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Nature Reviews. Microbiology Apr 2018The host-adapted human pathogen Neisseria gonorrhoeae is the causative agent of gonorrhoea. Consistent with its proposed evolution from an ancestral commensal bacterium,... (Review)
Review
The host-adapted human pathogen Neisseria gonorrhoeae is the causative agent of gonorrhoea. Consistent with its proposed evolution from an ancestral commensal bacterium, N. gonorrhoeae has retained features that are common in commensals, but it has also developed unique features that are crucial to its pathogenesis. The continued worldwide incidence of gonorrhoeal infection, coupled with the rising resistance to antimicrobials and the difficulties in controlling the disease in developing countries, highlights the need to better understand the molecular basis of N. gonorrhoeae infection. This knowledge will facilitate disease prevention, surveillance and control, improve diagnostics and may help to facilitate the development of effective vaccines or new therapeutics. In this Review, we discuss sex-related symptomatic gonorrhoeal disease and provide an overview of the bacterial factors that are important for the different stages of pathogenesis, including transmission, colonization and immune evasion, and we discuss the problem of antibiotic resistance.
Topics: Adaptation, Physiological; Anti-Bacterial Agents; Drug Resistance, Bacterial; Gonorrhea; Humans; Neisseria gonorrhoeae
PubMed: 29430011
DOI: 10.1038/nrmicro.2017.169 -
Brazilian Journal of Microbiology :... 2017Neisseria gonorrhoeae is the agent of gonorrhea, a sexually transmitted infection with an estimate from The World Health Organization of 78 million new cases in people... (Review)
Review
Neisseria gonorrhoeae is the agent of gonorrhea, a sexually transmitted infection with an estimate from The World Health Organization of 78 million new cases in people aged 15-49 worldwide during 2012. If left untreated, complications may include pelvic inflammatory disease and infertility. Antimicrobial treatment is usually effective; however, resistance has emerged successively through various molecular mechanisms for all the regularly used therapeutic agents throughout decades. Detection of antimicrobial susceptibility is currently the most critical aspect for N. gonorrhoeae surveillance, however poorly structured health systems pose difficulties. In this review, we compiled data from worldwide reports regarding epidemiology and antimicrobial resistance in N. gonorrhoeae, and highlight the relevance of the implementation of surveillance networks to establish policies for gonorrhea treatment.
Topics: Animals; Drug Resistance, Bacterial; Gonorrhea; History, 20th Century; History, 21st Century; Humans; Neisseria gonorrhoeae
PubMed: 28754299
DOI: 10.1016/j.bjm.2017.06.001 -
Revista Chilena de Infectologia :... Jun 2017
Topics: Neisseria gonorrhoeae
PubMed: 28991324
DOI: 10.4067/S0716-10182017000300010 -
Microbiology (Reading, England) Jun 2022, the gonococcus, is a pathogen of major public health concern, but sophisticated approaches to gene manipulation are limited for this species. For example, there are...
, the gonococcus, is a pathogen of major public health concern, but sophisticated approaches to gene manipulation are limited for this species. For example, there are few methods for generating markerless mutations, which allow the generation of precise point mutations and deletions without introducing additional DNA sequence. Markerless mutations are central to studying pathogenesis, the spread of antimicrobial resistance (AMR) and for vaccine development. Here we describe the use of as a counter-selectable marker that can be used for markerless mutagenesis in . encodes galactokinase, an enzyme that metabolizes galactose in bacteria that can utilize it as a sole carbon source. GalK can also phosphorylate a galactose analogue, 2-deoxy-galactose (2-DOG), into a toxic, non-metabolisable intermediate, 2-deoxy-galactose-1-phosphate. We utilized this property of GalK to develop a markerless approach for mutagenesis in . We successfully deleted both chromosomally and plasmid-encoded genes, that are important for gonococcal vaccine development and studies of AMR spread. We designed a positive-negative selection cassette, based on an antibiotic resistance marker and , that efficiently rendered susceptible to growth on 2-DOG. We then adapted the -based counter-selection and the use of 2-DOG for markerless mutagenesis, and applied biochemical and phenotypic analyses to confirm the absence of target genes. We show that our markerless mutagenesis method for has a high success rate, and should be a valuable gene editing tool in the future.
Topics: Galactose; Gene Editing; Mutagenesis; Neisseria gonorrhoeae; Plasmids
PubMed: 35763318
DOI: 10.1099/mic.0.001201 -
MBio Jun 2021The bacterium Neisseria gonorrhoeae (Ngo) is the main cause of the sexually transmitted infection gonorrhea. The global incidence of 87 million new Ngo infections each...
The bacterium Neisseria gonorrhoeae (Ngo) is the main cause of the sexually transmitted infection gonorrhea. The global incidence of 87 million new Ngo infections each year, rising infection rates, and the emergence of Ngo strains that are resistant to all clinically recommended antibiotics have raised the specter of untreatable infections (M. Unemo, H. S. Seifert, E. W. Hook, III, S. Hawkes, et al., Nat Rev Dis Primers 5:79, 2019, https://doi.org/10.1038/s41572-019-0128-6). Given their abundance in symptomatic disease, neutrophils are central to both Ngo infection and consequent damage to host tissues. This article highlights present knowledge and the main open questions about Ngo-neutrophil interactions in immunity versus disease pathogenesis.
Topics: Gonorrhea; Humans; Neisseria gonorrhoeae; Neutrophils
PubMed: 34060328
DOI: 10.1128/mBio.00721-21 -
Biomolecules Mar 2021Gonorrhea is one of the most common, but still hidden and insidious, sexually transmitted diseases caused by (). However, the diagnosis and treatment of gonorrhea are...
Gonorrhea is one of the most common, but still hidden and insidious, sexually transmitted diseases caused by (). However, the diagnosis and treatment of gonorrhea are hampered by antigenic variability among , the lack of acquired immunity, and antimicrobial resistance. Further, strains resistant to cephalosporins, including ceftriaxone, the last line of defense, represent a growing threat, which prompted us to develop -specific diagnostic antibodies with broad-spectrum binding to strains to generate gonorrhea-detecting reagents. This study reports the identification of antibodies via bio-panning on cells using scFv-phage libraries. Reformatting the lead scFv-phage Clones 1 and 4 to a multivalent scFv1-Fc-scFv4 maxibody increased the sensitivity by up to 20-fold compared to the single scFv-Fc (maxibody) alone. Moreover, the multivalent maxibody showed broader cross-reactivity with clinical isolates and the ceftriaxone antibiotic-resistant World Health Organization (WHO) reference strain L. In contrast, the selected antibodies in the scFv-phage, maxibody, and multivalent maxibody did not bind to , , and , suggesting the clinical and pharmaceutical diagnostic value of these selected antibodies for gonorrheal infections. The present study illustrates the advantages and potential application of multivalent maxibodies to develop rapid and sensitive diagnostic reagents for infectious diseases and cancer.
Topics: Gonorrhea; Humans; Neisseria gonorrhoeae
PubMed: 33807121
DOI: 10.3390/biom11030484 -
Emerging Infectious Diseases Apr 2018Cephalosporin-resistant Neisseria gonorrhoeae is a major public health concern. N. gonorrhoeae of multiantigen sequence type G1407 and multilocus sequence type 1901 is...
Cephalosporin-resistant Neisseria gonorrhoeae is a major public health concern. N. gonorrhoeae of multiantigen sequence type G1407 and multilocus sequence type 1901 is an internationally spreading cephalosporin-resistant clone. We detected 4 cases of infection with this clone in China and analyzed resistance determinants by using N. gonorrhoeae sequence typing for antimicrobial resistance.
Topics: Anti-Bacterial Agents; Cephalosporins; China; Drug Resistance, Bacterial; Genes, Bacterial; Gonorrhea; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Neisseria gonorrhoeae
PubMed: 29553336
DOI: 10.3201/eid2404.171817 -
PloS One 2019Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is essential for tracking the emergence and spread of AMR strains in local, national and international...
Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is essential for tracking the emergence and spread of AMR strains in local, national and international populations. This is crucial for developing or refining treatment guidelines. N. gonorrhoeae multiantigen sequence typing (NG-MAST) is beneficial for describing the molecular epidemiology of gonococci at national and international levels. Elucidation of AMR determinants to β-lactam drugs, is a means of monitoring the development of resistance. In Ghana, little is known about the current gonococcal AMR prevalence and no characterization of gonococcal isolates has been previously performed. In this study, gonococcal isolates (n = 44) collected from five health facilities in Ghana from 2012 to 2015, were examined using AMR testing, NG-MAST and sequencing of penA. High rates of resistance were identified to tetracycline (100%), benzylpenicillin (90.9%), and ciprofloxacin (81.8%). One isolate had a high cefixime MIC (0.75 μg/ml). Twenty-eight NG-MAST sequence types (STs) were identified, seventeen of which were novel. The isolate with the high cefixime MIC contained a mosaic penA-34 allele and belonged to NG-MAST ST1407, an internationally spreading multidrug-resistant clone that has accounted for most cefixime resistance in many countries. In conclusion, AMR testing, NG-MAST, and sequencing of the AMR determinant penA, revealed high rates of resistance to tetracycline, benzylpenicillin, and ciprofloxacin; as well as a highly diverse population of N. gonorrhoeae in Ghana. It is imperative to continue with enhanced AMR surveillance and to understand the molecular epidemiology of gonococcal strains circulating in Ghana and other African countries.
Topics: Adolescent; Adult; Amino Acid Sequence; Anti-Bacterial Agents; Antigens, Bacterial; Drug Resistance, Bacterial; Female; Genes, Bacterial; Ghana; Humans; Male; Multilocus Sequence Typing; Neisseria gonorrhoeae; Penicillin-Binding Proteins; Phylogeny; Young Adult
PubMed: 31600300
DOI: 10.1371/journal.pone.0223598 -
BMC Infectious Diseases Jun 2021Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are significant public health concerns globally. Nearly no gonococcal AMR data are available from...
BACKGROUND
Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are significant public health concerns globally. Nearly no gonococcal AMR data are available from Central Asia, and no data from Kyrgyzstan has been published. We examined, for the first time, AMR and molecular epidemiology of N. gonorrhoeae isolates cultured in Kyrgyzstan in 2012 and 2017, in order to inform refinements of the Kyrgyz national gonorrhoea management guidelines.
METHODS
N. gonorrhoeae isolates cultured in 2012 (n = 84) and 2017 (n = 72) in Kyrgyzstan were examined. MICs of nine antimicrobials were determined using Etest and, where available, clinical breakpoints from the EUCAST were applied. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was also performed.
RESULTS
The overall resistance levels were high to ciprofloxacin (88.5%), tetracycline (56.9%), benzylpenicillin (39.1%), and kanamycin (4.7%). Resistance to cefixime (0.6%, n = 1 isolate), azithromycin (0.6%, n = 1), and gentamicin (0.6%, n = 1) was rare. No resistance to ceftriaxone or spectinomycin was found. However, the proportion of isolates with decreased susceptibility (MIC = 0.125 mg/L) to ceftriaxone and cefixime was 12.8 and 11.5%, respectively. Gonococcal isolates were assigned 69 sequence types, of which 52 (75.4%) were new.
CONCLUSIONS
The gonococcal population in Kyrgyzstan in 2012 and 2017 showed a high genetic diversity. Ceftriaxone, 500-1000 mg, in combination with azithromycin 2 g or doxycycline, particularly when chlamydial infection has not been excluded, should be recommended as empiric first-line treatment. Spectinomycin 2 g could be an alternative treatment, and given with azithromycin 2 g if pharyngeal gonorrhoea has not been excluded. Fluoroquinolones, aminoglycosides, benzylpenicillin, or tetracyclines should not be used for empiric treatment of gonorrhoea in Kyrgyzstan. Timely updating and high compliance to national gonorrhoea treatment guidelines based on quality-assured AMR data is imperative. Expanded and improved gonococcal AMR surveillance in Kyrgyzstan is crucial.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gonorrhea; Humans; Kyrgyzstan; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Typing; Neisseria gonorrhoeae
PubMed: 34118893
DOI: 10.1186/s12879-021-06262-w -
International Journal of Infectious... Apr 2020The goal of this work was to assess the genetic diversity of Neisseria gonorrhoeae isolates in Russia and Europe and to compare the distribution of the N. gonorrhoeae...
OBJECTIVES
The goal of this work was to assess the genetic diversity of Neisseria gonorrhoeae isolates in Russia and Europe and to compare the distribution of the N. gonorrhoeae multi-antigen sequencing types (NG-MAST) of Russian isolates with that of isolates from European countries.
METHODS
NG-MAST typing was performed for 804 N. gonorrhoeae isolates collected in Russia in 2013-2018. For isolates from European countries, data from the https://pathogen.watch/collection/eurogasp2013 database were used.
RESULTS
Among the isolates from Russia, 296 NG-MAST types were found. A maximum likelihood phylogenetic tree was constructed. Phylogenetic analysis revealed seven major genogroups uniting the most frequent Russian sequence types: G807, G1993, G9476, G14942, G1152, G9486, and G12531.
CONCLUSIONS
The NG-MAST type distribution in Russia differed from that in European countries. Most of the Russian isolates had sequence types that were not found in Europe. Only 33% of the Russian isolates belonged to genogroups established for European countries, and the widespread European genogroup G1407 was represented by only nine isolates. Analysis of the Russian isolates belonging to phylogenetically close European genogroups indicated similarities in drug resistance, although no epidemically dangerous drug-resistant clones were found among the Russian isolates.
Topics: Antigens, Bacterial; Bacterial Typing Techniques; Europe; Genetic Variation; Genotype; Humans; Neisseria gonorrhoeae; Phylogeny; Russia
PubMed: 31978578
DOI: 10.1016/j.ijid.2020.01.020