). In 1997–2002, the CFM-R MLST ST7363 strain type with the mosaic PBP 2 X was predominant among CFM-R/DS isolates. The first CFM-R/DS MLST ST1901 clone(s), which became the predominant CFM-R/DS strain type(s) already in 2003–2005, possessed the mosaic PBP 2 X, which was possibly originally transferred from the MLST ST7363 strains, and subsequently acquired the mosaic PBP 2 XXXIV. The first MLST ST1901 and NG-MAST ST1407 isolate was identified in Kanagawa already in 2003.

The two main internationally spread cefixime-resistant gonococcal clones, MLST ST7363 and ST1901 (NG-MAST ST1407 most frequent internationally) that also have shown their capacity to develop high-level ceftriaxone resistance (superbugs H041 and F89), likely emerged, evolved and started to disseminate in the metropolitan area, including Kanagawa, in Japan, which was followed by global transmission.

Below:  Molecular epidemiological relatedness of Neisseria gonorrhoeae isolates from 1998 to 2005 in the Kanagawa area, Japan. Minimal spanning tree of 48 MLST STs shows genetic distance of STs derived from 370 isolates. Circle sizes denote the number of isolates sharing the same ST. Black indicates N. gonorrhoeae isolates with resistance or decreased susceptibility to cefixime

Read more at:  http://ht.ly/SmGvU 

By:

Ken Shimuta¹, Yuko Watanabe², Shu-ichi Nakayama¹, Tomoko Morita-Ishihara¹, Toshiro Kuroki², Magnus Unemo³ and Makoto Ohnishi^14*