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Pathogens
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Neisseria gonorrhoeae Infections
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Neisseria gonorrhoeae Infections

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 44954

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. María-Teresa Pérez-Gracia

E-Mail Website
Guest Editor
Área de Microbiología, Departamento de Farmacia, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, Avenida Seminario s/n, 46113 Moncada, Spain
Interests: antibiotic resistance; drug development; drug repurposing; clinical microbiology
Special Issues, Collections and Topics in MDPI journals
Dr. Beatriz Suay-García

E-Mail Website
Guest Editor
Universidad CEU Cardenal Herrera, Moncada, Spain
Interests: Neisseria gonorrhoeae; Antibiotic resistance; Antibiotic development; QSAR and molecular topology

Special Issue Information

Dear Colleagues,

Gonorrhea is a sexually transmitted disease caused by the obligate human pathogen Neisseria gonorrhoeae. This Gram‐negative diplococcus is highly infective due to its virulence factors: pili, Por proteins, Opa proteins, Rmp proteins, lipooligosaccharides and IgA protease. The most common form of presentation in men is acute anterior urethritis, while gonococcal infection in women does not have specific symptoms. Although the prevailing view is that infections in women are mainly asymptomatic whereas infections in men are not, many studies show that asymptomatic infections are prevalent in both sexes. 

More than 106 million new cases of gonorrhea are estimated to occur yearly worldwide. The highest incidence areas include Africa and the Western Pacific regions. Gonorrhea is primarily transmitted from an infected individual by direct human‐to‐human contact between the mucosal membranes of the urogenital tract, anal canal and the oropharynx, usually during sexual activities. Ever since sulphonamides were introduced to treat gonorrhea in the 1930s, gonococci have continuously shown an extraordinary ability to develop resistance to any antimicrobial introduced for treatment. Treatment is currently given empirically, without performing antimicrobial susceptibility tests. However, the increasing issue of drug‐resistant gonococci has leaded the scientific community to focus research in new drugs and alternative treatments, having obtained encouraging results. The diagnosis of gonorrhea is established by identification of N. gonorrhoeae in genital, rectal, pharyngeal or ocular secretions. N. gonorrhoeae can be detected by culture or nucleic acid amplification tests and, in some cases, Gram staining. Seeing as all attempts to develop a vaccine against gonococci have been unsuccessful, prevention and control of the disease relies completely on early diagnosis, accurate treatment and public health education.

The best knowledge of the molecular mechanisms of this bacterium will facilitate disease prevention, surveillance and control, improve diagnostics and may help to facilitate the development of effective vaccines or new therapeutics.

This Research Topic in Pathogens is dedicated to Neisseria gonorrhoeae Infections. We encourage the submission of original research and review articles, related to:

  • Pathogenesis
  • Colonization and immune evasion
  • Transmission
  • Immunology response
  • Epidemiology
  • Diagnostics
  • Antibiotic resistance mechanisms
  • Antibiotic resistance
  • Current treatment
  • Vaccine
  • Prevention and control

We believe that the Research Topic will give an updated insight into the vibrant field of Neisseria gonorrhoeae, and hope it will serve the purpose to inspire new research activities.

Prof. Dr. María-Teresa Pérez-Gracia
Dr. Beatriz Suay-García
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gonorrhea
  • Neisseria gonorrhoeae
  • pathogenesis
  • antibiotic resistance
  • treatment

Published Papers (7 papers)

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Editorial

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3 pages, 194 KiB  
Editorial
Neisseria gonorrhoeae Infections
by Beatriz Suay-García and María-Teresa Pérez-Gracia
Pathogens 2020, 9(8), 647; https://doi.org/10.3390/pathogens9080647 - 12 Aug 2020
Cited by 2 | Viewed by 3411
Abstract
Gonorrhea is a sexually transmitted disease with a high morbidity burden. Despite having guidelines for its treatment, the incidence of the disease follows an increasing trend worldwide. This is mainly due to the appearance of antibiotic-resistant strains, inefficient diagnostic methods and poor sexual [...] Read more.
Gonorrhea is a sexually transmitted disease with a high morbidity burden. Despite having guidelines for its treatment, the incidence of the disease follows an increasing trend worldwide. This is mainly due to the appearance of antibiotic-resistant strains, inefficient diagnostic methods and poor sexual education. Without an effective vaccine available, the key priorities for the control of the disease include sexual education, contact notification, epidemiological surveillance, diagnosis and effective antibiotic treatment. This Special Issue focuses on some of these important issues such as the molecular mechanisms of the disease, diagnostic tests and different treatment strategies to combat gonorrhea. Full article
(This article belongs to the Special Issue Neisseria gonorrhoeae Infections)

Research

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16 pages, 4280 KiB  
Article
Identification of a Neisseria gonorrhoeae Histone Deacetylase: Epigenetic Impact on Host Gene Expression
by Susu M. Zughaier, Corinne E. Rouquette-Loughlin and William M. Shafer
Pathogens 2020, 9(2), 132; https://doi.org/10.3390/pathogens9020132 - 18 Feb 2020
Cited by 12 | Viewed by 3930
Abstract
Epigenetic reprogramming in macrophages is termed trained innate immunity, which regulates immune tolerance and limits tissue damage during infection. Neisseria gonorrhoeae is a strict human pathogen that causes the sexually transmitted infection termed gonorrhea. Here, we report that this pathogen harbors a gene [...] Read more.
Epigenetic reprogramming in macrophages is termed trained innate immunity, which regulates immune tolerance and limits tissue damage during infection. Neisseria gonorrhoeae is a strict human pathogen that causes the sexually transmitted infection termed gonorrhea. Here, we report that this pathogen harbors a gene that encodes a histone deacetylase-like enzyme (Gc-HDAC) that shares high 3D-homology to human HDAC1, HDAC2 and HDAC8. A Gc-HDAC null mutant was constructed to determine the biologic significance of this gene. The results showed that WT gonococci reduced the expression of host defense peptides LL-37, HBD-1 and SLPI in macrophages when compared to its Gc-HDAC-deficient isogenic strain. The enrichment of epigenetic marks in histone tails control gene expression and are known to change during bacterial infections. To investigate whether gonococci exert epigenetic modifications on host chromatin, the enrichment of acetylated lysine 9 in histone 3 (H3K9ac) was investigated using the TLR-focused ChIP array system. The data showed that infection with WT gonococci led to higher H3K9ac enrichment at the promoters of pro-inflammatory mediators’ genes, many TLRs, adaptor proteins and transcription factors, suggesting gene activation when compared to infection with the Gc-HDAC-deficient mutant. Taken together, the data suggest that gonococci can exert epigenetic modifications on host cells to modulate certain macrophage defense genes, leading to a maladaptive state of trained immunity. Full article
(This article belongs to the Special Issue Neisseria gonorrhoeae Infections)
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8 pages, 211 KiB  
Article
Can Ciprofloxacin be Used for Precision Treatment of Gonorrhea in Public STD Clinics? Assessment of Ciprofloxacin Susceptibility and an Opportunity for Point-of-Care Testing
by Johan H. Melendez, Yu-Hsiang Hsieh, Mathilda Barnes, Justin Hardick, Elizabeth A. Gilliams and Charlotte A. Gaydos
Pathogens 2019, 8(4), 189; https://doi.org/10.3390/pathogens8040189 - 14 Oct 2019
Cited by 9 | Viewed by 4266
Abstract
Background: Given the lack of new antimicrobials to treat Neisseria gonorrhoeae (NG) infections, reusing previously recommended antimicrobials has been proposed as a strategy to control the spread of multi-drug-resistant NG. We assessed ciprofloxacin susceptibility in a large sample set of NG isolates [...] Read more.
Background: Given the lack of new antimicrobials to treat Neisseria gonorrhoeae (NG) infections, reusing previously recommended antimicrobials has been proposed as a strategy to control the spread of multi-drug-resistant NG. We assessed ciprofloxacin susceptibility in a large sample set of NG isolates and identified correlates associated with ciprofloxacin-resistant NG infections. Methods: NG isolates collected in Baltimore, Maryland between 2014 and 2016 were evaluated by Gyrase A (gyrA) PCR and E-test for susceptibility to ciprofloxacin. Clinical characteristics and demographics were evaluated by multivariate regression analysis to identify correlates of ciprofloxacin-resistant NG infections. Results: 510 NG isolates from predominately African American (96.5%), heterosexual (85.7%), and HIV-negative (92.5%) male subjects were included in the study. The overall percentage of isolates with mutant gyrA sequences, indicative of ciprofloxacin resistance, was 32.4%, and significantly increased from 24.7% in 2014 to 45.2% in 2016 (p < 0.001). Participants older than 35 years of age were 2.35 times more likely to have a gyrA mutant NG infection than younger participants (p < 0.001). Race, sexual orientation, symptomology, or co-infection the HIV or syphilis were not associated with a particular NG gyrA genotype. Conclusions: Resistance to ciprofloxacin in Baltimore is lower than other regions and indicates that in this environment, use of ciprofloxacin may be appropriate for targeted treatment provided utilization of enhanced surveillance tools. The targeted use of ciprofloxacin may be more beneficial for individuals under 35 years of age. Point-of-care tests for NG diagnosis and susceptibility testing are urgently needed to identify individuals who can be treated with this targeted approach. Full article
(This article belongs to the Special Issue Neisseria gonorrhoeae Infections)

Review

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7 pages, 391 KiB  
Review
To What Extent Should We Rely on Antibiotics to Reduce High Gonococcal Prevalence? Historical Insights from Mass-Meningococcal Campaigns
by Chris Kenyon
Pathogens 2020, 9(2), 134; https://doi.org/10.3390/pathogens9020134 - 18 Feb 2020
Cited by 3 | Viewed by 2437
Abstract
In the absence of a vaccine, current antibiotic-dependent efforts to reduce the prevalence of Neisseria gonorrhoeae in high prevalence populations have been shown to result in extremely high levels of antibiotic consumption. No randomized controlled trials have been conducted to validate this strategy [...] Read more.
In the absence of a vaccine, current antibiotic-dependent efforts to reduce the prevalence of Neisseria gonorrhoeae in high prevalence populations have been shown to result in extremely high levels of antibiotic consumption. No randomized controlled trials have been conducted to validate this strategy and an important concern of this approach is that it may induce antimicrobial resistance. To contribute to this debate, we assessed if mass treatment in the related species, Neisseria meningitidis, was associated with the emergence of antimicrobial resistance. To this end, we conducted a historical review of the effect of mass meningococcal treatment programmes on the prevalence of N. meningitidis and the emergence of antimicrobial resistance. We found evidence that mass treatment programmes were associated with the emergence of antimicrobial resistance. Full article
(This article belongs to the Special Issue Neisseria gonorrhoeae Infections)
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19 pages, 1494 KiB  
Review
The Laboratory Diagnosis of Neisseria gonorrhoeae: Current Testing and Future Demands
by Thomas Meyer and Susanne Buder
Pathogens 2020, 9(2), 91; https://doi.org/10.3390/pathogens9020091 - 31 Jan 2020
Cited by 46 | Viewed by 15524
Abstract
The ideal laboratory test to detect Neisseria gonorrhoeae (Ng) should be sensitive, specific, easy to use, rapid, and affordable and should provide information about susceptibility to antimicrobial drugs. Currently, such a test is not available and presumably will not be in [...] Read more.
The ideal laboratory test to detect Neisseria gonorrhoeae (Ng) should be sensitive, specific, easy to use, rapid, and affordable and should provide information about susceptibility to antimicrobial drugs. Currently, such a test is not available and presumably will not be in the near future. Thus, diagnosis of gonococcal infections presently includes application of different techniques to address these requirements. Microscopy may produce rapid results but lacks sensitivity in many cases (except symptomatic urogenital infections in males). Highest sensitivity to detect Ng was shown for nucleic acid amplification technologies (NAATs), which, however, are less specific than culture. In addition, comprehensive analysis of antibiotic resistance is accomplished only by in vitro antimicrobial susceptibility testing of cultured isolates. As a light at the end of the tunnel, new developments of molecular techniques and microfluidic systems represent promising opportunities to design point-of-care tests for rapid detection of Ng with high sensitivity and specificity, and there is reason to hope that such tests may also provide antimicrobial resistance data in the future. Full article
(This article belongs to the Special Issue Neisseria gonorrhoeae Infections)
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27 pages, 760 KiB  
Review
Atypical, Yet Not Infrequent, Infections with Neisseria Species
by Maria Victoria Humbert and Myron Christodoulides
Pathogens 2020, 9(1), 10; https://doi.org/10.3390/pathogens9010010 - 20 Dec 2019
Cited by 43 | Viewed by 11248
Abstract
Neisseria species are extremely well-adapted to their mammalian hosts and they display unique phenotypes that account for their ability to thrive within niche-specific conditions. The closely related species N. gonorrhoeae and N. meningitidis are the only two species of the genus recognized as [...] Read more.
Neisseria species are extremely well-adapted to their mammalian hosts and they display unique phenotypes that account for their ability to thrive within niche-specific conditions. The closely related species N. gonorrhoeae and N. meningitidis are the only two species of the genus recognized as strict human pathogens, causing the sexually transmitted disease gonorrhea and meningitis and sepsis, respectively. Gonococci colonize the mucosal epithelium of the male urethra and female endo/ectocervix, whereas meningococci colonize the mucosal epithelium of the human nasopharynx. The pathophysiological host responses to gonococcal and meningococcal infection are distinct. However, medical evidence dating back to the early 1900s demonstrates that these two species can cross-colonize anatomical niches, with patients often presenting with clinically-indistinguishable infections. The remaining Neisseria species are not commonly associated with disease and are considered as commensals within the normal microbiota of the human and animal nasopharynx. Nonetheless, clinical case reports suggest that they can behave as opportunistic pathogens. In this review, we describe the diversity of the genus Neisseria in the clinical context and raise the attention of microbiologists and clinicians for more cautious approaches in the diagnosis and treatment of the many pathologies these species may cause. Full article
(This article belongs to the Special Issue Neisseria gonorrhoeae Infections)
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Other

7 pages, 636 KiB  
Brief Report
Commensal Neisseria Are Shared between Sexual Partners: Implications for Gonococcal and Meningococcal Antimicrobial Resistance
by Christophe Van Dijck, Jolein G. E. Laumen, Sheeba S. Manoharan-Basil and Chris Kenyon
Pathogens 2020, 9(3), 228; https://doi.org/10.3390/pathogens9030228 - 19 Mar 2020
Cited by 6 | Viewed by 2667
Abstract
Antimicrobial resistance in pathogenic Neisseria parallels reduced antimicrobial susceptibility in commensal Neisseria in certain populations, like men who have sex with men (MSM). Although this reduced susceptibility can be a consequence of frequent antimicrobial exposure at the individual level, we hypothesized that commensal [...] Read more.
Antimicrobial resistance in pathogenic Neisseria parallels reduced antimicrobial susceptibility in commensal Neisseria in certain populations, like men who have sex with men (MSM). Although this reduced susceptibility can be a consequence of frequent antimicrobial exposure at the individual level, we hypothesized that commensal Neisseria are transmitted between sexual partners. We used data from a 2014 microbiome study in which saliva and tongue swabs were taken from 21 couples (42 individuals). Samples were analyzed using 16S rRNA gene sequencing. We compared intimate partners with unrelated individuals and found that the oral Neisseria communities of intimate partners were more similar than those of unrelated individuals (average Morisita–Horn dissimilarity index for saliva samples: 0.54 versus 0.71, respectively (p = 0.005); and for tongue swabs: 0.42 versus 0.63, respectively (p = 0.006)). This similarity presumably results from transmission of oral Neisseria through intimate kissing. This finding suggests that intensive gonorrhea screening in MSM may, via increased antimicrobial exposure, promote, rather than prevent, the emergence and spread of antimicrobial resistance in Neisseria. Non-antibiotic strategies such as vaccines and oral antiseptics could prove more sustainable options to reduce gonococcal prevalence. Full article
(This article belongs to the Special Issue Neisseria gonorrhoeae Infections)
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