Dissemination and genome analysis of high-level ceftriaxone-resistant penA 60.001 Neisseria gonorrhoeae strains from the Guangdong Gonococcal antibiotics susceptibility Programme (GD-GASP), 2016-2019

Emerg Microbes Infect. 2022 Dec;11(1):344-350. doi: 10.1080/22221751.2021.2011618.

Abstract

Background: After Neisseria gonorrhoeae FC428 was first found in Japan, ceftriaxone-resistant strains disseminated globally, and the gonococcal resistance rate increased remarkably. Epidemiological investigations are greatly significant for the analysis of antimicrobial resistance (AMR) trends, molecular features and evolution. Objectives: To clarify the AMR trend from 2016-2019 and reveal the molecular characteristics and evolution of ceftriaxone-resistant penA 60.001 isolates. Methods: The minimum inhibitory concentrations (MICs) of antibiotics against 4113 isolates were detected by the agar dilution method. N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST) and N.gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were used to identify the sequence types. Genome analysis was conducted to analyze resistance genes, virulence factors, and evolutionary sources. Results: Isolates with decreased ceftriaxone susceptibility have increased from 2.05% (2016) to 16.18% (2019). Six ceftriaxone-resistant isolates possessing penA 60.001 appeared in Guangdong Province, and were resistant to ceftriaxone, penicillin, tetracycline, ciprofloxacin and cefixime, but susceptible to azithromycin and spectinomycin. Single-nucleotide polymorphisms (SNPs) in the porB gene were the major cause of different NG-MAST types. ST1903 was the main NG-STAR genotype and only strain-ZH545 was ST7365, with molecular features consistent with the MICs. Furthermore, different MLSTs suggested diverse evolutionary sources. Genome analysis revealed a set of virulence factors along with the resistance genes "penA" and "blaTEM-1B". Half of penA 60.001 strains were fully mixed with global FC428-related strains. Conclusions: Global FC428-related clones have disseminated across Guangdong, possibly causing decreased ceftriaxone susceptibility. Enhanced gonococcal surveillance will help elucidate the trajectory of transmission and curb further dissemination.

Keywords: N. gonorrhoeae; ceftriaxone-resistant; epidemiological investigation; penA 60.001.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Azithromycin / pharmacology
  • Ceftriaxone / pharmacology*
  • China / epidemiology
  • Ciprofloxacin / pharmacology
  • Drug Resistance, Bacterial
  • Genome, Bacterial
  • Gonorrhea / drug therapy
  • Gonorrhea / microbiology*
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Epidemiology
  • Multilocus Sequence Typing
  • Neisseria gonorrhoeae / classification
  • Neisseria gonorrhoeae / drug effects*
  • Neisseria gonorrhoeae / genetics
  • Neisseria gonorrhoeae / isolation & purification
  • Spectinomycin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Ciprofloxacin
  • Ceftriaxone
  • Azithromycin
  • Spectinomycin

Grants and funding

This study was supported by grants from the Medical Science and Technolog y Foundation of Guangdong Province (No. B2020149), Guangdong Traditional Chinese Medicine Research Project (No. 202105291302207230), and “Overseas Famous Teacher” Project of Guangdong Provincial Science and Technology Department (No. 2020A1414010136).