Search Results (127)

Introduction: Neisseria gonorrhoeae, a bacterium responsible for gonorrhea, can spread through oral sex, causing pharyngeal gonorrhea, which is also a leading cause of urethritis in outpatient clinics. This study investigated whether tea tree oil (TTO) alone or in combination with other natural products could serve as an effective alternative to chlorhexidine in preventing the spread of oral gonorrhea. Methods: An in vitro model was developed using T84 epithelial cells as a mucosal layer and Neisseria gonorrhoeae strain MS11. The study assessed the minimal inhibitory concentration (MIC), bacterial adherence, invasion, and transmigration across the mucosal barrier. Berberine (BB), a major and bioactive alkaloid derived from Coptis chinensis, was tested with and without TTO in MIC assays and epithelial cell viability tests. Ceftriaxone was used as a positive control. Results: The MIC values for TTO, BB, and ceftriaxone against the MS11 strain were determined to be 0.2%, 5 μg/mL, and 0.0125 μg/mL, respectively. Notably, the combination of TTO with BB demonstrated a synergistic effect, reducing the MIC to 0.000625% TTO + 1.25 μg/mL BB. This combination provided the strongest protective effect. No cytotoxicity was observed in the epithelial cell viability tests for 0.2% diluted TTO, 5 μg/mL BB, or the combination of 0.000625% TTO + 1.25 μg/mL BB. Conclusions: BB, when combined with TTO, exhibited a synergistic antimicrobial effect against Neisseria gonorrhoeae strain MS11 in the T84 mucosal model. These findings highlight the potential of this combination as a natural alternative to chlorhexidine gluconate for managing oral gonorrhea. Full article

Azithromycin remains an important agent in gonorrhea treatment, yet resistance is a growing global threat. To comprehensively define its genetic basis, we performed a large-scale genome-wide association study of 14,727 Neisseria gonorrhoeae genomes with linked azithromycin MICs from 66 countries. We identified 113 genetic variants significantly associated with elevated MICs. Beyond well-known mutations in 23S rRNA (A2059G, C2611T) and mtrCDE operon, we uncovered a broad repertoire of potential resistance determinants, including multiple amino acid substitutions in 16 ribosomal proteins (e.g., L2, L4, L13, L23) forming the nascent peptide exit tunnel (NPET), and porin PorB alterations (G120K, A121D/N). Systematic pairwise analysis revealed extensive synergistic interactions, particularly between variants affecting drug influx/efflux (PorB, MtrCDE) and ribosomal target affinity. Phylogenetic analysis identified successful, globally circulating lineages employing distinct resistance strategies: NPET-dominated, 23S rRNA-associated, and porin/efflux-mediated. Our findings demonstrate that azithromycin resistance is a polygenic trait shaped by functional complementarity and epistasis between target modification, membrane permeability, and efflux. This integrated model is essential for accurate resistance prediction from genomic data and highlights key lineages for focused surveillance. Full article

Background: The surveillance of antimicrobial-resistant (AMR) gonorrhea in the United States is conducted under the Gonococcal Isolate Surveillance Project (GISP). Its protocol involves the collection of urethral isolates from the symptomatic men diagnosed with urethral gonorrhea at designated surveillance sites and the estimation of the percentage of cases resistant to current and former gonorrhea antibiotics. A switch to a new antibiotic is typically made when this percentage for a current first-line drug reaches 5%. However, the cost-effectiveness of this surveillance strategy has never been assessed. Methods: We utilized our previously developed agent-based model of gonorrhea transmission among the US men who have sex with men (MSM) population and estimated the total number of gonorrhea cases, total number of discounted quality-adjusted life years (QALYs) and total discounted costs over 25 years under the current surveillance strategy and under a scenario with no surveillance. Results: The maintenance of the current surveillance strategy is projected to avert 104,108 (95% uncertainty interval: 9163, 213,238) gonorrhea cases, gain 192.9 (95% uncertainty interval: 6, 458.3) QALYs and save $38.6 million (95% uncertainty interval: $1 million, $68.2 million) in the simulated cohort of 10,000 US MSM over a 25-year period (2023–2048) when compared to a scenario with no surveillance. Conclusions: The current US surveillance strategy for AMR gonorrhea is cost-saving. However, the low-bound estimate indicates limited savings of $1 million, which is relatively modest at a national scale. Full article

The rise in antimicrobial-resistant Neisseria gonorrhoeae (NG) strains poses major challenges to gonorrhea treatment worldwide. Ceftriaxone remains the first-line antibiotic therapy; however, emerging resistance, particularly driven by the mosaic penA 60.001 allele, necessitates vigilant surveillance. This study assesses the antimicrobial susceptibility patterns of NG isolates in the northwestern region of Croatia and evaluates the correlation between phenotypic susceptibility testing for extended-spectrum cephalosporins (ESC) and genotypic detection of the penA 60.001 allele. A total of 39 clinical NG-positive specimens by a multiplex PCR panel for urogenital infections were collected between 1 July 2022, and 30 June 2024. Phenotypic antimicrobial susceptibility testing was performed using the Etest method. Genotypic detection of ceftriaxone resistance determinants was performed using a multiplex nested PCR assay. All NG isolates were susceptible to ceftriaxone and cefixime. High resistance rates were observed for ciprofloxacin (70.6%), tetracycline (44.1%), and azithromycin (20.6%). Mutations in the penA gene associated with decreased susceptibility to ceftriaxone were detected in three samples, although phenotypic resistance was not observed. The high resistance rates to ciprofloxacin, tetracycline, and azithromycin limit their use for empirical therapy in Croatia. While ceftriaxone remains effective, the detection of penA mutations highlights the need for ongoing surveillance. Full article

Background: Men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP) experience a high burden of human papillomavirus (HPV) infection and related diseases, yet data on HPV vaccination among this group in Brazil remain limited. Aims: The aims of this study were to estimate the prevalence of complete HPV vaccination and to identify factors associated with vaccination completion among MSM using PrEP in Brazil. Methods: We conducted a cross-sectional online survey between May and September 2025 among MSM aged ≥18 years, residing in Brazil and currently using oral PrEP. Participants were recruited through virtual snowball sampling and targeted advertisements on social media and a gay geosocial networking application. Data were collected using a structured, self-administered questionnaire hosted on REDCap^®. Complete HPV vaccination was defined as self-reported receipt of all doses recommended according to the participant’s age and clinical condition. Sociodemographic characteristics, relationship patterns, sexual behaviors, lubricant use during sexual activity, and history of sexually transmitted infections (STIs) were assessed. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (95% CIs) were estimated using Poisson regression with robust (sandwich) variance. Results: A total of 872 MSM using PrEP were included, of whom 59.4% reported complete HPV vaccination. In adjusted analyses, complete vaccination was more frequent among participants reporting both steady and casual partners (aPR = 1.90; 95% CI: 1.36–2.65) or only casual partners (aPR = 1.72; 95% CI: 1.24–2.39), those reporting lubricant use during sexual activity (aPR = 1.41; 95% CI: 1.23–1.61), and those with a diagnosis of chlamydia and/or gonorrhea in the previous 12 months (aPR = 1.22; 95% CI: 1.08–1.36). Conclusions: Although HPV vaccination coverage among MSM using PrEP in Brazil is higher than that reported for MSM in general, it remains incomplete in a population with regular contact with specialized health services. Integrating systematic assessment and delivery of HPV vaccination into PrEP care may help increase vaccination completion and reduce missed opportunities for prevention. Full article

Background/Objectives: The escalating threat of drug-resistant Neisseria gonorrhoeae underscores the urgent need for novel therapeutic agents. Zoliflodacin, a first-in-class spiropyrimidinetrione antibiotic that targets bacterial DNA gyrase and topoisomerase IV, represents a promising candidate for gonorrhea treatment. Methods: From 2020 to 2023, a total of 876 urogenital N. gonorrhoeae isolates were collected from 35 hospitals across Shanghai, China. In vitro susceptibilities to zoliflodacin and six conventional antibiotics (penicillin, tetracycline, ciprofloxacin, azithromycin, ceftriaxone, and spectinomycin) were determined using the agar dilution method. Whole-genome sequencing was conducted to identify sequence types (STs) and amino-acid substitutions in GyrA, GyrB, ParC, ParE, and MtrR. Results: Zoliflodacin exhibited potent in vitro activity, with minimum inhibitory concentrations (MICs) ranging from ≤0.004 to 0.25 mg/L (MIC₅₀ = 0.06 mg/L; MIC₉₀ = 0.125 mg/L), all below the breakpoint (0.5 mg/L). Notably, zoliflodacin maintained high activity against isolates resistant to ceftriaxone, azithromycin, ciprofloxacin, penicillin, and tetracycline. Although all isolates were susceptible to zoliflodacin, elevated MIC values were observed in ST7363 and ST8123 compared with other clones. Genomic analysis identified no substitutions associated with increased zoliflodacin MICs, and most GyrB sequences, the key gene associated with zoliflodacin resistance, remained intact. Conclusions: These findings demonstrate that zoliflodacin possesses robust activity against circulating multidrug-resistant N. gonorrhoeae lineages in Shanghai and support its potential clinical use for the treatment of gonorrhea. Continued genomic and phenotypic surveillance is warranted to preserve the long-term efficacy of this novel agent. Full article

Background: Adjuvants enhance the immune response to antigens incorporated in vaccine formulations. Given that the majority of infectious agents enter the body through mucosal surfaces, efficacious vaccines must generate protective immunity at these sites, which serve as the first line of defense. There is a need for mucosal adjuvants; hence, we explored the potential of repurposing existing drugs with established safety profiles in humans. Polymyxins are a class of clinically used antibiotics. They are cationic peptides and mast cell activators, which are a novel class of vaccination adjuvants. The goal was to assess the adjuvant properties of Polymyxin B microparticles in combination with vaccine candidates previously developed in our laboratory, such as microparticulate gonorrhea, influenza, measles, Zika, and canine coronavirus vaccines, and to compare their performance with FDA-licensed adjuvants, such as MF59 and Alum. Methods: Polymyxin microparticles were formulated using a double emulsion method, and the toxicity profile and autophagosome generation of Polymyxin B microparticles were assessed. The immunogenic potential of Polymyxin B in these vaccines was studied using multiple parameters such as nitric oxide release using Griess assay and immune profiling using flow cytometry for markers such as MHC I, MHC II, CD40, and CD80. Results: Polymyxin B microparticles were found to be non-cytotoxic to dendritic cells up to 500 μg/mL. Polymyxin B promoted autophagosome formation and nitric oxide release, and showed the upregulation of MHC I, MHC II, CD80, and CD40 pathways. Conclusions: The adjuvant activity of Polymyxin B across various vaccine platforms is significantly comparable to FDA-approved adjuvants, which is a critical requirement for generating T cell responses such as helper T cell and cytotoxic CD8+ T cell responses. Full article

Background/Objectives: Neisseria gonorrhoeae can develop resistance to antimicrobial treatments, posing a challenge to effective management of patients. Alberta, Canada, monitors the antimicrobial susceptibility of gonorrhea isolates to track resistance trends. This study aims to retrospectively analyze susceptibility data and demographic trends from gonorrhea cases in the province over a seven-year period. Methods: Antimicrobial susceptibility testing was performed using gradient strip methodology on gonorrhea isolates from Alberta, evaluating both historical and currently recommended antimicrobials for treatment of gonorrhea. Susceptibility testing results were interpreted using Clinical and Laboratory Standards Institute (CLSI) breakpoints. Provincial antimicrobial susceptibility testing data were analyzed using STATA v.17, incorporating antimicrobial resistance patterns and demographic information from provincial databases. Results: Between 2016 and 2022, 4056 N. gonorrhoeae isolates were cultured from 3617 individuals. All isolates tested were susceptible to ceftriaxone and cefixime, except for a single resistant isolate in 2018. Azithromycin susceptibility ranged from 99% to 88%, with the lowest susceptibility observed in 2018. Males exhibited higher rates of antimicrobial non-susceptibility than females across all drugs tested, except for tetracycline. Conclusions: Ongoing antimicrobial susceptibility surveillance in Alberta is crucial for identifying resistance trends and informing the development of effective treatment strategies for gonorrhea. Full article

The increase in the incidence and antibiotic-resistant strains show a need for a broadly protective vaccine to prevent gonorrhea. OMVax has developed a combination vaccine based on native outer membrane vesicles (NOMVs) from two Neisseria meningitidis (Nm) and two Neisseria gonorrhoeae (Ng) strains. The strains had the acyl transferase LpxL1 knocked out to increase safety, and the reduction-modifiable protein was also knocked out in the Ng strains. Factor H binding protein (FHbp) mutants with reduced Factor H (FH) binding from Subfamilies A and B, respectively, were overexpressed in the Nm strains. The Ng strains individually expressed porin outer membrane protein B 1a (PorB.1a) or PorB.1b. Antibodies elicited by the Nm-Ng NOMV vaccine had SBA with a human complement against diverse Nm and Ng strains grown in the presence of Cytidine-5′-monophospho-N-acetylneuraminic acid (CMP-NANA), had no significant reduction in serum bactericidal activity (SBA) compared to the respective individual vaccines, inhibited the adhesion to human cervical and vaginal cells in five out of six Ng strains tested, and inhibited Nm and Ng colonization in a transgenic mouse model. In conclusion, the Nm-Ng NOMV vaccine has the potential to protect against disease and inhibit colonization by diverse Nm and Ng strains, which may be an advantage for controlling the disease through vaccination, particularly in the adolescent/young adult age group. Full article

Background: Meningococcal B (MenB) vaccination offers protection against invasive meningococcal disease and moderate cross-protection against gonorrhea. However, little is known about coverage and behavioral correlates among men who have sex with men (MSM) in China. This study assessed self-reported MenB vaccination uptake and its associations with sociodemographic and behavioral factors. Methods: We conducted a nationwide cross-sectional survey among 1022 MSM recruited via community-based organizations and online platforms. Vaccination status and recent sexual behaviors were self-reported. Logistic regression identified correlates of uptake, and latent class analysis (LCA) examined behavioral profiles. Results: Participants had a mean age of 29.6 years; most were unmarried (87.7%) and nearly 90% had a college degree or above. Overall, 21.7% reported receiving MenB vaccination. Uptake was positively associated with condomless anal intercourse (aOR = 1.57, 95% CI: 1.08–2.31), group sex (occasionally: aOR = 1.63, 95% CI: 1.01–2.64; frequently: aOR = 3.86, 95% CI: 1.85–8.04), and female partners in the past six months (aOR = 3.69, 95% CI: 2.25–6.10). MSM with multiple casual male partners were less likely to be vaccinated (aOR = 0.55, 95% CI: 0.32–0.93). LCA identified heterogeneous subgroups; notably, the “multi-partner and proactive” group, with high pre-exposure prophylaxis against HIV infection awareness and frequent STI testing, showed low uptake (13.4%). Conclusions: MenB vaccination coverage among MSM in China remained suboptimal. Uptake differed across behavioral subgroups, underscoring the need for stratified, context-specific strategies to inform future vaccine introduction. Full article

Neisseria gonorrhoeae is a Gram-negative diplococcus that causes gonorrhea through sexual contact. This ancient STD remains a major public health concern due to reproductive health impacts, antimicrobial resistance (AMR), and lack of a vaccine. Cannabis sativa contains antibacterial cannabinoids, though its role in combating antibiotic resistance is underexplored. The 2Fe-2S iron–sulfur cluster protein is a potential antibiotic target, as these clusters are vital for bacterial proteins involved in electron transport, enzyme activity, and gene regulation. Disrupting them may impair bacterial survival and function. In this investigation, the 2Fe–2S iron sulfur cluster binding domain-containing protein (NGFG_RS03485), identified as a potential therapeutic target from the core proteome of 12 Neisseria gonorrhoeae strains, was selected for this study. Potential antimicrobial agents were explored through molecular docking studies involving 16 cannabinoid analogs—9 obtained from literature sources and 7 identified via fingerprint similarity searches. The study revealed that four cannabinoids form favorable bonds with active regions against our targeted protein; with a high binding affinity formed from the molecular docking; 1,3-Benzenediol, 2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-, (1R-trans). Dronabinol, Cannabinolic acid A (CBNA), Cannabigerolic acid (CBGA), and Ferruginene C are derivatives identified. Drug-likeness assessments were conducted to evaluate the pharmacokinetic and toxicity properties of the cannabinoids and compared against the antibiotics. Full article

Antimicrobial resistance (AMR) has reached a critical situation globally, prompting urgent national responses to this escalating crisis, including the prioritization of novel antibiotic research. In 2016, Japan initiated a national AMR action plan that promoted appropriate antibiotic use in the country and encouraged a national environment conducive to mitigation measures. However, tackling AMR remains difficult. From an epidemiological perspective, this challenge now extends beyond severe infections, impacting common community-acquired infections, including uncomplicated urinary tract infections (uUTls) and gonorrhea. In uUTIs, the rising prevalence of extended-spectrum β-lactamase-producing and fluoroquinolone-resistant Escherichia coli diminishes the effectiveness of current, routinely used oral antibiotics, necessitating an exploration into innovative solutions. Similarly, the growing resistance of Neisseria gonorrhoeae to antibiotics such as azithromycin raises concerns about the efficacy of current therapeutic options for gonorrhea, which is a highly prevalent sexually transmitted infection. In Japan, since the removal of azithromycin as the recommended first-line treatment, there are no oral first-line antibiotics available to treat gonorrhea. Therefore, novel oral antibiotics are urgently needed for both serious and commonly occurring community-acquired infections. This narrative review discusses the limited availability of novel antibiotics in Japan, the distinctive features of the Japanese antibiotic repertoire and AMR epidemiology, and potential alternative oral treatments for community-acquired infections, including uUTIs and gonorrhea. Japan has been making significant advances toward tackling the AMR crisis through an updated national action plan, AMR policy changes, and innovative approaches to developing novel antibiotics. Substantial international cooperation and the engagement of diverse industry sectors are essential to address the pressing issue of AMR. Full article

Neisseria gonorrhoeae, the causative agent of gonorrhea, represents a major public health concern due to its increasing antimicrobial resistance. While often asymptomatic—particularly in extragenital infections—untreated cases can lead to severe complications and further transmission. Despite global efforts to monitor antimicrobial resistance, data on the molecular determinants underlying decreased susceptibility in N. gonorrhoeae remain scarce in Peru. This study aimed to detect mutations in the penA and 23S rRNA genes, which confer decreased susceptibility to cephalosporins and azithromycin resistance. We extracted DNA from 124 N. gonorrhoeae-positive clinical rectal specimens collected in Aptima Combo 2 transport tubes from MSM patients. These DNA samples were then screened using the Mismatch Amplification Mutation Assay-based real-time PCR (MAMA-qPCR) to identify mutations in the 23S rRNA and penA genes. Each sample underwent separate reactions to detect A2059G and C2611T mutations in the 23S rRNA gene, and 86 of these samples were further tested in individual qPCR assays for the penA D345 deletion (D345del) or G545S mutations. Sanger sequencing was performed on all DNA samples positive for 23S rRNA mutations by MAMA-qPCR assay, and on 27 DNA samples that yielded sufficient penA amplicons for additional sequencing. Using the MAMA-qPCR assay for the 23S rRNA gene, 64 of 124 samples amplified in the A2059G reaction: 2 (3.1%) carried the mutation, and 62 were classified as wild type. In the C2611T reaction, 42 of 124 samples amplified, and none of them carried the mutation. Using the MAMA-qPCR assay for the penA gene, we only analyzed 86 samples, as the remaining 38 samples had insufficient DNA yield. A total of 44 of the 86 samples amplified in the D345del reaction: 5 (11.4%) carried the D345del, and 39 were classified as wild type. In the G545S reaction, 4 (6.4%) carried the mutation, and 58 were classified as wild type. Finally, sequencing of the penA gene in the 27 samples revealed mutations related to decreased susceptibility to cephalosporins. This study identified genetic mutations conferring resistance to azithromycin and decreased susceptibility to cephalosporins, providing an overview of the circulating mutations conferring resistance in N. gonorrhoeae strains in Peru. Full article

Background: The objective of this study is to investigate the prevalence and epidemiological changes of major sexually transmitted infections (STIs) in Korea over the past decade. Methods: From 2010 to 2021, patients diagnosed with STIs based on ICD-10 codes were analyzed using Korean Health insurance data. The analysis included the number of patients, prevalence, and age-specific prevalence (in 5-year intervals) over this period. We examined changes in disease patterns over time by analyzing the annual trends and age-specific prevalence of bacterial STIs such as chlamydia, mycoplasma, gonorrhea, and syphilis; viral STIs such as genital herpes, human papillomavirus (HPV), and human immunodeficiency virus (HIV); and other infections including scabies, pubic lice, and trichomoniasis. Results: In 2010, the STI with the highest prevalence due to an infectious pathogen was trichomoniasis (256.65/100,000), while latent syphilis had the lowest prevalence (5.29/100,000). In 2021, the STI with the highest prevalence was genital herpes (254.54 per 100,000 persons), and latent syphilis continued to have the lowest prevalence. Bacterial STIs showed a decreasing trend. Viral STIs showed a continuous increase throughout the study period, with anogenital warts (AGW) having the highest rate of increase. Other infections showed a decreasing trend. HIV and AGW in men showed a rapid increase. Gender differences varied depending on the disease. Conclusions: While bacterial STIs have gradually declined, viral STIs have continued to increase during last decade. The characteristics of each pathogen vary according to age and gender, necessitating the establishment of risk groups for each pathogen and the development of prevention policies accordingly. Full article

Neisseria gonorrhoeae is the causative agent of the sexually transmitted infection gonorrhea. Preventative vaccines or novel treatments based on a better understanding of the molecular basis of N. gonorrhoeae infection are required as resistance to current antibiotics is widespread. Toxin–antitoxin (TA) systems modulate bacterial physiology by interfering with vital cellular processes; type II TA systems, where both toxin and antitoxin are proteins, are the best-studied. Bioinformatics analysis revealed genes encoding an uncharacterized type II HicAB TA system in the N. gonorrhoeae strain FA1090 chromosome, which were also present in >83% of the other gonococcal genome sequences examined. Gonococcal HicA overproduction inhibited bacterial growth in Escherichia coli, an effect that could be counteracted by the co-expression of HicB. Kill/rescue assays showed that this effect was bacteriostatic rather than bactericidal. The site-directed mutagenesis of key histidine and glycine residues (Gly22, His24, His29) abolished HicA-mediated growth arrest. N. gonorrhoeae FA1090∆hicAB and complemented derivatives that expressed IPTG-inducible hicA, hicB, or hicAB, respectively, grew as wild type, except for IPTG-induced FA1090∆hicAB::hicA. RT-PCR demonstrated that hicAB are transcribed in vitro under the culture conditions used. The deletion of hicAB had no effect on biofilm formation. Our study describes the first characterization of a HicAB TA system in N. gonorrhoeae. Full article