Data compiled by the Centers for Disease Control demonstrates that African American women, in particular young people between the ages of 14-25, have an increased incidence of infection with the sexually transmitted pathogen Neisseria gonorrhoeae. Estradiol is a key regulatory hormone in female reproductive function. It has been studied extensively in the cardiovascular field, and has been linked to breast and endometrial cancers in women. However, its impact on infectious diseases is largely unknown. Given what is known about the effect of estradiol on immunologic and inflammatory disorders in women, I hypothesize that estradiol alters the infectivity of Neisseria gonorrhoeae in the female reproductive tract by altering the host inflammatory immune response. This may explain a risk factor for increased rates of infection in some populations. I sought to develop a relevant in vitro model. After screening a number of candidate cell lines, I selected the human endometrial adenocarcinoma cell line, Ishikawa. These cells express specific estrogen receptors and respond to exogenous estrogen stimulation. Estrogen treatment of Ishikawa cells did not have an impact on the invasion of N. gonorrhoeae, nor did it impact bacterial growth. However, gonococcal induced chemokine secretion was reduced by estrogen, as measured by interleukin-8 secretion. I conclude that estrogen blunts the inflammatory response to Neisseria gonorrhoeae without altering bacterial infectivity.

Globally, the microbe Neisseria gonorrhoeae (NG) causes 106 million newly documented sexually transmitted infections each year. Once appropriately diagnosed, NG infections can be treated with readily available antibiotics, but patients in low-resource settings often do not return to the clinic for results. As current NG diagnostic gold standards suffer from slow turnaround time to result, a rapid, sensitive molecular diagnostic would help increase appropriate treatment at the point-of-care. Here, we report on the design and development of a minimally-instrumented paper-fluidic POC diagnostic that incorporates patient swab sample lysis, isothermal nucleic acid capture, thermophilic helicase-dependent amplification (tHDA), an internal amplification control (NGIC), and lateral flow visual detection. Limits of NG detection for the NG/NGIC multiplex tHDA assay were determined within the device, and device clinical performance was validated retroactively against qPCR-quantified patient samples in a proof-of-concept sensitivity and specificity study. This proof-of-principle paper-fluidic diagnostic, which can be completed within 80 minutes, selectively amplifies and detects NG in multiplex with NGIC. It has a clinically relevant limit of detection of 1000 NG cells per device. In urethral swab sample trials (N=20), the device approaches current gold standard NG diagnostic capabilities with 90% sensitivity and 100% specificity and vaginal swab sample trials (N=20) surpass the gold standard with 100% sensitivity and 100% specificity.

Dissertação (professor titular) - Universidade Federal do Parana, Setor de Ciencias da Saude / Resumo: Os objetivos do presente estudo foram pesquisar a prevalência da bacteria Neisseria gonorrhoeae endocervical em mulheres assintomáticas, usuárias de dispositivo intra-uterino TCu 380A (grupo de estudo - grupo 1) comparando com as usuárias de método anticoncepcional natural ou laqueadura tubária (grupo de controle - grupo 2) e avaliar a percepção da usuária do DIU em relação à informação recebida no serviço. O trabalho foi realizado no Setor de Anticoncepção - Disciplina de Reprodução Humana - Departamento de Tocoginecologia - Universidade Federal do Paraná, no periodo compreendido entre dezembro de 1994 até fevereiro de 1996. A pesquisa constou da avaliação de duzentas pacientes - divididas igualmente nos dois grupos - selecionados aleatoriamente durante o atendimento de rotina nos ambulatórios. O resultado, demonstrou prevalência nula da bactéria Neisseria gonorrhoeae em mulheres assintomáticas de ambos os grupos. A presença de temor de uso do DIU, desconhecimento do método e de seus fatores de risco revelou que a informação recebida foi pouca ou insuficiente para neutralizar as informações que a paciente tinha sobre o método. Sugere-se a necessidade de melhoria do relacionamento médico - paciente para modificar a visão da usuária. / Abstract: The aim of this study is to research the predominance of the endocervical bacteria Neisseria gonorrhoeae in asymptomatic women who use IUDs TCu 380A (group of study - group 1) in comparison with women using natural contraceptive method or tubal ligature (control group - group 2) and to evaluate the perception of the IUD user regarding information received at the clinic. The research was carried out at the Contraception Sector - Human Reproduction Discipline - Tocogynecology Department - Federal University of Paraná, between December of 1994 and February of 1996. The research comprised the evaluation of two hundred patients - divided equally into two groups - selected randomly during the daily routine in the outpatient care. The results showed a null predominance of the bacteria Neisseria gonorrhoeae in asymptomatic women in both groups. The fear of using IUD, the unfamiliarity with the method and its risks revealed that the information received was poor or unsatisfactory for neutralizing information the patients already had about the method. Improvements in the physician-patient relationship are needed to modify the user's point of view.

Submitted by Reginaldo Soares de Freitas (reginaldo.freitas@ufv.br) on 2018-05-25T12:56:00Z No. of bitstreams: 1 texto completo.pdf: 1186028 bytes, checksum: 22a128dd3187d1676fa8c422340d4483 (MD5) / Approved for entry into archive by Reginaldo Soares de Freitas (reginaldo.freitas@ufv.br) on 2018-05-25T12:56:14Z (GMT) No. of bitstreams: 1 texto completo.pdf: 1186028 bytes, checksum: 22a128dd3187d1676fa8c422340d4483 (MD5) / Approved for entry into archive by Reginaldo Soares de Freitas (reginaldo.freitas@ufv.br) on 2018-05-25T12:56:23Z (GMT) No. of bitstreams: 1 texto completo.pdf: 1186028 bytes, checksum: 22a128dd3187d1676fa8c422340d4483 (MD5) / Made available in DSpace on 2018-05-25T12:56:33Z (GMT). No. of bitstreams: 1 texto completo.pdf: 1186028 bytes, checksum: 22a128dd3187d1676fa8c422340d4483 (MD5) Previous issue date: 2017 / Algumas infecções vaginais, como as vaginoses e a infecção por C. Trachomatis, foram associadas ao desenvolvimento de hipertrofia cervical e metaplasia escamosa, indicando uma possível relação com o HPV no desenvolvimento das NICs e carcinoma escamoso do colo uterino. Há na literatura alguns estudos sobre o assunto, ainda sem um consenso definitivo. Nesse sentido, este estudo teve como objetivo investigar a presença de C. trachomatis, N. gonorrhoeae e do papilomavírus humano e suas relações com as lesões cervicais em amostras de citologia cervical, casos e controles, obtidas no ambulatório de ginecologia, do Centro de Especialidades Médicas da Santa Casa de Belo Horizonte. A detecção e genotipagem do HPV, além da detecção da C. trachomatis e N. gonorrhoeaea foram realizadas pela técnica de PCR. Das 186 amostras obtidas, 79 eram o grupo controle e 107 eram do grupo dos casos, portadoras de lesão cervical (38 baixo grau,44 alto grau e 25 CCE). A prevalência de HPV foi 67,7%, da clamídia 19,9% e da gonorreia 3,6%. Os genótipos do HPV mais encontrados foram o HPV 16, 59 e 45. A infecção por mais de um genótipo viral teve associação positiva com a presença de lesões cervicais em geral, e especificamente com lesões de alto grau e câncer. Não houve associação com lesões de baixo grau. As infecções por clamídia e gonorréia, mesmo em associação com HPV, não resultaram em aumento de alterações cervicais. A infecção por N. gonorrhoeaea teve 100% de coinfecção com C.trachomatis, com OR de 5,8 (p<0,0001, 95% IC 4,21-7,99). / Some vaginal infections, such as vaginosis and chlamydia, have been associated with the development of cervical hypertrophy and squamous metaplasia, indicating a possible relationship with HPV in the development of CINs and squamous carcinoma of the cervix. There are some studies in the literature on the subject, still without a definitive consensus. The objective of this study was to investigate the presence of chlamydia trachomatis, neisseria gonorrhoeae and human papillomavirus and their relationship with cervical lesions in cervical cytology samples, cases and controls obtained from Santa Casa Medical Center in Belo Horizonte. HPV detection and genotyping in addition to the detection of C. trachomatis and N. gonorrhoeae were performed by the PCR technique. Of the 186 samples obtained, 79 were the control group and 107 were from the group of cases, with cervical lesions (38 low grade, 44 high grade and 25 CEC). The prevalence of HPV was 67.7%, chlamydia 19.9% and gonorrhea 3.6%. The most common HPV genotypes were HPV 16, 59 and 45. Infection with more than one viral genotype was positively associated with the presence of cervical lesions in general, and specifically with high grade lesions and cancer. There was no association with low grade lesions. Chlamydia and gonorrhea infections, even in association with HPV, did not result in increased cervical changes. N. gonorrhoeaea infection had 100% coinfection with C.trachomatis, with OR of 5.8 (p <0.0001, 95% CI 4.21-7.99). / Não foi apresentado título em inglês. Não foi localizado o cpf do autor.

Purpose of Review: To emphasize key gaps in knowledge impacting efforts to control single infection and co-infections with Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), the most common bacterial sexually transmitted infections (STIs) worldwide. Recent Findings: Clinical and epidemiological studies describe gaps in understanding about female rectal CT infection, screening effectiveness, pelvic inflammatory disease, and influence of the microbiome. For NG, gaps in knowledge include factors increasing incidence in men who have sex with men, correlations between treatment and antibiotic resistance, the role of pharyngeal infection, and microbiome influence. CT/NG co-infections are poorly understood, and adequate models to explore pathophysiological consequences of co-infection urgently needed. The sole existing CT/NG co-infection mouse model showed that CT/NG interactions in vivo modulate host response and NG load/shedding—encouraging further consideration of this model and potential alternatives. Summary: We stress key challenges in controlling these important STIs. Appropriate, quality-assured animal models are essential to improve understanding of the pathogenic interplay in CT/NG co-infections.

Gonorrhea is the second most common sexually transmitted infection worldwide and is caused by Gram-negative, human-specific diplococcus Neisseria gonorrhoeae. It colonizes the mucosal surface of the female reproductive tract and the male urethra. A rapid increase in antibiotic resistance makes gonorrhea a serious threat to public health worldwide. Since N. gonorrhoeae is a human-specific pathogen, animal infection models are not able to recapitulate all the features of infection. Therefore, a realistic in vitro cell culture model is urgently required for studying the gonorrhea infection. In this study, we established and characterized three independent 3D tissue models based on the porcine small intestinal submucosa (SIS) scaffold by co-culturing human dermal fibroblasts with human colorectal carcinoma, endometrial epithelial, and male uroepithelial cells. The histological, immunohistochemical, and ultra-structural analysis showed that the 3D SIS scaffold-based models closely mimic the main characteristics of the site of gonococcal infection in the human host including the formation of epithelial monolayer, underlying connective tissue, mucus production, tight junction (TJ), and microvilli. In addition, functional analysis such as transepithelial electrical resistance (TEER) and barrier permeability indicated high barrier integrity of the cell layer. We infected the established 3D tissue models with different N. gonorrhoeae strains and derivatives presenting various phenotypes regarding adhesion and invasion. The results showed disruption of TJs and growing the interleukins production in response to the infection, which depends on the type of strain and cell. In addition, the 3D tissue models supported bacterial survival, which provided an appropriate in vitro model for long-term infection study. This could be mainly because of the high resilience of the 3D tissue models based on the SIS scaffold to the infection in terms of alteration in permeability, cell destruction, and bacterial transmigration. During gonorrhea infection, a high level of neutrophils migrates to the site of infection. The studies also showed that N. gonorrhoeae can survive or even replicate inside the neutrophils. Therefore, studying the interaction between neutrophils and N. gonorrhoeae is substantially under scrutiny. For this purpose, we generated a 3D tissue model by triple co-culturing of human primary fibroblast cells, human colorectal carcinoma cells, and human umbilical vein endothelial cells. The tissue model was subsequently infected by N. gonorrhoeae. A perfusion-based bioreactor system was employed to recreate blood flow in the side of endothelial cells and consequently study human neutrophils transmigration to the site of infection. We observed neutrophils activation upon the infection. Furthermore, we demonstrated the uptake of N. gonorrhoeae by human neutrophils and reverse transmigration of neutrophils to the basal side carrying N. gonorrhoeae. In summary, the introduced 3D tissue models in this research represent a promising tool to investigate N. gonorrhoeae infections under close-to-natural conditions. / Tripper ist die zweithäufigste sexuell übertragbare Krankheit weltweit und wird durch Gram negative, humanspezifische Diplokokken Neisseria gonorrhoeae verursacht. Das human Pathogen besiedelt die Schleimhautoberfläche des weiblichen Fortpflanzungstraktes und der männlichen Harnröhre. Die rasante Zunahme der Antibiotikaresistenzen macht Gonorrhö zu einer ernsthaften Bedrohung für die öffentliche Gesundheit weltweit. Da N. gonorrhoeae ein humanspezifischer Erreger ist, ist es nicht möglich alle Merkmale einer Infektion in Tiermodellen nachzustellen, daher ist ein realistisches In-vitro-Zellkulturmodell für die Untersuchung der Gonorrhö-Infektion dringend erforderlich. In dieser Studie haben wir drei unabhängige 3D- Gewebemodelle etabliert und charakterisiert, die auf dem Gerüst der Schweine-Submukosa (SIS) basieren, indem wir menschliche dermale Fibroblasten mit menschlichen Darmkrebs-, Endometrialepithel- und männlichen Uroepithelzellen kultivieren. Die histologischen, immunhistochemischen und ultrastrukturellen Analysen zeigten, dass die 3D SIS-Gerüstmodelle die Hauptmerkmale der Stelle der Gonokokken Infektion im menschlichen Wirt genau nachahmen, indem sich Epithelien Monoschichten ausbildeten, unter denen sich Bindegewebe erstrechte. Zudem wiesen die Zellen enge Zell-Zell Kontakte auf und es kam zur Produktion von einer Mukosaschicht sowie Mikrovilli in den Modellen. Darüber hinaus zeigten Funktionsanalysen wie die Messung des transepithelialen elektrischen Widerstands (TEER) und die der Barriere Durchlässigkeit eine hohe Barriere Integrität der Zellschicht. Wir haben die etablierten 3D- Gewebemodelle mit verschiedenen N. gonorrhoeae-Stämmen und Derivaten infiziert, die verschiedene Phänotypen bezüglich der Adhäsion und der Invasion aufwiesen. Die Ergebnisse zeigten eine Unterbrechung der engen Zellverbindungen und eine Zunahme der Interleukin Produktion als Reaktion auf die Infektion, dessen Ausprägung allerdings stark von der Art des Stammes und des verwendeten Zelltyps abhängig ist. Darüber hinaus unterstützten die 3D- Gewebemodelle das bakterielle Überleben, was ein geeignetes In-vitro-Modell für Langzeit- Infektionsstudien liefert. Dies könnte vor allem auf die hohe Widerstandsfähigkeit der SIS- Gerüstmodelle gegen Infektionen in Bezug auf Veränderung der Permeabilität, Zellzerstörung und Bakterienwanderung zurückzuführen sein. Während der Gonorrhoe-Infektion wandert ein hoher Anteil an Neutrophilen an den Ort der Infektion. Die Studie zeigte auch, dass N. gonorrhoeae in den Neutrophilen überleben konnten oder sich sogar in diesen vermehren konnten. Deshalb wurde besonderes die Interaktion zwischen Neutrophilen und N. gonorrhoeae näher betrachtet. Zu diesem Zweck haben wir ein 3D-Gewebemodell mit Hilfe einer dreifache Co-Kultivierung von menschlichen primären Fibroblasten Zellen, menschlichen kolorektalen Karzinomzellen und menschlichen Nabelvenenendothelzellen erstellt. Das Gewebemodell wurde anschließend mit N. gonorrhoeae infiziert. Ein perfusionsbasiertes Bioreaktorsystem wurde eingesetzt, um den Blutfluss auf der Seite der Endothelzellen nachzuahmen und somit konnte die Auswanderung menschlicher Neutrophile zur Infektionsstelle untersucht werden. Darüber hinaus konnte mit diesem Modell die Aufnahme von N. gonorrhoeae in menschliche Neutrophilen und deren Rückwanderung in den Blutfluss beladen mit N. gonorrhoeae nachgewiesen werden. Zusammenfassend lässt sich sagen, dass das in dieser Forschung vorgestellte 3D-Gewebemodell ein vielversprechendes Instrument zur Untersuchung von N. gonorrhoeae-Infektionen unter naturnahen Bedingungen darstellt.

Neisseria gonorrhoeae are Gram-negative bacteria with diplococcal shape. As an obligate human pathogen, it is the causative agent of gonorrhoea, a sexually transmitted disease. Gonococci colonize a variety of mucosal tissues, mainly the urogenital tract in men and women. Occasionally N. gonorrhoeae invades the bloodstream, leading to disseminated gonococcal infection. These bacteria possess a repertoire of virulence factors, which expression patterns can be adapted to the environmental conditions of the host. Through the accumulation of antibiotic resistances and in absence of vaccines, some neisserial strains have the potential to spread globally and represent a major public health threat. Therefore, it is necessary to understand the exact molecular mechanisms underlying the successful infection and progression of gonococci within their host. This deeper understanding of neisserial infection and survival mechanisms is needed for the development of new therapeutic agents. In this work, the role of host-cell sphingolipids on the intracellular survival of N. gonorrhoeae was investigated. It was shown that different classes of sphingolipids strongly interact with invasive gonococci in epithelial cells. Therefore, novel and highly specific clickable sphingolipid analogues were applied to study these interactions with this pathogen. The formation of intra- and extracellular sphingosine vesicles, which were able to target gonococci, was observed. This direct interaction led to the uptake and incorporation of sphingosine into the neisserial membrane. Together with in vitro results, sphingosine was identified as a potential bactericidal reagent as part of the host cell defence. By using different classes of sphingolipids and their clickable analogues, essential structural features, which seem to trigger the bacterial uptake, were detected. Furthermore, effects of key enzymes of the sphingolipid signalling pathway were tested in a neutrophil infection model. In conclusion, the combination of click chemistry and infection biology made it possible to shed some light on the dynamic interplay between cellular sphingosine and N. gonorrhoeae. Thereby, a possible “catch-and-kill” mechanism could have been observed. / Neisseria gonorrhoeae ist ein Gram-negatives Bakterium, welches als Diplokokke vorkommt. Als ein ausschließliches Humanpathogen sind Neisserien der Erreger für die sexuell übertragbare Infektionskrankheit Gonorrhö. Gonokokken besiedeln eine Vielzahl von Schleimhäuten, jedoch hauptsächlich den Urogenitaltrakt bei Männern und Frauen. Gelegentlich kann N. gonorrhoeae in die Blutbahn invadieren, was zu einer disseminierten Infektion führen kann. Diese Bakterien verfügen über ein Repertoire an Virulenzfaktoren, deren Expressionskombination den Umgebungsbedingungen des Wirts angepasst werden können. Durch die Anhäufung von Antibiotikaresistenzen und durch das Fehlen eines Impfstoffes, besteht die Gefahr, dass spezielle Neisserienstämme sich weltweit verbreiten und daher eine ernstzunehmende Bedrohung des Menschen sind. Daher ist es notwendig die zugrundeliegenden molekularen Mechanismen der erfolgreichen Infektion und Ausbreitung der Gonokokken im Wirt genauestens zu verstehen. Das detaillierte Wissen über die Neisserieninfektion und Überlebensmechanismen ist nötig für die Entwicklung neuer Therapieansätze. In dieser Arbeit wurde der Effekt von Sphingolipiden der Wirtszelle auf das intrazelluläre Überleben von N. gonorrhoeae untersucht. Es konnte gezeigt werden, dass unterschiedliche Klassen von Sphingolipiden stark mit invasiven Gonokokken in Epithelzellen interagieren. Um dies zu tun, wurden neue und hochspezifische clickbare Sphingolipidanaloge eingesetzt, um deren Interaktionen mit diesem Pathogen zu studieren. Die Formation von intra- als auch extrazellulären Sphingosinvesikeln, welche Gonokokken gezielt erreichten, konnte beobachtet werden. Diese direkte Interaktion führte zu einer Aufnahme und Einbau des Sphingosins in die Neisserienmembran. Zusammen mit in vitro Ergebnissen, konnte Sphingosin als potenzieller und antibakterieller Bestandteil des zellulären Abwehrsystems identifiziert werden. Weiterhin wurde durch die Verwendung unterschiedlicher Sphingolipidklassen und deren clickbaren Analoge wichtige Strukturen erkannt, die die bakterielle Aufnahme auslösen. Des Weiteren wurden die Auswirkungen von Schlüsselenzymen des Sphingolipidsignalwegs in einem Infektionsmodell mit Neutrophilen getestet. Abschließend ist zu sagen, dass die Kombination aus Click Chemie und Infektionsbiologie es ermöglicht hat, die dynamischen Wechselwirkungen zwischen zellulären Sphingosin und N. gonorrhoeae zu beleuchten. Dadurch konnte ein möglicher „catch-and-kill”-Mechanismus entdeckt werden.

Neisseria gonorrhoeae, the causative agent of gonorrhea, is the second most prevalent sexually transmitted infection that leads to substantial morbidity and economic burden worldwide. Improperly treated or untreated gonorrhea can lead to severe and life-threatening complications, including abortion, infertility, pelvic pain, and maternal death. Neisseria gonorrhoeae has developed resistance to the formally and currently used antibiotics. The Centers for Disease Control and Prevention (CDC) have listed multi-drug resistant N. gonorrhoeae as an urgent threat that promptly requires the development of novel therapeutic agents. Traditional drug discovery and development is a time-consuming and costly process associated with high risks. To address the dire need to replenish the dry pipeline of anti-gonorrhea medications, drug repurposing is a promising approach. In this study, an FDA-approved drug library was screened, and 14 drugs were found to exhibit promising anti-gonococcal activity. Interestingly, three extremely potent and narrow-spectrum novel candidates, itraconazole, isavuconazole, and ravuconazole, are azole antifungals, and their activities were further investigated in vitro. Of the three azoles, ravuconazole displayed the most potent activity against N. gonorrhoeae clinical isolates. The time-kill assay revealed that the three azoles showed bactericidal activity. All three azole drugs showed a low frequency of resistance. Besides, isavuconazole and ravuconazole have a longer post-antibiotic effect than azithromycin. All three azoles cleared the burden of intracellular N. gonorrhoeae completely, which is superior to ceftriaxone. In conclusion, itraconazole, isavuconazole, and ravuconazole merit future investigation for the development of anti-gonorrheal therapeutics. This study provided unexplored avenues and promising opportunities that can be further evaluated to combat N. gonorrhoeae infection. / Master of Science / Neisseria gonorrhoeae, the causative agent of gonorrhea, is the second most prevalent sexually transmitted infection that leads to substantial morbidity and economic burden worldwide. Improperly treated or untreated gonorrhea can lead to severe and life-threatening complications, including abortion, infertility, pelvic pain, and maternal death. Due to the increasing prevalence of drug resistance against the formally and currently used antibiotics, the Centers for Disease Control and Prevention (CDC) have classified multi-drug resistant N. gonorrhoeae as an urgent-threat pathogen. Therefore, the discovery of new anti-gonorrheal therapeutics is an urgent need. Drug repurposing is the process of discovering new therapeutic uses for approved or investigational drugs that go beyond the original medical indication. To address the dire need to replenish the dry pipeline of anti-gonorrheal drugs, repurposing FDA-approved drugs is a promising approach as it significantly reduces the time and expense associated with traditional drug development. By screening an FDA-approved drug library, 14 drugs were found to display promising anti-gonococcal activity. Interestingly, three (itraconazole, isavuconazole, and ravuconazole) out of 14 identified drugs were azole antifungal drugs, and their activities were further investigated in vitro. All three azole drugs showed bactericidal activity, meaning that they killed bacteria, had a low propensity to develop resistance, and completely cleared the burden of intracellular N. gonorrhoeae. Besides, our findings suggested that isavuconazole and ravuconazole possessed exceptional activity in the suppression of bacterial growth following brief antibiotic exposure. In conclusion, the three azole drugs exhibited potent anti-gonococcal activity and merited further investigation. This study provided unexplored avenues and promising opportunities that can be further evaluated to combat multidrug-resistant N. gonorrhoeae. Neisseria gonorrhoeae, the causative agent of gonorrhea, is the second most prevalent sexually transmitted infection that leads to substantial morbidity and economic burden worldwide. Improperly treated or untreated gonorrhea can lead to severe and life-threatening complications, including abortion, infertility, pelvic pain, and maternal death. Due to the increasing prevalence of drug resistance against the formally and currently used antibiotics, the Centers for Disease Control and Prevention (CDC) have classified multi-drug resistant N. gonorrhoeae as an urgent-threat pathogen. Therefore, the discovery of new anti-gonorrheal therapeutics is an urgent need. Drug repurposing is the process of discovering new therapeutic uses for approved or investigational drugs that go beyond the original medical indication. To address the dire need to replenish the dry pipeline of anti-gonorrheal drugs, repurposing FDA-approved drugs is a promising approach as it significantly reduces the time and expense associated with traditional drug development. By screening an FDA-approved drug library, 14 drugs were found to display promising anti-gonococcal activity. Interestingly, three (itraconazole, isavuconazole, and ravuconazole) out of 14 identified drugs were azole antifungal drugs, and their activities were further investigated in vitro. All three azole drugs showed bactericidal activity, meaning that they killed bacteria, had a low propensity to develop resistance, and completely cleared the burden of intracellular N. gonorrhoeae. Besides, our findings suggested that isavuconazole and ravuconazole possessed exceptional activity in the suppression of bacterial growth following brief antibiotic exposure. In conclusion, the three azole drugs exhibited potent anti-gonococcal activity and merited further investigation. This study provided unexplored avenues and promising opportunities that can be further evaluated to combat multidrug-resistant N. gonorrhoeae.

No description available.

Beställningsfrekvensen för detektion av Trichomonas vaginalis samt Mycoplasma genitalium i Jönköpings län är låg jämfört med den för Chlamydia trachomatis och Neisseria gonorrhoeae.  Både T. vaginalis och M. genitalium har associerats med infektion av humant papillomvirus (HPV) samt kan bland annat orsaka salpingit med infertilitet som potentiell komplikation. Patogenerna har även beskrivits öka risken för transmission av HIV. Syftet med studien var att detektera T. vaginalis samt M. genitalium med realtids-Polymerase Chain Reaction (PCR) för uppskattning av prevalens hos individer provtagna för C. trachomatis, N. gonorrhoeae samt HPV i Jönköpings län. Hos individer över 25 år, provtagna för C. trachomatis och N. gonorrhoeae, uppskattades prevalensen till 5,5 % för M. genitalium samt 0,13 % för T. vaginalis. Hos samma individer var prevalensen av C. trachomatis och N. gonorrhoeae 4,5 % respektive 0,13 %. Prevalensen hos individer provtagna för HPV uppskattades till 2,3 % för M. genitalium samt 0,26 % för T. vaginalis. De slutsatser som dras är att relevans finns för en mer frekvent beställning av M. genitalium samt att analys för detektion av endast en patogen ej är optimal. Multiplex analys för detektion av sexuellt överförbara patogener föreslås. / The request for detection of Trichomonas vaginalis and Mycoplasma genitalium in Jönköping County is low compared to Chlamydia trachomatis and Neisseria gonorrhoeae. Both T. vaginalis and M. genitalium have been associated with Human Papilloma Virus (HPV) infection and can cause infections such as salpingitis, potentially resulting in infertility. The pathogens have also been described to increase the risk of HIV transmission. The aim of this study was to detect T. vaginalis and M. genitalium by real-time Polymerase Chain Reaction (PCR) to estimate the prevalence among individuals tested for C. trachomatis, N. gonorrhoeae and HPV in Jönköping County. In individuals above the age of 25 years, tested for C. trachomatis and N. gonorrhoeae, the prevalence was estimated to 5,5 % for M. genitalium and 0,13 % for T. vaginalis. In the same group the prevalence of C. trachomatis and N. gonorrhoeae was 4,5 % and 0,13 % respectively. The prevalence in individuals tested for HPV was estimated to 2,3 % for M. genitalium and 0,26 % for T. vaginalis. Relevance of a more frequent request for detection of M. genitalium was concluded and single pathogen detection was not deemed to be optimal. Multiplex analysis for detection of sexually transmitted pathogens is encouraged.