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      Chlamydia trachomatis Growth and Cytokine mRNA Response in a Prostate Cancer Cell Line

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          In the present paper, we report that C. trachomatis can be efficiently propagated and affect mRNA expression for two major cytokines, relevant to tumor progression, in CWR-R1 cells, a malignant prostate cell line. CWR-R1 and McCoy cells, a classic cell line for chlamydial research, were grown and infected with C. trachomatis under similar conditions. Cell monolayers were harvested for RNA analysis and immunostaining with major outer membrane protein (MOMP) antibody at 24, 48, and 72 hours of the postinfection (hpi) period. It was shown that the infectious cycle of chlamydial pathogen in CWR-R1 cells resembles the progression of C. trachomatis infection in McCoy cells but with a few important differences. First of all, the initial stage of C. trachomatis propagation in CWR-R1 cells (24 hpi) was characterized by larger inclusion bodies and more intense, specific immunofluorescent staining of infected cells as compared with McCoy cells. Moreover, there was a corresponding increase in infective progeny formation in CWR-R1 cells along with mRNA for EUO, a crucial gene controlling the early phase of the chlamydial development cycle (24 hpi). These changes were more minimal and became statistically insignificant at a later time point in the infectious cycle (48 hpi). Altogether, these data suggest that the early phase of C. trachomatis infection in CWR-R1 cells is accompanied by more efficient propagation of the pathogen as compared with the growth of C. trachomatis in McCoy cells. Furthermore, propagation of C. trachomatis in CWR-R1 cells leads to enhanced transcription of interleukin-6 and fibroblast growth factor-2, genes encoding two important proinflammatory cytokines implicated in the molecular mechanisms of chemoresistance of prostate cancer and its ability to metastasize. The possible roles of reactive oxygen species and impaired mitochondrial oxidation in the prostate cancer cell line are discussed as factors promoting the early stages of C. trachomatis growth in CWR-R1 cells.

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          Most cited references 32

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          Chlamydia cell biology and pathogenesis.

          Chlamydia spp. are important causes of human disease for which no effective vaccine exists. These obligate intracellular pathogens replicate in a specialized membrane compartment and use a large arsenal of secreted effectors to survive in the hostile intracellular environment of the host. In this Review, we summarize the progress in decoding the interactions between Chlamydia spp. and their hosts that has been made possible by recent technological advances in chlamydial proteomics and genetics. The field is now poised to decipher the molecular mechanisms that underlie the intimate interactions between Chlamydia spp. and their hosts, which will open up many exciting avenues of research for these medically important pathogens.
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            Enhancement of reactive oxygen species production and chlamydial infection by the mitochondrial Nod-like family member NLRX1.

            Chlamydia trachomatis infections cause severe and irreversible damage that can lead to infertility and blindness in both males and females. Following infection of epithelial cells, Chlamydia induces production of reactive oxygen species (ROS). Unconventionally, Chlamydiae use ROS to their advantage by activating caspase-1, which contributes to chlamydial growth. NLRX1, a member of the Nod-like receptor family that translocates to the mitochondria, can augment ROS production from the mitochondria following Shigella flexneri infections. However, in general, ROS can also be produced by membrane-bound NADPH oxidases. Given the importance of ROS-induced caspase-1 activation in growth of the chlamydial vacuole, we investigated the sources of ROS production in epithelial cells following infection with C. trachomatis. In this study, we provide evidence that basal levels of ROS are generated during chlamydial infection by NADPH oxidase, but ROS levels, regardless of their source, are enhanced by an NLRX1-dependent mechanism. Significantly, the presence of NLRX1 is required for optimal chlamydial growth.
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              Evolution, phylogeny, and molecular epidemiology of Chlamydia.

              The Chlamydiaceae are a family of obligate intracellular bacteria characterized by a unique biphasic developmental cycle. It encompasses the single genus Chlamydia, which involves nine species that affect a wide range of vertebral hosts, causing infections with serious impact on human health (mainly due to Chlamydia trachomatis infections) and on farming and veterinary industries. It is believed that Chlamydiales originated ∼700mya, whereas C. trachomatis likely split from the other Chlamydiaceae during the last 6mya. This corresponds to the emergence of modern human lineages, with the first descriptions of chlamydial infections as ancient as four millennia. Chlamydiaceae have undergone a massive genome reduction, on behalf of the deletional bias "use it or lose it", stabilizing at 1-1.2Mb and keeping a striking genome synteny. Their phylogeny reveals species segregation according to biological properties, with huge differences in terms of host range, tissue tropism, and disease outcomes. Genome differences rely on the occurrence of mutations in the >700 orthologous genes, as well as on events of recombination, gene loss, inversion, and paralogous expansion, affecting both a hypervariable region named the plasticity zone, and genes essentially encoding polymorphic and transmembrane head membrane proteins, type III secretion effectors and some metabolic pathways. Procedures for molecular typing are still not consensual but have allowed the knowledge of molecular epidemiology patterns for some species as well as the identification of outbreaks and emergence of successful clones for C. trachomatis. This manuscript intends to provide a comprehensive review on the evolution, phylogeny, and molecular epidemiology of Chlamydia. Copyright © 2014 Elsevier B.V. All rights reserved.

                Author and article information

                Adv Urol
                Adv Urol
                Advances in Urology
                17 January 2019
                : 2019
                1Lycotec Ltd., Granta Park, Cambridge CB21 6GP, UK
                2Department of Medical Microbiology, Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health, 18 Gamaleya Str, Moscow 123098, Russia
                Author notes

                Academic Editor: Kostis Gyftopoulos

                Copyright © 2019 Ivan M. Petyaev et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funded by: Lycotec Ltd.
                Funded by: Gamaleya National Research Center of Epidemiology and Microbiology
                Research Article



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