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Disruption of Chlamydia trachomatis Essential Genes Using DOPE (Dependence on Plasmid-Mediated Expression).

We describe in detail an experimental strategy, DOPE (Dependence On Plasmid-mediated Expression), to enable disruption of an essential chlamydial gene. A wild-type Chlamydia trachomatis strain is first transformed with a β-lactamase-selectable plasmid carrying a copy of the gene under the inducible control of an anhydrotetracycline (ATC)-responsive promoter. Transformants are selected under permissive conditions in the absence of ATC to establish stable plasmid maintenance. The resulting chlamydiae are subsequently transformed with a suicide plasmid encoding a group II intron engineered to tar…

Chlamydia trachomatis inhibits NF-κB-dependent ferroptosis through PARP10 upregulation to promote reproduction.

UNLABELLED: Chlamydia trachomatis (Ct), an obligate intracellular pathogen, manipulates host cell death pathways to establish infection. Although ferroptosis-an iron-dependent cell death process marked by lipid peroxidation-constitutes an antimicrobial defense mechanism, its regulation during Ct infection remains in the early stages of exploration. Here, we report that Ct actively suppresses ferroptosis in host cells, with maximal inhibition at 24 hours post-infection. This suppression was demonstrated through attenuated malondialdehyde production, reduced Fe²+ accumulation, and preserved mito…

Epidemiology of Chlamydia trachomatis in Canada: systematic review and meta-analysis, 1981-2025.

BACKGROUND: This study aimed to systematically review and synthesize evidence on Chlamydia trachomatis prevalence in Canada, describe epidemiological patterns across populations and anatomical sites, and assess associations with prevalence. METHODS: A systematic review of Chlamydia trachomatis prevalence studies was conducted and reported according to PRISMA guidelines. Random-effects meta-analyses generated pooled mean prevalence estimates, and meta-regression analyses explored epidemiological and methodological predictors of prevalence variation. RESULTS: A total of 169 publications were i…

A new core-genome MLST approach for Chlamydia trachomatis genomic surveillance and research.

Chlamydia trachomatis causes common sexually transmitted infections. The use of whole-genome sequencing for its classification and surveillance is limited due to technical challenges and the lack of standardized typing frameworks. In particular, core-genome multilocus sequence typing (cgMLST), a scalable and portable approach widely applied to other bacterial pathogens, remains little explored for C. trachomatis. Here, we compiled and curated a diverse C. trachomatis genome dataset (1230 samples from 26 countries), including publicly available and newly generated assemblies, to develop a cgMLS…

Altering the redox status of Chlamydia trachomatis directly impacts its developmental cycle progression.

Chlamydia trachomatis is an obligate intracellular bacterial pathogen with a unique developmental cycle. It differentiates between two functional and morphological forms: the elementary body (EB) and the reticulate body (RB). The signals that trigger differentiation from one form to the other are unknown. EBs and RBs have distinctive characteristics that distinguish them, including their size, infectivity, proteome, and transcriptome. Intriguingly, they also differ in their overall redox status as EBs are oxidized and RBs are reduced. We hypothesize that alterations in redox may serve as a tri…

Chlamydia trachomatis subverts neutrophil cell death pathways through RIP3 and Mcl-1 manipulation.

Chlamydia trachomatis, an obligate intracellular pathogen, manipulates host cells to evade immune detection, contributing to sexually transmitted diseases with severe complications. Neutrophils, short-lived effector cells, form the first line of innate immune defense against infection. Here, we demonstrate that Chlamydia infection extends the lifespan of human neutrophils, creating a cellular niche for its own survival. Lifespan extension involves the neutrophil PI3K/Akt- and the NF-κB signaling pathways. In addition, infection activates the necroptotic effector receptor-interacting protein ki…

The SWIB domain-containing DNA topoisomerase I of Chlamydia trachomatis mediates DNA relaxation.

Chlamydia trachomatis has a DNA topoisomerase I with a unique C-terminal domain (CTD) homologous to eukaryotic SWIB domains. This study focused on determining the function of the SWIB domain-containing TopA from C. trachomatis (CtTopA). We demonstrated that, despite the lack of sequence similarity at the CTDs between CtTopA and TopA from Escherichia coli (EcTopA), full-length CtTopA removed negative DNA supercoils in vitro and complemented the growth defect of a topA mutant of E. coli. CtTopA is less processive in DNA relaxation than EcTopA in dose-response and time course studies. An antibody…

Trends in Chlamydia trachomatis Treatment Prescribing Practices in King County, Washington, 2010-2018.

BACKGROUND: In 2021, national Chlamydia trachomatis (CT) treatment guidelines changed from recommending either azithromycin (1 g; single dose) or doxycycline (100 mg twice daily for 7 days) to recommending only doxycycline as first-line treatment. The distribution and trends in CT prescribing practices before the guidelines change is largely unknown. METHODS: We conducted a trends analysis using Washington STD surveillance data. We included all female cases of urogenital CT 15 years or older who resided in King County and were diagnosed between 2010 and 2018. Surveillance data included inform…

Recognition of Chlamydia trachomatis by Toll-Like Receptor 9 is altered during persistence.

Toll-like receptor 9 (TLR9) is an innate immune receptor that localizes to endosomes in antigen presenting cells and recognizes single stranded unmethylated CpG sites on bacterial genomic DNA. Previous bioinformatic studies have indicated that the genome of the human pathogen Chlamydia trachomatis contains TLR9 stimulatory motifs, and correlative studies have implied a link between human TLR9 (hTLR9) genotype variants and susceptibility to infection. Here we present our evaluation of the stimulatory potential of C. trachomatis gDNA and its recognition by hTLR9- and murine TLR9 (mTLR9)-expressi…

A TriAdj-Adjuvanted Chlamydia trachomatis CPAF Protein Vaccine Is Highly Immunogenic in Pigs.

Chlamydia trachomatis (Ct) infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs, as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we used the pig model to develop a vaccine candidate against Ct. The vaccine can…

Vitamin D effects on Chlamydia trachomatis infection: a case-control and experimental study.

INTRODUCTION: Vitamin D deficiency is the most common nutritional deficiency worldwide. Chronic vitamin D deficiency causes immune system dysfunction, which increases susceptibility to pathogens such as bacteria, especially intracellular parasites, and viruses. Chlamydia trachomatis (C. t) is an obligate intracellular parasitic bacterium that causes a variety of sequelae. We speculated that vitamin D might be associated with C. t infection. This study aimed to address this gap in knowledge by investigating the relationship between vitamin D and C. t infection using both in vitro and in vivo mo…

Chlamydia trachomatis upregulates lncRNA CYTOR to mediate autophagy through miR-206/MAPK1 axis.

Chlamydia trachomatis infection can be regulated by autophagy-related genes. LncRNA CYTOR has been proven to be involved in autophagy. In this research, we investigated the role of CYTOR in autophagy induced by C. trachomatis and the potential mechanisms. After C. trachomatis infection, CYTOR and MAPK1 were up-regulated and miR-206 was down-regulated, meanwhile, the autophagy-related protein Beclin1 and LC3-Ⅱ/LC3-Ⅰ ratio were increased. Interference with CYTOR or overexpression with miR-206 downregulated the autophagy-related protein Beclin1 and the number of autophagic spots LC3, decreased th…

Recognition of Chlamydia trachomatis by Toll-like receptor 9 is altered during persistence.

Toll-like receptor 9 (TLR9) is an innate immune receptor that localizes to endosomes in antigen presenting cells and recognizes single stranded unmethylated CpG sites on bacterial genomic DNA (gDNA). Previous bioinformatic studies have demonstrated that the genome of the human pathogen Chlamydia trachomatis contains TLR9 stimulatory motifs, and correlative studies have implied a link between human TLR9 (hTLR9) genotype variants and susceptibility to infection. Here, we present our evaluation of the stimulatory potential of C. trachomatis gDNA and its recognition by hTLR9- and murine TLR9 (mTLR…

Chlamydia trachomatis Seroassays Used in Epidemiologic Research: A Narrative Review and Practical Considerations.

Chlamydia trachomatis (CT) is a sexually transmitted infection that can lead to adverse reproductive health outcomes. CT prevalence estimates are primarily derived from screening using nucleic acid amplification tests (NAATs). However, screening guidelines in the United States only include particular subpopulations, and NAATs only detect current infections. In contrast, seroassays identify past CT infections, which is important for understanding the public health impacts of CT, including pelvic inflammatory disease and tubal factor infertility. Older seroassays have been plagued by low sensiti…

Intradermal administration of novel particulate Chlamydia trachomatis vaccine candidates drives protective immune responses.

Chlamydia trachomatis causes the most prevalent bacterial sexually transmitted infection worldwide. Its complex lifecycle and the lack of appropriate antigen delivery vehicles make it difficult to develop an effective C. trachomatis vaccine. Recently, bacterial protein bodies (PBs) have emerged as promising bioparticles for vaccine antigen delivery. By developing a PB-tag for translational fusion, we were able to induce the aggregation of recombinant antigens expressed in Escherichia coli into PBs. Here, we investigated the immunogenicity and efficacy of PBs containing either the C. trachomati…

Altering the redox status of Chlamydia trachomatis directly impacts its developmental cycle progression.

Chlamydia trachomatis is an obligate intracellular bacterial pathogen with a unique developmental cycle. It differentiates between two functional and morphological forms: elementary body (EB) and reticulate body (RB). The signals that trigger differentiation from one form to the other are unknown. EBs and RBs have distinctive characteristics that distinguish them, including their size, infectivity, proteome, and transcriptome. Intriguingly, they also differ in their overall redox status as EBs are oxidized and RBs are reduced. We hypothesize that alterations in redox may serve as a trigger for…

Chlamidia trachomatis TmeA способствует формированию пьедесталов посредством взаимодействия N-WASP и TOCA-1.

Chlamidia trachomatis (C.t.) является причиной нескольких заболеваний человека, включая хламидию, передающуюся половым путем, и трахому глазной инфекции. Как обязательный внутриклеточный патоген бактерий, вторжение имеет существенно важное значение для установления инфекции и последующего патогенеза. Чтобы облегчить вторжение, C.t скрывает белки с помощью своей системы разделения типа III (T3SS). Эти эффекторы облегчают проникновение бактерий, манипулируя несколькими путями регулирования цитоскелета. Предыдущие исследования показали, что белковый белок T3SS имеет решающее значение для вторжени

Совпадение в аннотации оригинала
Chlamydia trachomatis (C.t.) is the causative agent of several human diseases, including the sexually transmitted infection chlamydia and eye infection trachoma. As an obligate intracellular bacterial pathogen, invasion is essential for establishing infection and subsequent pathogenesis. To facilitate invasion, C.t. secretes effector proteins through its typ…

Virulence Protein Pgp3 Is Insufficient To Mediate Plasmid-Dependent Infectivity of Chlamydia trachomatis.

Chlamydia trachomatis is the most common cause of infectious blindness and sexually transmitted bacterial infection globally. C. trachomatis contains a conserved chlamydial plasmid with eight coding sequences. Plasmid-cured Chlamydia strains are attenuated and display reduced infectivity in cell culture and in vivo genital infection of female mice. Mutants that do not express the plasmid-encoded proteins Pgp3, a secreted protein with unknown function, or Pgp4, a putative regulator of pgp3 and other chromosomal loci, display an infectivity defect similar to plasmid-deficient strains. Our object…

Объединение функционального супероксидного генома полиморфизма с хламидией трахоматисом, связанным с периодическим спонтанным абортом.

Окисляющий стресс, вызванный хламидией трахоматисом, связан с такими репродуктивными осложнениями, как повторный спонтанный аборт. Цель перспективного исследования заключалась в оценке того, связаны ли однородные нуклеотидные полиморфизмы (СНП) SOD1 и SOD2 гены C. trachomatis-инфицированные периодические спонтанные аборты (RSA). МЕТОДЫ: 150 пациентов, имеющих опыт работы в АСР, и 150 пациентов, имеющих опыт успешного родовспоможения, были набраны в отделении акушерства и гинекологии больницы " Сафдарджунг " в Дели, Индия. Были собраны образцы мокрой и негепаринизированной крови, и в

Совпадение в аннотации оригинала
BACKGROUND: Oxidative stress generated by Chlamydia trachomatis infection is associated with reproductive complications such as recurrent spontaneous abortion. Aim of prospective study was to evaluate whether single nucleotide polymorphisms (SNPs) of SOD1 and SOD2 gene are associated with C. trachomatis-infected recurrent spontaneous abortion (RSA). METHODS…

Chlamydia trachomatis TmeB antagonizes actin polymerization via direct interference with Arp2/3 activity.

Chlamydia trachomatis is an obligate intracellular pathogen that actively promotes invasion of epithelial cells. A virulence-associated type III secretion system contributes to chlamydial entry and at least four effectors have been described that are deployed during this time. Two of these invasion-related effectors, the translocated membrane-associated effectors A and B (TmeA and TmeB), are encoded in a bi-cistronic operon. TmeA directly activates host N-WASP to stimulate Arp2/3-dependent actin polymerization. According to current working models, TmeA-mediated N-WASP activation contributes to…