Novel<i>penA</i>mutations identified in<i>Neisseria gonorrhoeae</i>with decreased susceptibility to ceftriaxone isolated between 2000 and 2014 in Japan

Seike, Kensaku; Yasuda, Mitsuru; Hatazaki, Kyoko; Mizutani, Kosuke; Yuhara, Kazuya; Ito, Yasuhisa; Fujimoto, Yoshinori; Ito, Shin; Tsuchiya, Tomohiro; Yokoi, Shigeaki; Nakano, Masahiro; Deguchi, Takashi

doi:10.1093/jac/dkw161

Cited by 18 publications

(16 citation statements)

References 18 publications

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“…Two SNPs in gyrA were shared (S91F and D95N), and a Ser SNP in parC [ parC (S87I)] was detected only in the male isolate. Finally, while several SNP mutations coincided with phenotypic resistance to azithromycin, ciprofloxacin, and penicillin ( Table 2 ), the single isolate with decreased sensitivity to ceftriaxone (M-3) did not possess the mosaic penA XXXIV allele ( 59 ) or any additional curated mutations that distinguished it from the phenotypically sensitive strains ( Table 2 ) ( 59 , 60 ).…”

Section: Resultsmentioning

confidence: 99%

Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women

Nudel

McClure

Moreau

et al. 2018

mSphere

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Recent emergence of antimicrobial resistance of Neisseria gonorrhoeae worldwide has resulted in limited therapeutic choices for treatment of infections caused by this organism. We performed global transcriptomic analysis of N. gonorrhoeae in subjects with gonorrhea who attended a Nanjing, China, sexually transmitted infection (STI) clinic, where antimicrobial resistance of N. gonorrhoeae is high and increasing. We found that N. gonorrhoeae transcriptional responses to infection differed in genital specimens taken from men and women, particularly antibiotic resistance gene expression, which was increased in men. These sex-specific findings may provide a new approach to guide therapeutic interventions and preventive measures that are also sex specific while providing additional insight to address antimicrobial resistance of N. gonorrhoeae.

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Section: Resultsmentioning

confidence: 99%

Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women

Nudel

McClure

Moreau

et al. 2018

mSphere

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“…For example, 5 isolates in Clade I with elevated MICs to cefixime and ceftriaxone contained the single amino acid substitution A501V in penA, which can enhance ESC MICs [2,20]. Overall, ESC em showed clear associations with specific mosaic PBP2 patterns (eg, X and XXXIV), described in earlier studies, in addition to lesser known patterns such as LXVIII and LXXI [21,[39][40][41]. Similar to a previous study, CFX em isolates with PBP2 pattern XXXIV (61%, 17/28) were observed circulating amongst MSM [42].…”

Section: Cefixime/ Ceftriaxonementioning

confidence: 99%

Evidence of Recent Genomic Evolution in Gonococcal Strains With Decreased Susceptibility to Cephalosporins or Azithromycin in the United States, 2014–2016

Thomas

Kersh

Gernert

et al. 2019

The Journal of Infectious Diseases

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Background. Given the lack of new antimicrobials or a vaccine, understanding the evolutionary dynamics of Neisseria gonorrhoeae is a significant public and global health priority. We investigated the emergence and spread of gonococcal strains with decreased susceptibility to cephalosporins and azithromycin using detailed genomic analyses of gonococcal isolates collected in the United States, 2014-2016.Methods. We sequenced genomes of 649 isolates collected through the Gonococcal Isolate Surveillance Project. We examined the genetic relatedness of isolates and assessed associations between clades and various genotypic and phenotypic combinations.Results. We identified a large and clonal lineage of strains (MLST ST9363) associated with elevated azithromycin minimum inhibitory concentration (AZI em ), characterized by a mosaic mtr locus (C substitution in the mtrR promoter, mosaic mtrR and mtrD). Mutations in 23S rRNA were sporadically distributed among AZI em strains. Another clonal group (MLST ST1901) possessed 7 unique PBP2 patterns, and it shared common mutations in other genes associated with cephalosporin resistance.Conclusions. Whole-genome sequencing methods can enhance monitoring of antimicrobial resistant gonococcal strains by identifying gonococcal populations containing mutations of concern. These methods could inform the development of point-of-care diagnostic tests designed to determine the specific antibiotic susceptibility profile of a gonococcal infection in a patient.

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“…Two SNPs in gyrA were shared (S91F and D95N) and a Ser SNP in parC (S87I) was detected only in the male isolate. Finally, while several SNP mutations coincided with phenotypic resistance to azithromycin, ciprofloxacin and penicillin ( Table 2 ), the single isolate with decreased sensitivity to ceftriaxone (M-3) did not possess the mosaic penA XXXIV allele (59), nor an additional curated mutation(s) that was absent in the phenotypically sensitive strains ( Table 2 ) (59, 60).…”

Section: Resultsmentioning

confidence: 99%

Transcriptome Analysis ofNeisseria gonorrhoeaeDuring Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants Between Men and Women

Nudel

McClure

Moreau

et al. 2018

Preprint

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23Neisseria gonorrhoeae is a bacterial pathogen responsible for the sexually transmitted infection, Importance 46Recent emergence of antimicrobial resistance of Neisseria gonorrhoeae worldwide, has resulted 47 in limited therapeutic choices for treating infections caused by this organism. We performed 48 global transcriptomic analysis of N. gonorrhoeae in subjects with gonorrhea who attended the 49 Nanjing (China) STI clinic where antimicrobial resistance of N. gonorrhoeae is high and 50increasing. We found that N. gonorrhoeae transcriptional responses to infection differed in 51 genital specimens taken from men and women, particularly antibiotic-resistance gene expression, 52 which was increased in men. These sex-specific findings may provide a new approach to guide 53 therapeutic interventions and preventive measures that are also sex-specific while also providing 54 additional insight to address antimicrobial resistance of N. gonorrhoeae.

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NovelpenAmutations identified inNeisseria gonorrhoeaewith decreased susceptibility to ceftriaxone isolated between 2000 and 2014 in Japan

Cited by 18 publications

References 18 publications

Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women

Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women

Evidence of Recent Genomic Evolution in Gonococcal Strains With Decreased Susceptibility to Cephalosporins or Azithromycin in the United States, 2014–2016

Transcriptome Analysis ofNeisseria gonorrhoeaeDuring Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants Between Men and Women

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