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Synthesis and Antichlamydial Activity of Novel Benzylaminophenazines Against Chlamydia trachomatis.

A series of phenazine derivatives with C-3 or C-4 benzylamino substituents were synthesized via Buchwald-Hartwig amination and evaluated for antichlamydial activity against Chlamydia trachomatis serovars L2 and D. All compounds exhibited micromolar inhibitory activity, with compound 7d showing the most potent effect (IC50 < 1 μM) but significant host cell cytotoxicity. In contrast, compounds 5g and 7c demonstrated favorable selectivity, with potent antichlamydial activity and no cytotoxicity at 16 μM. Mechanistic studies revealed that 5g and 7c inhibit Chlamydia through a dual mechanism: they …

Epithelial polarity: a key player in Chlamydia trachomatis-host interactions.

Chlamydia trachomatis is a major human pathogen responsible for the most prevalent bacterial sexually transmitted infections. Given its high prevalence, potential for serious complications and high economic burden, understanding the pathogenesis of C. trachomatis infections is crucial for developing effective prevention and treatment strategies. Mucosal epithelial cells serve as the primary replicative niche and play a central role in infection. Historically, research has relied heavily on cancer-derived cell line models to study the interactions of C. trachomatis with host cells. Although the…

Baicalin inhibits Chlamydia trachomatis growth by impairing elementary body infectivity.

Chlamydia trachomatis (C. trachomatis) infection is a prevalent sexually transmitted disease worldwide. Although antibiotics are the standard first-line treatment, the rising incidence of treatment failure highlights the need for alternative therapeutic strategies. Baicalin, a natural flavonoid compound extracted from Scutellaria baicalensis, is known to possess antimicrobial properties. This study aimed to evaluate the anti-chlamydial effects of baicalin. Our results showed that baicalin significantly inhibited the growth of multiple C. trachomatis serovars (A, D, and L2) in HeLa cells, as in…

Разоблачение иммунитета хламидии трахоматис в врожденных секрециях: систематический обзор.

Хламидиотрахоматис (CT) — широко распространенная бактериальная инфекция, передающаяся половым путем (ИППП), связанная с тяжелыми заболеваниями. КТ нацелена на уникальную иммунологическую среду: эпителий гениталия. Хотя выборка гениталий сопряжена с трудностями, предыдущие исследования показали, что антитела, относящиеся к гениталиям, демонстрируют повышенную нейтрализующую способность по сравнению с антителами сыворотки. Кроме того, клетки памяти Т (TRM) обеспечивают более высокую степень защиты по сравнению с циркулирующими Т клетками. Однако необходимы дополнительные исследования для выявле

Совпадение в аннотации оригинала
Chlamydia trachomatis (CT) is a highly prevalent bacterial sexually transmitted infection (STI), associated with severe disease complications. CT targets a unique immunological environment: the genital tract epithelium. Although sampling the genital tract is challenging, previous studies have shown that genital CT-specific antibodies exhibit enhanced neutral…

Chlamydia trachomatis disrupts host metabolism in primary cervical epithelial cells.

Chlamydia trachomatis is a major cause of bacterial sexually transmitted infections and reproductive complications. Despite progress in understanding C. trachomatis pathogenesis, studies using primary cells remain limited. Here, we investigated C. trachomatis infection of cervical epithelial cells and its impact on host cellular processes. Transcriptomic profiling show that C. trachomatis infection in cervical epithelial cells leads to significant changes in host cellular processes, including modulation of immune signaling, attenuation of DNA repair and proliferation-linked signaling pathways,…

GSDMD-mediated pyroptosis restrains intracellular Chlamydia trachomatis growth in macrophages.

Pyroptosis, a type of programmed necrosis associated with inflammatory, is a host defense mechanism against microbial infections. Although Chlamydia has been shown to induce pyroptosis, whether pyroptosis directly impacts the growth of Chlamydia has not been demonstrated. In this study, we found that C. trachomatis L2 infection of the mouse macrophage RAW 264.7 cells induced pyroptosis by monitoring the ultrastructural changes under transmission electron microscopy and the release of LDH and IL-1β. More importantly, this C. trachomatis-triggered pyroptosis with activation of caspase-1 and casp

Immunological Markers of Chlamydia trachomatis Infection in Epithelial Ovarian Cancer.

BACKGROUND/AIM: Pelvic inflammatory disease (PID) is a risk factor for epithelial ovarian cancer (EOC). Chlamydia trachomatis infection, a major cause of PID, may persist in some women. Serum IgG antibodies to chlamydial TroA and HtrA are more common in ascending or repeat chlamydial infection than in uncomplicated infection. The aim of this study was to explore the role of C. trachomatis infection in EOC by analyzing chlamydial TroA, HtrA and major outer membrane protein (MOMP) IgG serum antibody responses. PATIENTS AND METHODS: The study is based on the review of Oulu University Hospital me…

Generation of a novel affibody molecule targeting Chlamydia trachomatis MOMP.

Chlamydia trachomatis (C. trachomatis) is the leading cause of preventable blindness worldwide and the most prevalent cause of bacterial sexually transmitted diseases. At present, there is no available vaccine, and recurrences after antibiotics treatment are substantial problems. Major outer membrane protein (MOMP) accounts for 60% of the outer mass of C. trachomatis, functioning as trimeric porin, and it is highly antigenic. Therefore, MOMP is the most promising candidate for vaccine developing and target therapy of Chlamydia. Affibody, a new class of affinity ligands derived from the Z-domai…

CRISPR Interference To Inducibly Repress Gene Expression in Chlamydia trachomatis.

The ability to inducibly repress gene expression is critical to the study of organisms, like Chlamydia, with reduced genomes in which the majority of genes are likely to be essential. We recently described the feasibility of a CRISPR interference (CRISPRi) system to inducibly repress gene expression in Chlamydia trachomatis. However, the initial system suffered from some drawbacks, primarily leaky expression of the anhydrotetracycline (aTc)-inducible dCas9 ortholog and plasmid instability, which prevented population-wide studies (e.g., transcript analyses) of the effects of knockdown. Here, we…

Liposomal Encapsulation Increases the Efficacy of Azithromycin against Chlamydia trachomatis.

Chlamydia trachomatis (C. trachomatis) is an obligate intracellular bacterium linked to ocular and urogenital infections with potentially serious sequelae, including blindness and infertility. First-line antibiotics, such as azithromycin (AZT) and doxycycline, are effective, but treatment failures have also been reported. Encapsulation of antibiotics in liposomes is considered an effective approach for improving their local effects, bioavailability, biocompatibility and antimicrobial activity. To test whether liposomes could enhance the antichlamydial action of AZT, we encapsulated AZT in diff…

Nonoptimal Vaginal Microbiota After Azithromycin Treatment for Chlamydia trachomatis Infection.

We characterized the composition and structure of the vaginal microbiota in a cohort of 149 women with genital Chlamydia trachomatis infection at baseline who were followed quarterly for 9 months after antibiotic treatment. At time of diagnosis, the vaginal microbiota was dominated by Lactobacillus iners or a diverse array of bacterial vaginosis-associated bacteria including Gardnerella vaginalis. Interestingly, L. iners-dominated communities were most common after azithromycin treatment (1 g monodose), consistent with the observed relative resistance of L. iners to azithromycin. Lactobacillus…

Chlamydia Trachomatis and Human Papillomavirus Serostatus in Puerto Rican Women.

OBJECTIVE: There is a high prevalence of human papillomavirus (HPV) infection in Puerto Rico, but little is known about the prevalence of Chlamydia trachomatis (CT) infection in healthy Puerto Rican women. Thus we aimed to evaluate the seroprevalence and association and the association between HPV and CT. METHODS: This was a secondary data analysis from a cross-sectional, populationbased, study of HPV infection in women aged 16-64 years in Puerto Rico (2010-2013). Enzyme-linked immunosorbent assays (ELISA) were used to detect serum antibodies to CT and HPV. Logistic regression models were use…

Increasing Vaginal Chlamydia Trachomatis Testing in Adolescent and Young Adults.

OBJECTIVE: The Centers for Disease Control and Prevention recommend testing for Chlamydia trachomatis in sexually active female patients <25 years old using nucleic-acid amplification tests (NAAT) from a vaginal swab. Our providers were typically testing using the less sensitive urine NAATs. We aimed to increase the percentage of urogenital C trachomatis NAATs performed by using vaginal swabs in adolescent female patients ages 10 through 20 years from 1.4% to 25%. METHODS: We implemented 3 interventions at 3 pediatric practices over 12 months including education, process standardization, and …

Growth kinetics of Chlamydia trachomatis in primary human Sertoli cells.

Chlamydia trachomatis (Ct) is the leading cause of bacterial sexually transmitted infections worldwide and has been associated with male infertility. Recently, it was hypothesized that Ct may infect the epithelium of the seminiferous tubule, formed by Sertoli cells, thus leading to impaired spermatogenesis. To date, there is a lack of data on Ct infection of the seminiferous epithelium; therefore, we aimed to characterize, for the first time, an in vitro infection model of primary human Sertoli cells. We compared Ct inclusion size, morphology and growth kinetics with those in McCoy cells and w…

Inflammatory mechanism of Chlamydia trachomatis-infected HeLa229 cells regulated by Atg5.

The relation between autophagy and Chlamydia trachomatis infection remain inconclusive. In order to further understand the role of autophagy in C. trachomatis-infected cells. Atg5 silenced HeLa229 cell line was used to establish an autophagy inhibition C. trachomatis infection model. The results suggested that Atg5 served a key regulatory role in the autophagy of C. trachomatis-infected cells. Silencing Atg5 significantly inhibited the autophagy level of the infected cells. Furthermore, Atg5 knockdown led to increased secretion of proinflammatory cytokines IL-1β, IL-6, IFN-γ and TNF-α, and dec…

Urogenital chlamydia trachomatis treatment failure with azithromycin: A meta-analysis.

BACKGROUND: Chlamydia Trachomatis is one of the most common pathogens transmitted through the genital tract in humans that leads to urogenital infection. OBJECTIVE: Given the high prevalence of chlamydia infection and its adverse effects on the health of women and men, the present meta-analysis was conducted to determine the rate of treatment failure with azithromycin. MATERIALS AND METHODS: Databases including MEDLINE, ISI - Web of Science, PubMed, EMBASE, Scopus, ProQuest, and Science Direct were searched for articles published between 1991 and 2018. The quality of the selected articles wa…

Repeated Chlamydia trachomatis infections are associated with lower bacterial loads.

Chlamydia trachomatis (CT) infections remain highly prevalent. CT reinfection occurs frequently within months after treatment, likely contributing to sustaining the high CT infection prevalence. Sparse studies have suggested CT reinfection is associated with a lower organism load, but it is unclear whether CT load at the time of treatment influences CT reinfection risk. In this study, women presenting for treatment of a positive CT screening test were enrolled, treated and returned for 3- and 6-month follow-up visits. CT organism loads were quantified at each visit. We evaluated for an associa…

Chlamydia trachomatis-induced Fitz-Hugh-Curtis syndrome: a case report.

BACKGROUND: Fitz-Hugh-Curtis syndrome is defined as perihepatitis associated with pelvic inflammatory disease. Chlamydia trachomatis is one of its most common aetiologies. This syndrome usually presents with right upper quadrant abdominal pain mimicking other hepatobiliary and gastrointestinal pathologies, hence, posing a diagnostic dilemma in settings with limited diagnostic tools. CASE REPORT: A 32 year old African female presented with acute right upper quadrant abdominal pain and vaginal discharge, for which she had previously received treatment in another health center with no improvemen…

Chlamidia trachomatis Cellular Exit Alters Взаимодействие с Dendritic Cells.

Стратегии, используемые патогенами для выхода из принимающих клеток, представляют собой область патогенеза, которой удивительно мало внимания, учитывая необходимость этого шага для распространения инфекций. Еще меньше известно о том, как выход через эти пути влияет на взаимодействие хостинг-патоген и формирование иммунной реакции. Хламидия трахоматис выводит эпителиальные клетки с помощью двух одинаково активных механизмов: лиза и экструзия. Исследования характеризуют результаты взаимодействия между врожденными иммунными клетками, такими, как дендритные клетки и макрофаги, и бесплатными внекле

Совпадение в аннотации оригинала
The strategies utilized by pathogens to exit host cells are an area of pathogenesis which has received surprisingly little attention, consid … se pathways affects downstream host-pathogen interactions and the generation of an immune response. Chlamydia trachomatis exits host epithelial cells through two equally active mechanisms: lysis and extrusion. Studies have characterized the outcome of interactions between host innate immune cells, such as dendritic cells and macrophages, and free, extracellular Chlamyd …