Neisseria gonorrhoeae: Antimicrobial Resistance, Genetic Diversity and Potential Therapeutic Arsenal

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (20 September 2022) | Viewed by 10557

Special Issue Editor


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Guest Editor
Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, Moscow, Russia
Interests: infectious agents; gonococcal infection; antimicrobial resistance; multiparametric analysis; molecular diagnostics; biomarkers; molecular epidemiology

Special Issue Information

Dear Colleagues,

Neisseria gonorrhoeae infections belong to the most frequent sexually transmitted infections with more than 80 million new infections globally per annum according to WHO estimations. The steady increase in the resistance of N. gonorrhoeae to antimicrobials strongly impairs the efficacy of gonorrhea treatment and constitutes a significant clinical and public health challenge. Genotyping data associated with susceptibility to antimicrobial drugs are important both for surveillance of gonococcal resistance and for guiding individualized therapy of patients, especially considering the emergence of isolates with decreased susceptibility to cephalosporins and azithromycin. The aim of this Special Issue is to collect original research and review articles focusing on N. gonorrhoeae antimicrobial resistance, pathogenesis, genomic epidemiology and potential future treatment of gonococcal infection. We intend to welcome studies covering development of vaccines and novel substances with bactericidal effect on N. gonorrhoeae. The scope will mainly be on pathogenic N. gonorrhoeae, but we will also welcome relevant work on other Neisseria species, as interaction of commensal Neisseria with N. gonorrhoeae can either drive further development of antimicrobial resistance or lead to the inhibition of the pathogen’s growth.

Dr. Dmitry Gryadunov
Guest Editor

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Keywords

  • antimicrobial resistance
  • pathogenesis
  • genomic surveillance
  • molecular typing
  • host-pathogen interaction
  • new therapeutic antimicrobials
  • gonococcal vaccine candidates
  • commensal Neisseria

Published Papers (4 papers)

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Editorial

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7 pages, 258 KiB  
Editorial
Antibiotic Resistance in Neisseria gonorrhoeae: Challenges in Research and Treatment
by Boris Shaskolskiy, Ilya Kandinov, Ekaterina Dementieva and Dmitry Gryadunov
Microorganisms 2022, 10(9), 1699; https://doi.org/10.3390/microorganisms10091699 - 24 Aug 2022
Cited by 6 | Viewed by 2946
Abstract
Gonococcal infection caused by the Gram-negative bacteria Neisseria gonorrhoeae is one of the most common sexually transmitted infections (STIs) worldwide [...] Full article

Research

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15 pages, 1810 KiB  
Article
Emergence of Azithromycin-Resistant Neisseria gonorrhoeae Isolates Belonging to the NG-MAST Genogroup 12302 in Russia
by Ilya Kandinov, Ekaterina Dementieva, Marina Filippova, Alexandra Vinokurova, Sofya Gorshkova, Alexey Kubanov, Victoria Solomka, Julia Shagabieva, Dmitry Deryabin, Boris Shaskolskiy and Dmitry Gryadunov
Microorganisms 2023, 11(5), 1226; https://doi.org/10.3390/microorganisms11051226 - 6 May 2023
Cited by 3 | Viewed by 1539
Abstract
The goal of this work was to determine the factors affecting the emergence of azithromycin-resistant Neisseria gonorrhoeae isolates in Russia, where azithromycin was never recommended for the treatment of gonococcal infections. Clinical N. gonorrhoeae isolates collected in 2018–2021 (428 isolates) were analyzed. No [...] Read more.
The goal of this work was to determine the factors affecting the emergence of azithromycin-resistant Neisseria gonorrhoeae isolates in Russia, where azithromycin was never recommended for the treatment of gonococcal infections. Clinical N. gonorrhoeae isolates collected in 2018–2021 (428 isolates) were analyzed. No azithromycin-resistant isolates were found in 2018–2019, but in 2020–2021, a significant increase in the ratio of azithromycin-resistant isolates was observed: 16.8% and 9.3%, respectively. A hydrogel DNA microarray was developed for the analysis of resistance determinants: mutations in the genes encoding the mtrCDE efflux system and in all four copies of the 23S rRNA gene (position 2611). A majority of the azithromycin-resistant Russian isolates belonged to the NG-MAST G12302 genogroup, and the resistance was associated with the presence of a mosaic structure of the mtrR gene promoter region with the −35 delA deletion, an Ala86Thr mutation in the mtrR gene, and a mosaic structure of the mtrD gene. A comparative phylogenetic study of modern Russian and European N. gonorrhoeae populations allowed us to conclude that the emergence of azithromycin resistance in Russia in 2020 was the result of the appearance and spread of European N. gonorrhoeae strains belonging to the G12302 genogroup due to possible cross-border transfer. Full article
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12 pages, 957 KiB  
Article
Biochemical Atypia in Russian Neisseria gonorrhoeae Clinical Isolates Belonging to the G807 NG-MAST Genogroup/ST1594 MLST
by Nikita Nosov, Alexey Kubanov, Viktoria Solomka and Dmitry Deryabin
Microorganisms 2022, 10(11), 2271; https://doi.org/10.3390/microorganisms10112271 - 16 Nov 2022
Cited by 2 | Viewed by 1849
Abstract
Many current gonococcal clinical isolates in Russia show atypical taxonomically significant biochemical activity, which leads to species misidentification. Molecular typing of such cultures according Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) and multilocus sequence typing (MLST) protocols assigned them to the G807 NG-MAST GENOGROUP/ST1594 [...] Read more.
Many current gonococcal clinical isolates in Russia show atypical taxonomically significant biochemical activity, which leads to species misidentification. Molecular typing of such cultures according Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) and multilocus sequence typing (MLST) protocols assigned them to the G807 NG-MAST GENOGROUP/ST1594 MLST that has been predominant in Russia in recent years. The goal of the study was to analyze the molecular mechanisms of biochemical atypia in N. gonorrhoeae clinical isolates characterized as the members of G807 NG-MAST GENOGROUP/ST1594 MLST. Sixteen isolates of this genogroup were included in the study, eight showed defective amino acid metabolism or loss of D-glucose fermentation. Comparative bioinformatic analysis based on WGS data divided these isolates into two clusters strictly associated with typical or atypical biochemical activity. Cultures with defective amino acid metabolism had a 5-nucleotide insertion in the pip-gene that caused a stop codon and led to synthesis of the non-functional enzyme. Comparison of the sequenced genomes with publicly available N. gonorrhoeae genomes showed the rarity of this insertion. In the global N. gonorrhoeae phylogenetic tree the G807 NG-MAST GENOGROUP/ST1594 MLST forms a distinct branch characterized by 170 SNPs, most of which are non-synonymous. We hypothesized a unique strategy for G807 NG-MAST GENOGROUP/ST1594 MLST clone persistence in the global N. gonorrhoeae population via escape of antimicrobial therapy due to diagnostic misidentification. Full article
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Review

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14 pages, 924 KiB  
Review
The Optimal Management of Neisseria gonorrhoeae Infections
by Ramona Gabriela Ursu, Ionut Luchian, Costin Damian, Elena Porumb-Andrese, Roxana Gabriela Cobzaru, Giorgio Nichitean, Carmen Ripa, Diana Costin, Darius Sandu, Ioana-Maria Andrioaie and Luminita Smaranda Iancu
Microorganisms 2022, 10(12), 2388; https://doi.org/10.3390/microorganisms10122388 - 1 Dec 2022
Viewed by 3634
Abstract
Neisseria gonorrhoeae is one of the most frequent etiologic agents of STDs (sexually transmitted diseases). Untreated asymptomatic gonococcal infection in women can lead to spreading of the infection in the sexually active population and could lead to late consequences, such as sterility or [...] Read more.
Neisseria gonorrhoeae is one of the most frequent etiologic agents of STDs (sexually transmitted diseases). Untreated asymptomatic gonococcal infection in women can lead to spreading of the infection in the sexually active population and could lead to late consequences, such as sterility or ectopic pregnancies. One important issue about N. gonorrhoeae is its increasing resistance to antibiotics. This paper summarized the newest molecular antimicrobial resistance (AMR) detection assays for Neisseria gonorrhoeae connected with the latest therapeutic antimicrobials and gonococcal vaccine candidates. The assays used to detect AMR varied from the classical minimal inhibitory concentration (MIC) detection to whole-genome sequencing. New drugs against multi drug resistant (MDR) N. gonorrhoeae have been proposed and were evaluated in vivo and in vitro as being efficient in decreasing the N. gonorrhoeae burden. In addition, anti-N. gonorrhoeae vaccine candidates are being researched, which have been assessed by multiple techniques. With the efforts of many researchers who are studying the detection of antimicrobial resistance in this bacterium and identifying new drugs and new vaccine candidates against it, there is hope in reducing the gonorrhea burden worldwide. Full article
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