Each year, Neisseria gonorrhoeae (Ngo) causes over 1.5 million new infections in the United States, and >87 million worldwide. The absence of a vaccine for preventing gonorrhea, the rapid emergence of multidrug-resistant and extremely drug-resistant Ngo strains, and the limited number of antibiotics available for treating gonorrhea underscore the importance of developing new modalities for addressing Ngo infection. Here, we describe DNA-based microbicides that kill Ngo but not commensals. Previously, we showed that Ngo is killed when it takes up differentially methylated DNA with homology to its genome. We exploited this Achilles heel to develop a new class of microbicides for preventing Ngo infection. These microbicides consist of DNA molecules with specific sequences and a methylation pattern different from Ngo DNA. These DNAs kill low-passage and antibiotic-resistant clinical isolates with high efficiency but leave commensals unharmed. Equally important, the DNAs are equally effective against Ngo whether they are in buffered media or personal lubricants. These findings illustrate the potential of this new class of practical, low-cost, self-administered DNA-based microbicides for preventing Ngo transmission during sexual intercourse.

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To analyze the infection of chlamydia (CT) and gonorrhea (NG) in female infertility and male infertility population, and to explore the correlation between CT and NG infection and infertility. A case-control study was conducted to retrospectively analyze the specimens submitted by patients from the Third Xiangya Hospital of Central South University from January 2021 to December 2022. The results showed that a total of 32 184 specimens were collected, and the positive rates of CT were 4.41% (1 419/32 184), and positive rats of NG were 1.42% (457/32 184). In the infertility group (n=3 366), 2 987 were females and 379 were males. In the control group (n=3 366), 2 509 were females and 857 were males. The CT positive rate of the infertility group was 13.61% (458/3 366), which was significantly higher than that of the control group 3.30% (111/3 366), and the difference was statistically significant (χ2=4.245, P<0.05), and the NG positive rate of the infertility group was 6.36% (214/3 366), which was significantly higher than that of the control group 0.89% (30/3 366), and the difference was statistically significant (χ2=4.011, P<0.05). A total of 23 992 female genital tract swab specimens were collected, including 2 987 in the infertility group and 2 509 in the control group, and the positive rate of CT in the female infertility subgroup was 10.41% (311/2 987), which was significantly higher than that in the control group 3.75% (94/2 509), the difference was statistically significant (χ2=4.132, P<0.05), and the NG positive rate of 8.73% (261/2 987) in the female infertility subgroup was significantly higher than that in the control group 0.40% (10/2 509), and the difference was statistically significant (χ2=4.242, P<0.05). A total of 8 192 male urine samples were collected, including 379 in the infertility group and 857 in the control group, and the CT positive rate of the male infertility subgroup was 13.72% (52/379), which was significantly higher than that of the control group 3.38% (29/857), and the difference was statistically significant (χ2=5.267, P<0.05), and the positive rate of NG in the male infertility subgroup was 12.66% (48/379), which was significantly higher than that of the control group 0.93% (8/857), and the difference was statistically significant (χ2=4.166, P<0.05). Among the 2 987 female specimens in the infertility group, 1 034 were in the primary infertility subgroup and 1 953 were in the secondary infertility subgroup, and the positive rates of CT were 7.93% (82/1 034) and 15.72% (307/1 953), respectively, and the positive rates of NG were 3.87% (40/1 034) and 8.65% (169/1 953) respectively, and the difference was not statistically significant (χ2=0.185, P>0.05) and (χ2=0.002, P>0.05). In conclusion, the infection rate of genital tract CT and NG is high in the infertility population, CT and NG are recommended as routine examination indicators for eugenics and infertility screening.
本研究分析衣原体（CT）和淋球菌（NG）在女性不孕和男性不育人群中的感染情况，探讨CT和NG感染与不孕不育的相关性。采取病例对照研究回顾性分析2021年1月至2022年12月中南大学湘雅三医院患者送检标本的CT和NG结果，初诊为不孕或不育的划分为不孕不育组，同期就诊的近3年内有孕育史的患者系统随机抽样设为对照组，对不同亚组内的CT和NG感染率进行χ2分析。结果显示，总共采集标本32 184份，CT感染率为4.41%（1 419/32 184），NG感染率为1.42%（457/32 184）。在全部标本中，选择将女性首次临床诊断为不孕、男性首次诊断为不育者，划分为不孕不育组（n=3 366），其中女性标本为2 987例，男性标本为379例；在全部标本中，选择同期接受门诊检查的近3年内有孕育史人群系统随机抽样纳入对照组（n=3 366），其中女性标本为2 509例，男性标本为857例。其中不孕不育组的CT感染率13.63%（458/3 366）明显高于对照组3.30%（111/3 366），差异有统计学意义（χ2=4.245，P<0.05），NG感染率6.38%（214/3 366）明显高于对照组0.89%（30/3 366），差异有统计学意义（χ2=4.011，P<0.05）。女性生殖道拭子标本共23 992份，其中不孕组有2 987份，对照组有 2 509份，不孕组的CT感染率10.41%（311/2 987）明显高于对照组3.75%（94/2 509），差异有统计学意义（χ2=4.132，P<0.05），NG感染率8.73%（261/2 987）明显高于对照组0.40%（10/2 509），差异有统计学意义（χ2=4.242，P<0.05）。男性尿液标本共8 192份，其中不育组有379份，对照组有857份，不育组的CT感染率13.72%（52/379）明显高于对照组3.38%（29/857），差异有统计学意义（χ2=5.267，P<0.05），NG感染率12.60%（48/379）明显高于对照组0.93%（8/857），差异有统计学意义（χ2=4.166，P<0.05）。不孕不育组的女性标本2 987例中，原发不孕亚组有1 034例，继发不孕亚组有1 953例，两个亚组中CT感染率分别为7.93%（82/1 034）和15.72%（307/1 953），NG感染率分别为3.87%（40/1 034）和8.65%（169/1 953），比较差异无统计学意义（χ2=0.185，P>0.05）和（χ2=0.002，P>0.05）。综上，生殖道CT和NG在不孕不育人群中感染率较高，建议CT和NG作为优生优育和不孕不育筛查的常规检查指标。.

Neisseria gonorrhoeae is a global threat to public health due to the accumulation of antimicrobial resistance mechanisms. ST-1901 is an internationally important sequence type (ST) because of its high incidence and the usual occurrence of chromosomally determined resistance. In this study, we describe the evolution of the ST-1901 and its single locus variants in Rio de Janeiro from 2006 to 2022. We analyzed 82 N. gonorrhoeae isolates according to antimicrobial susceptibility profile, resistance mechanisms, molecular typing, and phylogenetics. Six different single locus variants were detected. Phylogenetic analysis identified five clades, which share similar characteristics. Resistance rates for penicillin and tetracycline decreased due to the lower occurrence of resistance plasmids, but intermediary resistance to penicillin rose. Resistance to ciprofloxacin remained high throughout all clades and the years of the study. Regarding resistance to azithromycin, alterations in mtrR promoter and gene, and 23S rRNA encoding gene rrl were detected, with a notable rise in the incidence of C2611T mutations in more recent years occurring in 4 out of 5 clades. In contrast, beta-lactam resistance associated penA 34 mosaic was found only in one persisting clade (Clade D), as well as unique G45D and A39T mutations in mtrR gene and its promoter (Nm-Like) were found in only Clade B. Taken together, these data suggest that ST-1901, a persistently circulating lineage of N. gonorrhoeae in Rio de Janeiro, has undergone changes over the years and may evolve to develop resistance to the current recommended dual therapy adopted in Brazil, ceftriaxone and azithromycin.

BACKGROUND: We characterized the antimicrobial resistance (AMR) profiles of Neisseria gonorrhoeae (NG) isolated from symptomatic men at a sexually transmitted infection clinic in Kisumu, Kenya.
METHODS: Two urethral swabs were obtained from symptomatic men between 2020 and 2022, one for Gram\'s stain and the other inoculated directly onto modified Thayer-Martin media containing 1% VCNT and 1% IsoVitaleX enrichment. Culture results were confirmed by colony morphology, Gram\'s stain and oxidase test. Duplicate isolates were shipped to Uniformed Services University for confirmation and characterization. Susceptibility to eight drugs was assessed by E-test. Agar dilution confirmed resistance to ceftriaxone, cefixime, and azithromycin. Susceptibility, intermediate resistance (IR), and resistance (R) were determined according to published criteria.
RESULTS: Of 154 enrolled participants, 112 were culture-positive for NG. Agar dilution results in 110 (98.2%) showed the following: azithromycin-R (1.8%), and 4.5% R or IR to ceftriaxone or cefixime: ceftriaxone-R (0.9%), ceftriaxone-IR (2.7%), and cefixime-IR (2.7%). By E-test, most isolates were IR or R to tetracycline (97.2%), penicillin (90.9%), and ciprofloxacin (95.4%).
CONCLUSIONS: We detected NG with resistance to azithromycin and ceftriaxone, indicating a growing threat to the current Kenyan dual syndromic treatment of urethritis with cephalosporin plus macrolides. Ongoing AMR surveillance is essential for effective drug choices.

OBJECTIVE: To estimate the prevalence of the curable sexually transmitted infections (STIs) Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis and Treponema pallidum, to identify associated risk factors and to assess ciprofloxacin resistance in N. gonorrhoeae-positive specimens among female sex workers (FSWs) in Guinea-Bissau.
METHODS: For this cross-sectional study, FSWs were recruited from October 2014 to May 2019. A questionnaire on STI risk factors was completed by the study participants, and the women were asked to provide a vaginal swab for nucleic acid amplification tests for C. trachomatis, N. gonorrhoeae, M. genitalium, T. vaginalis (Aptima, Hologica), as well as a blood sample for T. pallidum serological testing and discriminatory HIV-testing. The prevalence of STIs was determined, and multivariate logistic regression was used to identify STI risk factors.
RESULTS: The study included 467 women. The prevalence of current infection with any curable STI was 46.7%, and the most common pathogen was T. vaginalis (26.3%), followed by M. genitalium (21.9%), C. trachomatis (11.8%), N. gonorrhoeae (10.1%) and T. pallidum (2.8%). The proportion of asymptomatic infections among the diagnosed STIs was 61.8%, 61.5%, 55.3%, 55.3% and 52.2% for C. trachomatis, T. pallidum, N. gonorrhoeae, T. vaginalis and M. genitalium, respectively. The prevalence of the gyrA S91F mutation conferring ciprofloxacin resistance in N. gonorrhoeae-positive specimens was 84.0%. Significant risk factors for having a curable STI were age and HIV-1 infection, while use of female condoms was a protective factor.
CONCLUSIONS: This study demonstrated that the prevalence of curable STIs was high among FSWs in Guinea-Bissau during the study period, indicating an unmet need for STI services. Moreover, the results indicated that symptomatic treatment might be insufficient, highlighting a need for periodic aetiological testing to facilitate detection of asymptomatic as well as symptomatic STIs to stop ongoing transmission.

The increase in the resistance of mutant strains of Neisseria gonorrhoeae to the antibiotic ceftriaxone is pronounced in the decrease in the second-order acylation rate constant, k2/KS, by penicillin-binding protein 2 (PBP2). These changes can be caused by both the decrease in the acylation rate constant, k2, and the weakening of the binding affinity, i.e., an increase in the substrate constant, KS. A501X mutations in PBP2 affect second-order acylation rate constants. The PBP2A501V variant exhibits a higher k2/KS value, whereas for PBP2A501R and PBP2A501P variants, these values are lower. We performed molecular dynamic simulations with both classical and QM/MM potentials to model both acylation energy profiles and conformational dynamics of four PBP2 variants to explain the origin of k2/KS changes. The acylation reaction occurs in two elementary steps, specifically, a nucleophilic attack by the oxygen atom of the Ser310 residue and C-N bond cleavage in the β-lactam ring accompanied by the elimination of the leaving group of ceftriaxone. The energy barrier of the first step increases for PBP2 variants with a decrease in the observed k2/KS value. Submicrosecond classic molecular dynamic trajectories with subsequent cluster analysis reveal that the conformation of the β3-β4 loop switches from open to closed and its flexibility decreases for PBP2 variants with a lower k2/KS value. Thus, the experimentally observed decrease in the k2/KS in A501X variants of PBP2 occurs due to both the decrease in the acylation rate constant, k2, and the increase in KS.

Development of a vaccine against gonorrhoea is a global priority, driven by the rise in antibiotic resistance. Although Neisseria gonorrhoeae (Ng) infection does not induce substantial protective immunity, highly exposed individuals may develop immunity against re-infection with the same strain. Retrospective epidemiological studies have shown that vaccines containing Neisseria meningitidis (Nm) outer membrane vesicles (OMVs) provide a degree of cross-protection against Ng infection. We conducted a clinical trial (NCT04297436) of 4CMenB (Bexsero, GSK), a licensed Nm vaccine containing OMVs and recombinant antigens, comprising a single arm, open label study of two doses with 50 adults in coastal Kenya who have high exposure to Ng. Data from a Ng antigen microarray established that serum IgG and IgA reactivities against the gonococcal homologs of the recombinant antigens in the vaccine peaked at 10 but had declined by 24 weeks. For most reactive OMV-derived antigens, the reverse was the case. A cohort of similar individuals with laboratory-confirmed gonococcal infection were compared before, during, and after infection: their reactivities were weaker and differed from the vaccinated cohort. We conclude that the cross-protection of the 4CMenB vaccine against gonorrhoea could be explained by cross-reaction against a diverse selection of antigens derived from the OMV component.