Genetic characteristics of azithromycin-resistant Neisseria gonorrhoeae collected in Hyogo, Japan during 2015-2019

Makiko Miura; Katsumi Shigemura; Kayo Osawa; Noriko Nakanishi; Ryohei Nomoto; Reo Onishi; Hiroyuki Yoshida; Toru Sawamura; Shiuh Bin Fang; Yi Te Chiang; Shian Ying Sung; Kuan Cho Chen; Takayuki Miyara; Masato Fujisawa

doi:10.1099/jmm.0.001533

Genetic characteristics of azithromycin-resistant Neisseria gonorrhoeae collected in Hyogo, Japan during 2015-2019

Makiko Miura, Katsumi Shigemura, Kayo Osawa, Noriko Nakanishi, Ryohei Nomoto, Reo Onishi, Hiroyuki Yoshida, Toru Sawamura, Shiuh Bin Fang, Yi Te Chiang, Shian Ying Sung, Kuan Cho Chen, Takayuki Miyara, Masato Fujisawa

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2 Citations (Scopus)

Abstract

Introduction. Azithromycin (AZM) is a therapeutic drug for sexually transmitted infections and is used for Neisseria gonorrhoeae when first- and second-line drugs are not available. Recently, the susceptibility of N. gonorrhoeae against AZM has been decreasing worldwide. Hypothesis/Gap Statement. Azithromycin-resistance (AZM-R) rates among N. gonorrhoeae in Japan are increasing, and the gene mutations and epidemiological characteristics of AZM-R in N. gonorrhoeae have not been fully investigated. Aim. We determined the susceptibility to AZM and its correlation with genetic characteristics of N. gonorrhoeae. Methodology. We investigated the susceptibility to AZM and genetic characteristics of N. gonorrhoeae. Mutations in domain V of the 23S rRNA gene and mtrR were examined in 93 isolates, including 13 AZM-R isolates. Spread and clonality were examined using sequence types (STs) of multi-antigen sequence typing for N. gonorrhoeae (NG-MAST), and whole genome analysis (WGA) to identify single nucleotide polymorphisms. Results. The number of AZM-R isolates increased gradually from 2015 to 2019 in Hyogo (P=0.008). C2599T mutations in 23S rRNA significantly increased in AZM-R isolates (P<0.001). NG-MAST ST4207 and ST6762 were frequently detected in AZM-R isolates, and they had higher MICs to AZM from 6 to 24 µg/ml. The phylogenic tree-based WGA showed that all isolates with ST4207 were contained in the same clade, and isolates with ST6762 were divided into two clades, AZM-S isolates and AZM-R isolates, which were different from the cluster containing ST1407. Conclusion. Our study showed yearly increases in AZM-R rates in N. gonorrhoeae. NG-MAST ST4207 and ST6762 were not detected in our previous study in 2015 and were frequently identified in isolates with higher MICs to AZM. WGA confirmed that isolates with these STs are closely related to each other. Continued surveillance is needed to detect the emergence and confirm the spread of NG-MAST ST4207 and ST6762.

Original language	English
Article number	001533
Journal	Journal of Medical Microbiology
Volume	71
Issue number	6
DOIs	https://doi.org/10.1099/jmm.0.001533
Publication status	Published - 2022

Keywords

23S rRNA
azithromycin resistance
mtrR
Neisseria gonorrhoeae
NG-MAST
WGA

ASJC Scopus subject areas

Microbiology
Microbiology (medical)

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10.1099/jmm.0.001533

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Miura, M., Shigemura, K., Osawa, K., Nakanishi, N., Nomoto, R., Onishi, R., Yoshida, H., Sawamura, T., Fang, S. B., Chiang, Y. T., Sung, S. Y., Chen, K. C., Miyara, T., & Fujisawa, M. (2022). Genetic characteristics of azithromycin-resistant Neisseria gonorrhoeae collected in Hyogo, Japan during 2015-2019. Journal of Medical Microbiology, 71(6), Article 001533. https://doi.org/10.1099/jmm.0.001533

Miura, M, Shigemura, K, Osawa, K, Nakanishi, N, Nomoto, R, Onishi, R, Yoshida, H, Sawamura, T, Fang, SB , Chiang, YT , Sung, SY , Chen, KC, Miyara, T & Fujisawa, M 2022, 'Genetic characteristics of azithromycin-resistant Neisseria gonorrhoeae collected in Hyogo, Japan during 2015-2019', Journal of Medical Microbiology, vol. 71, no. 6, 001533. https://doi.org/10.1099/jmm.0.001533

@article{fcc19380b28141b38a84edfda90bf39e,

title = "Genetic characteristics of azithromycin-resistant Neisseria gonorrhoeae collected in Hyogo, Japan during 2015-2019",

abstract = "Introduction. Azithromycin (AZM) is a therapeutic drug for sexually transmitted infections and is used for Neisseria gonorrhoeae when first- and second-line drugs are not available. Recently, the susceptibility of N. gonorrhoeae against AZM has been decreasing worldwide. Hypothesis/Gap Statement. Azithromycin-resistance (AZM-R) rates among N. gonorrhoeae in Japan are increasing, and the gene mutations and epidemiological characteristics of AZM-R in N. gonorrhoeae have not been fully investigated. Aim. We determined the susceptibility to AZM and its correlation with genetic characteristics of N. gonorrhoeae. Methodology. We investigated the susceptibility to AZM and genetic characteristics of N. gonorrhoeae. Mutations in domain V of the 23S rRNA gene and mtrR were examined in 93 isolates, including 13 AZM-R isolates. Spread and clonality were examined using sequence types (STs) of multi-antigen sequence typing for N. gonorrhoeae (NG-MAST), and whole genome analysis (WGA) to identify single nucleotide polymorphisms. Results. The number of AZM-R isolates increased gradually from 2015 to 2019 in Hyogo (P=0.008). C2599T mutations in 23S rRNA significantly increased in AZM-R isolates (P<0.001). NG-MAST ST4207 and ST6762 were frequently detected in AZM-R isolates, and they had higher MICs to AZM from 6 to 24 µg/ml. The phylogenic tree-based WGA showed that all isolates with ST4207 were contained in the same clade, and isolates with ST6762 were divided into two clades, AZM-S isolates and AZM-R isolates, which were different from the cluster containing ST1407. Conclusion. Our study showed yearly increases in AZM-R rates in N. gonorrhoeae. NG-MAST ST4207 and ST6762 were not detected in our previous study in 2015 and were frequently identified in isolates with higher MICs to AZM. WGA confirmed that isolates with these STs are closely related to each other. Continued surveillance is needed to detect the emergence and confirm the spread of NG-MAST ST4207 and ST6762.",

keywords = "23S rRNA, azithromycin resistance, mtrR, Neisseria gonorrhoeae, NG-MAST, WGA",

author = "Makiko Miura and Katsumi Shigemura and Kayo Osawa and Noriko Nakanishi and Ryohei Nomoto and Reo Onishi and Hiroyuki Yoshida and Toru Sawamura and Fang, {Shiuh Bin} and Chiang, {Yi Te} and Sung, {Shian Ying} and Chen, {Kuan Cho} and Takayuki Miyara and Masato Fujisawa",

note = "Funding Information: K.O. was partially supported by the Research Program on Emerging and Reemerging Infectious Diseases of the Japan Agency for Medical Research and Development, AMED (21fk0108605h0401). Funding Information: K.O. was partially supported by the Research Program on Emerging and Reemerging Infectious Diseases of the Japan Agency for Medical Research and Development, AMED (21fk0108605h0401). We are grateful to Toshiro Shirakawa, Rio Okachi, Miku Kasuya and Naoko Nishii for performing the experiments. Publisher Copyright: {\textcopyright} 2022 The Authors.",

year = "2022",

doi = "10.1099/jmm.0.001533",

language = "English",

volume = "71",

journal = "Journal of Medical Microbiology",

issn = "0022-2615",

publisher = "Microbiology Society",

number = "6",

}

TY - JOUR

T1 - Genetic characteristics of azithromycin-resistant Neisseria gonorrhoeae collected in Hyogo, Japan during 2015-2019

AU - Miura, Makiko

AU - Shigemura, Katsumi

AU - Osawa, Kayo

AU - Nakanishi, Noriko

AU - Nomoto, Ryohei

AU - Onishi, Reo

AU - Yoshida, Hiroyuki

AU - Sawamura, Toru

AU - Fang, Shiuh Bin

AU - Chiang, Yi Te

AU - Sung, Shian Ying

AU - Chen, Kuan Cho

AU - Miyara, Takayuki

AU - Fujisawa, Masato

N1 - Funding Information: K.O. was partially supported by the Research Program on Emerging and Reemerging Infectious Diseases of the Japan Agency for Medical Research and Development, AMED (21fk0108605h0401). Funding Information: K.O. was partially supported by the Research Program on Emerging and Reemerging Infectious Diseases of the Japan Agency for Medical Research and Development, AMED (21fk0108605h0401). We are grateful to Toshiro Shirakawa, Rio Okachi, Miku Kasuya and Naoko Nishii for performing the experiments. Publisher Copyright: © 2022 The Authors.

PY - 2022

Y1 - 2022

N2 - Introduction. Azithromycin (AZM) is a therapeutic drug for sexually transmitted infections and is used for Neisseria gonorrhoeae when first- and second-line drugs are not available. Recently, the susceptibility of N. gonorrhoeae against AZM has been decreasing worldwide. Hypothesis/Gap Statement. Azithromycin-resistance (AZM-R) rates among N. gonorrhoeae in Japan are increasing, and the gene mutations and epidemiological characteristics of AZM-R in N. gonorrhoeae have not been fully investigated. Aim. We determined the susceptibility to AZM and its correlation with genetic characteristics of N. gonorrhoeae. Methodology. We investigated the susceptibility to AZM and genetic characteristics of N. gonorrhoeae. Mutations in domain V of the 23S rRNA gene and mtrR were examined in 93 isolates, including 13 AZM-R isolates. Spread and clonality were examined using sequence types (STs) of multi-antigen sequence typing for N. gonorrhoeae (NG-MAST), and whole genome analysis (WGA) to identify single nucleotide polymorphisms. Results. The number of AZM-R isolates increased gradually from 2015 to 2019 in Hyogo (P=0.008). C2599T mutations in 23S rRNA significantly increased in AZM-R isolates (P<0.001). NG-MAST ST4207 and ST6762 were frequently detected in AZM-R isolates, and they had higher MICs to AZM from 6 to 24 µg/ml. The phylogenic tree-based WGA showed that all isolates with ST4207 were contained in the same clade, and isolates with ST6762 were divided into two clades, AZM-S isolates and AZM-R isolates, which were different from the cluster containing ST1407. Conclusion. Our study showed yearly increases in AZM-R rates in N. gonorrhoeae. NG-MAST ST4207 and ST6762 were not detected in our previous study in 2015 and were frequently identified in isolates with higher MICs to AZM. WGA confirmed that isolates with these STs are closely related to each other. Continued surveillance is needed to detect the emergence and confirm the spread of NG-MAST ST4207 and ST6762.

AB - Introduction. Azithromycin (AZM) is a therapeutic drug for sexually transmitted infections and is used for Neisseria gonorrhoeae when first- and second-line drugs are not available. Recently, the susceptibility of N. gonorrhoeae against AZM has been decreasing worldwide. Hypothesis/Gap Statement. Azithromycin-resistance (AZM-R) rates among N. gonorrhoeae in Japan are increasing, and the gene mutations and epidemiological characteristics of AZM-R in N. gonorrhoeae have not been fully investigated. Aim. We determined the susceptibility to AZM and its correlation with genetic characteristics of N. gonorrhoeae. Methodology. We investigated the susceptibility to AZM and genetic characteristics of N. gonorrhoeae. Mutations in domain V of the 23S rRNA gene and mtrR were examined in 93 isolates, including 13 AZM-R isolates. Spread and clonality were examined using sequence types (STs) of multi-antigen sequence typing for N. gonorrhoeae (NG-MAST), and whole genome analysis (WGA) to identify single nucleotide polymorphisms. Results. The number of AZM-R isolates increased gradually from 2015 to 2019 in Hyogo (P=0.008). C2599T mutations in 23S rRNA significantly increased in AZM-R isolates (P<0.001). NG-MAST ST4207 and ST6762 were frequently detected in AZM-R isolates, and they had higher MICs to AZM from 6 to 24 µg/ml. The phylogenic tree-based WGA showed that all isolates with ST4207 were contained in the same clade, and isolates with ST6762 were divided into two clades, AZM-S isolates and AZM-R isolates, which were different from the cluster containing ST1407. Conclusion. Our study showed yearly increases in AZM-R rates in N. gonorrhoeae. NG-MAST ST4207 and ST6762 were not detected in our previous study in 2015 and were frequently identified in isolates with higher MICs to AZM. WGA confirmed that isolates with these STs are closely related to each other. Continued surveillance is needed to detect the emergence and confirm the spread of NG-MAST ST4207 and ST6762.

KW - 23S rRNA

KW - azithromycin resistance

KW - mtrR

KW - Neisseria gonorrhoeae

KW - NG-MAST

KW - WGA

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U2 - 10.1099/jmm.0.001533

DO - 10.1099/jmm.0.001533

M3 - Article

C2 - 35700110

AN - SCOPUS:85132050411

SN - 0022-2615

VL - 71

JO - Journal of Medical Microbiology

JF - Journal of Medical Microbiology

IS - 6

M1 - 001533

ER -

Genetic characteristics of azithromycin-resistant Neisseria gonorrhoeae collected in Hyogo, Japan during 2015-2019

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