Characterization of Pgp3, a<i>Chlamydia trachomatis</i>Plasmid-Encoded Immunodominant Antigen

Chen, Ding; Lei, Lei; Lu, Chunxue; Galaleldeen, Ahmad; Hart, P. John; Zhong, Guangming

doi:10.1128/jb.00847-10

Cited by 74 publications

(77 citation statements)

References 44 publications

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“…In some experiments, the GST-fusion proteins bound to the glutathione-agarose beads were used to absorb the antibodies for confirming the antibody specificities. Production of various control GST-fusion proteins, including GST-CPAF (a chlamydia-secreted serine protease [10]), GST-Pgp3 (a chlamydial plasmid-encoded outer membrane and secretion protein [6,24]), GST-cHSP60 (chlamydial HSP60), and GST-MOMP (the chlamydial major outer membrane protein from serovar D) have been described elsewhere (36).…”

Section: Methodsmentioning

confidence: 99%

Chlamydia trachomatis Secretion of an Immunodominant Hypothetical Protein (CT795) into Host Cell Cytoplasm

Lei

Gong

et al. 2011

J Bacteriol

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The Chlamydia-specific hypothetical protein CT795 was dominantly recognized by human antisera produced during C. trachomatis infection but not by animal antisera raised against dead chlamydia organisms. The immundominant region recognized by the human antibodies was mapped to the N-terminal fragment T22-S69. The endogenous CT795 was detected in the cytoplasm of host cells during C. trachomatis infection and was highly enriched in the host cytosolic fraction but absent in the purified chlamydia organisms, suggesting that CT795 is synthesized and secreted into host cell cytoplasm without incorporation into the organisms. All C. trachomatis serovars tested secreted CT795. A predicted signal peptide of CT795 directed the mature PhoA to cross Escherichia coli inner membranes. The secretion of CT795 in Chlamydia-infected cells was inhibited by a C 16 compound targeting signal peptidase I, but not by a C 1 compound known to block the type III secretion pathway. These results suggest that CT795, like CPAF (a Chlamydia-secreted virulence factor), is secreted into the host cell cytoplasm via a sec-dependent mechanism and not by a type III secretion pathway. The above characterizations of CT795 have provided important information for further understanding the potential roles of CT795 in C. trachomatis pathogenesis.

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Section: Methodsmentioning

confidence: 99%

Chlamydia trachomatis Secretion of an Immunodominant Hypothetical Protein (CT795) into Host Cell Cytoplasm

Lei

Gong

et al. 2011

J Bacteriol

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“…Interestingly, some of the chlamydial antigens that trafficked to the ER were seen to co-localize with the MHC-like molecule CD1d (see below) (Wyrick 2010). Others have shown that proteins such as the chlamydial outer membrane complex protein B (OmcB) (Qi, Gong et al 2011) and the chlamydia protease, CPAF (see below), are present in the host cell cytosol (Sharma, Bosnic et al 2004;Kawana, Quayle et al 2007), the latter being secreted through a Sec-dependent pathway (Chen, Lei et al 2010). C. trachomatis also uses the type III secretory system (T3SS) to move bacterial virulence proteins from EB into the host cytosol (Clifton, Fields et al 2004;Hower, Wolf et al 2009).…”

Section: Pathogen Immune Evasionmentioning

confidence: 99%

Host-Pathogen Co-Evolution: Chlamydia trachomatis Modulates Surface Ligand Expression in Genital Epithelial Cells to Evade Immune Recognition

Caesar¹,

Ibana²,

Schust³

2012

Chlamydia

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Chlamydia 26infectious spill into the female peritoneal cavity. The disease can result in scarring and pelvic organ disfigurement that lead to increases in ectopic pregnancy rates, tubal factor infertility (Hellstrom, Schachter et al. 1987) and possibly early pregnancy wastage (Witkin 1999). If left untreated during pregnancy, chlamydial genital infections in women have been associated with preterm delivery (Rours, Duijts et al. 2011). Developmental cycle of Chlamydia trachomatisChlamydia exhibits a predominantly biphasic developmental cycle, differentiating between a metabolically inactive but infectious elementary body (EB) and a replicating and metabolically active, but non-infectious, reticulate body (RB) (Nelson, Virok et al. 2005;Linhares and Witkin 2010). Attachment and entry of EBs into permissive cells are critical steps in chlamydial development, but the molecules and mechanisms utilized in these processes are not well understood. Several bacterial ligands have been implicated as adhesins, and include heparin sulfate-like proteins, MOMP, OmcB, glycoproteins and Hsp70 (reviewed by Hackstadt 1999). The host factor/s involved in attachment is/are likely proteinacious, and the host cytoplasmic chaperone protein disulfide isomerase (PDI) has been strongly implicated as a structural requirement for attachment of multiple serovars, as well as necessary for entry (Davis, Raulston et al. 2002;Conant and Stephens 2007;Abromaitis and Stephens 2009). After EB internalization, Chlamydia-derived vesicles mature into a specialized parasitophorous vacuole termed an inclusion, which is nonfusogenic with lysosomal and endosomal membranes (Fields, Fischer et al. 2002;Carabeo, Mead et al. 2003;Hybiske and Stephens 2007a;Hybiske and Stephens 2007b). The exact mechanisms involved in the differentiation of the chlamydial EB into a RB remain incompletely described, but morphological investigations have demonstrated decondensation of chromatin occurs early in the process and supports the transition from a metabolically inert EB to a metabolically active RB (Beatty, Byrne, et al. 1993;Beatty, Morrison, et al. 1995;Belland, Zhong et al. 2003) Elegant investigations using transcriptional profiling have listed chaperonin, metabolite translocation, metabolite interconversion, endosomal trafficking, and inclusion membrane modification genes to be among the first to be activated (immediate early genes) during this transition (Belland, Zhong, et al. 2003;AbdelRahman and Belland 2005). As might have been predicted, these genes fall into categories required for pathogen acquisition of nutrients and for inhibiting fusion of the chlamydial inclusion with the host cell lysosomal pathway. Inside the inclusion, the elementary bodies differentiate into reticulate bodies that, in turn, divide rapidly via binary fission. RB condense back into EB and completion of the chlamydial cell cycle results in EB release by host cell lysis or extrusion (Todd and Caldwell 1985; ;Hybiske and Stephens 2007b). Secondary differentiation of RB back into EB invo...

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“…Many virulence factor candidates have been identified, such as the polymorphic outer membrane autotransporter family of proteins [11,12], the putative large cytotoxin [13], stress response proteins [14], and chlamydial secretion effectors [15][16][17]. It is known that C. trachomatis organisms can secrete numerous proteins into host cell cytoplasm [18,19]. Among them, Chlamydial Protease-Like Activity Factor (CPAF), a chlamydial type II secretion protein, may serve as a promising candidate of virulence factor as proposed [16,[20][21][22].…”

Section: Introductionmentioning

confidence: 99%

CPAF selectively degrades chlamydial T cell antigens for inhibiting antigen presentation

Zhang

Zhong

Cai

et al. 2017

J Infect Dev Ctries

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Introduction: Chlamydia trachomatis is the leading cause of sexually transmitted bacterial disease, which may cause significant threats, such as pelvic inflammatory disease and tubal factor infertility, to women if untreated. The pathological mechanisms of chlamydia-induced disease remain largely unknown, but it has been proposed that CPAF, a chlamydia-secreted serine protease, may play major roles in aiding chlamydial infection and contribute to chlamydia pathogenesis during in vivo infection. According to previous results, CPAF targets host immunity by degrading antimicrobial peptides and neutralizing complement activity; however, whether CPAF is involved in chlamydial antigen presentation has never been reported. Methodology: Antigen presentation assay was used to monitor the effects of CPAF on OT1-, OT2-, and chlamydia T cell antigen-mediated antigen presentation. In vitro cell-free degradation assay was used to detect CPAF processing of chlamydia T cell antigens. Results: We found that CPAF preferably inhibits OT2-but not OT1-mediated antigen presentation. CPAF inhibits OT2 antigen presentation by direct proteolytic cleavage in the wild type CPAF, but not enzymatic mutants. Importantly, several previously identified chlamydial T cell antigens were selectively degraded by CPAF when co-incubated in vitro. In addition, specific inhibition T cell antigen presentation by CPAF was correlated with T cell antigen cleavage by CPAF in vitro assay. Conclusions: Our experiments demonstrated that CPAF selectively and specifically degrades chlamydial T cell antigens, which chlamydia may utilize as a novel mechanism for evading host immune responses to promote chlamydia survival.

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Characterization of Pgp3, aChlamydia trachomatisPlasmid-Encoded Immunodominant Antigen

Cited by 74 publications

References 44 publications

Chlamydia trachomatis Secretion of an Immunodominant Hypothetical Protein (CT795) into Host Cell Cytoplasm

Chlamydia trachomatis Secretion of an Immunodominant Hypothetical Protein (CT795) into Host Cell Cytoplasm

Host-Pathogen Co-Evolution: Chlamydia trachomatis Modulates Surface Ligand Expression in Genital Epithelial Cells to Evade Immune Recognition

CPAF selectively degrades chlamydial T cell antigens for inhibiting antigen presentation

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