LETTER
In recent years, Neisseria gonorrhoeae strains with decreased susceptibility (DS; MIC, >0.064 mg/liter) or resistance to cefixime (CFM) or ceftriaxone (CRO), have been classed as “superbugs” and have spread worldwide, resulting in gonorrhea treatment failures (1–3). In N. gonorrhoeae, the genetic mechanisms of mosaic alleles of penA encoding penicillin-binding protein 2 (PBP2), including the fragments of the penA gene from commensal Neisseria spp., mutation of ponA encoding PBP1, mutation of porB1 encoding the outer membrane porin, and mtrR mutations with overexpression of the MtrCDE efflux pump, have also been reported (4–8). As determined by N. gonorrhoeae multiantigen sequence typing (NG-MAST), which is a sequence-based epidemiological approach, strains highly resistant to CRO are known as sequence type 4220 (ST4220) and ST1407 with mosaic penA-X and -XXXIV in Japan and Europe (3, 9). A total of 73 N. gonorrhoeae strains were isolated from male urethritis or female cervicitis cases in Hyogo, Japan, in 2012. The strains were confirmed to be a gonococcal species by testing with the HN-20 Rapid system (Nissui, Tokyo, Japan). The MICs of penicillin G (PEN), CFM, and CRO were determined by the agar dilution method based on CLSI standards (10). Of 73 N. gonorrhoeae isolates tested, 36% were PEN I (intermediate), 64% were PEN R (resistant), 62% were CFM DS, 14% were CFM R, 7% were CRO DS, and 0% were CRO R. Mosaic penA was seen in 78%, including the penA-X family (42%) and the penA-XXXIV family (21%). An L421P mutation in ponA was seen in 100% of the isolates with mosaic penA. The porB1 mutations were G101K and A102D (36%), G101K and A102N (30%), G101 and A102D (1%), and G101T and A102D (1%). A deletion of the mtrR promoter region was seen in 63%, and mtrR mutations (A39T, A40D, and G45D) were seen in 40% (A39T, 12%; A40D, 16%; G45D, 12%). Isolates with mosaic penA (97%, P < 0.001), an L421P mutation in ponA (87%, P < 0.001), porB1 mutations (90%, P < 0.001), or a deletion of the mtrR promoter region (87%, P = 0.004) were significantly associated with CFM DS/R (Table 1). Fifty (74%) of 68 CRO S isolates were classified as CFM DS/R, and all 50 isolates had a mosaic mutation. Furthermore, five isolates with DS to CRO that were typed as NG-MAST ST6798 with penA-X or ST14150 with penA-XXXIV-P551S had ponA and porB1 mutations and a deletion of the mtrR promoter region, respectively (Table 2). ST14150 strains were assigned to genogroup G1407 (11). ST6798 strains, similar to ST2958, were CFM and CRO R in Fukuoka, Japan (12). Shimuta et al. had shown that NG-MAST ST1407 isolates showed a CRO MIC of 0.125 mg/liter and included penA-XXXIV-P551S (1). Genogroup G1407 strains were widespread in China and Spain between 2012 and 2014 (7, 13) and isolated in Hyogo, Japan. In conclusion, on the basis of our findings, even though we have no data on the patients' backgrounds, including demographic data, NG-MAST ST6789 and ST14150 strains in genogroup G1407 had penA mosaic alleles and ponA, porB1, and mtrR mutations and DS to CRO (MIC, >0.064 mg/liter), and these factors may lead to DS to cephalosporins in N. gonorrhoeae in Hyogo, Japan.
Distribution of penA, ponA, porB1, and mtrR mutations among N. gonorrhoeae isolates in different antibiotic susceptibility groupsa
Characteristics of N. gonorrhoeae strains with DS to CROa
ACKNOWLEDGMENTS
We thank Miki Fujiwara and Seiko Nasu for offering gonococcal samples.
This work was partially supported by the Research Program on Emerging and Reemerging Infectious Diseases from the Japan Agency for Medical Research and Development, AMED. This work, including the efforts of Kayo Osawa, was funded by Japan Agency for Medical Research and Development (17fk0108314h0103).
- Copyright © 2017 American Society for Microbiology.
