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.

CT135 mediates the resistance of to primate interferon gamma stimulated immune defenses.

Evading host innate immune defenses is a critical feature of infections, and the mechanisms used by to subvert these pathways are incompletely understood. We screened a library of chimeric mutants for genetic factors important for interference with cell-autonomous immune defenses. Mutant strains with predicted truncations of the inclusion membrane protein CT135 were susceptible to interferon gamma-activated immunity in human cells.

Antibodies from chlamydia-infected individuals facilitate phagocytosis via Fc receptors.

Non-neutralizing functions of antibodies, including phagocytosis, may play a role in (CT) infection, but these functions have not been studied and assays are lacking. We utilized a flow-cytometry-based assay to determine whether serum samples from a well-characterized cohort of CT-infected and naïve control individuals enhanced phagocytosis via Fc-receptor-expressing THP-1 cells, and whether this activity correlated with antibody titers. Fc-receptor-mediated phagocytosis was detected only in CT+ donors.

Genomic Analysis of MSM Rectal Chlamydia trachomatis Isolates Identifies Predicted Tissue-Tropic Lineages Generated by Intraspecies Lateral Gene Transfer-Mediated Evolution.

Chlamydia trachomatis is an obligate intracellular bacterium that causes serious diseases in humans. Rectal infection and disease caused by this pathogen are important yet understudied aspects of C. trachomatis natural history.

Crystal structure of an inorganic pyrophosphatase from Chlamydia trachomatis D/UW-3/Cx.

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections globally and is one of the most commonly reported infections in the United States. There is a need to develop new therapeutics due to drug resistance and the failure of current treatments to clear persistent infections. Structures of potential C.

A broad-spectrum cloning vector that exists as both an integrated element and a free plasmid in Chlamydia trachomatis.

Plasmid transformation of chlamydiae has created new opportunities to investigate host-microbe interactions during chlamydial infections; however, there are still limitations. Plasmid transformation requires a replicon derived from the native Chlamydia plasmid, and these transformations are species-specific. We explored the utility of a broad host-range plasmid, pBBR1MCS-4, to transform chlamydiae, with a goal of simplifying the transformation process.

Inter-species lateral gene transfer focused on the Chlamydia plasticity zone identifies loci associated with immediate cytotoxicity and inclusion stability.

Chlamydia muridarum actively grows in murine mucosae and is a representative model of human chlamydial genital tract disease. In contrast, C. trachomatis infections in mice are limited and rarely cause disease.

Priorities for sexually transmitted infection vaccine research and development: Results from a survey of global leaders and representatives.

Objective: To determine the sexually transmitted infection (STI) vaccine research priorities of global leaders in STI vaccine research, development, and service provision.

Methods: Global representatives attending the symposium preceding the STI & HIV World Congress in 2019 were invited to complete an electronic survey. We asked participants to rank items by importance/priority for STI vaccine development for the following areas of focus: specific STIs (gonorrhea, chlamydia, syphilis, herpes, and trichomoniasis), broad research domains (basic science, funding, communication, program planning, and vaccine hesitancy), and specific research activities related to these domains.

Wikidata as a knowledge graph for the life sciences.

Wikidata is a community-maintained knowledge base that has been assembled from repositories in the fields of genomics, proteomics, genetic variants, pathways, chemical compounds, and diseases, and that adheres to the FAIR principles of findability, accessibility, interoperability and reusability. Here we describe the breadth and depth of the biomedical knowledge contained within Wikidata, and discuss the open-source tools we have built to add information to Wikidata and to synchronize it with source databases. We also demonstrate several use cases for Wikidata, including the crowdsourced curation of biomedical ontologies, phenotype-based diagnosis of disease, and drug repurposing.

Chromosomal Recombination Targets in Interspecies Lateral Gene Transfer.

Lateral gene transfer (LGT) among strains is common, in both isolates generated in the laboratory and those examined directly from patients. In contrast, there are very few examples of recent acquisition of DNA by any spp. from any other species.

Development of Transposon Mutagenesis for Chlamydia muridarum.

Functional genetic analysis of has been a challenge due to the historical genetic intractability of , although recent advances in chlamydial genetic manipulation have begun to remove these barriers. Here, we report the development of the Himar C9 transposon system for , a mouse-adapted species that is widely used in infection models. We demonstrate the generation and characterization of an initial library of 33 chloramphenicol (Cam)-resistant, green fluorescent protein (GFP)-expressing transposon mutants.

The Extrusion Exit Mechanism Is Regulated by Host Abscission Proteins.

The cellular exit strategies of intracellular pathogens have a direct impact on microbial dissemination, transmission, and engagement of immune responses of the host. exit their host via a budding mechanism called extrusion, which offers protective benefits to as they navigate their extracellular environment. Many intracellular pathogens co-opt cellular abscission machinery to facilitate cell exit, which is utilized to perform scission of two newly formed daughter cells following mitosis.

Proximity-dependent proteomics of the Chlamydia trachomatis inclusion membrane reveals functional interactions with endoplasmic reticulum exit sites.

Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection, responsible for millions of infections each year. Despite this high prevalence, the elucidation of the molecular mechanisms of Chlamydia pathogenesis has been difficult due to limitations in genetic tools and its intracellular developmental cycle. Within a host epithelial cell, chlamydiae replicate within a vacuole called the inclusion.

Recurrent/Intermittent Vaginal and Rectal Chlamydial Infection Following Treatment: A Prospective Cohort Study Among Female Sexually Transmitted Disease Clinic Patients.

Background: Rectal Chlamydia trachomatis (CT) is common among clinic-attending women, but little is known about clearance and health implications of rectal CT.

Methods: At the municipal sexually transmitted disease clinic in Seattle, Washington, in 2017-2018, we enrolled women at high risk for urogenital CT into an 8-week prospective study. Women received standard CT treatment at enrollment.

Direct visualization of the expression and localization of chlamydial effector proteins within infected host cells.

Chlamydia secrete into host cells a diverse array of effector proteins, but progress in characterizing the spatiotemporal localization of these proteins has been hindered by a paucity of genetic approaches in Chlamydia and also by the challenge of studying these proteins within the live cellular environment. We adapted a split-green fluorescent protein (GFP) system for use in Chlamydia to label chlamydial effector proteins and track their localization in host cells under native environment. The efficacy of this system was demonstrated by detecting several known Chlamydia proteins including IncA, CT005 and CT694.

Orchestration of the mammalian host cell glucose transporter proteins-1 and 3 by Chlamydia contributes to intracellular growth and infectivity.

Chlamydia are gram-negative obligate intracellular bacteria that replicate within a discrete cellular vacuole, called an inclusion. Although it is known that Chlamydia require essential nutrients from host cells to support their intracellular growth, the molecular mechanisms for acquiring these macromolecules remain uncharacterized. In the present study, it was found that the expression of mammalian cell glucose transporter proteins 1 (GLUT1) and glucose transporter proteins 3 (GLUT3) were up-regulated during chlamydial infection.

Sensing of Bacterial Cyclic Dinucleotides by the Oxidoreductase RECON Promotes NF-κB Activation and Shapes a Proinflammatory Antibacterial State.

Bacterial and host cyclic dinucleotides (cdNs) mediate cytosolic immune responses through the STING signaling pathway, although evidence suggests that alternative pathways exist. We used cdN-conjugated beads to biochemically isolate host receptors for bacterial cdNs, and we identified the oxidoreductase RECON. High-affinity cdN binding inhibited RECON enzyme activity by simultaneously blocking the substrate and cosubstrate sites, as revealed by structural analyses.

Chlamydia trachomatis Cellular Exit Alters Interactions with Host Dendritic Cells.

The strategies utilized by pathogens to exit host cells are an area of pathogenesis which has received surprisingly little attention, considering the necessity of this step for infections to propagate. Even less is known about how exit through these pathways affects downstream host-pathogen interactions and the generation of an immune response. exits host epithelial cells through two equally active mechanisms: lysis and extrusion.

Extrusions are phagocytosed and promote Chlamydia survival within macrophages.

The precise strategies that intracellular pathogens use to exit host cells have a direct impact on their ability to disseminate within a host, transmit to new hosts, and engage or avoid immune responses. The obligate intracellular bacterium Chlamydia trachomatis exits the host cell by two distinct exit strategies, lysis and extrusion. The defining characteristics of extrusions, and advantages gained by Chlamydia within this unique double-membrane structure, are not well understood.