PmpI antibody reduces the inhibitory effect of Vp1 on Chlamydia trachomatis infectivity

2018 ◽  
Vol 64 (6) ◽  
pp. 376-384 ◽  
Author(s):  
Jie Ren ◽  
Tingting Lian ◽  
Lili Shao ◽  
Yuanjun Liu ◽  
Quanzhong Liu
Keyword(s):  
Chlamydia Trachomatis ◽  
Outer Membrane ◽  
Molecular Mechanisms ◽  
Preliminary Investigation ◽  
Inhibitory Effect ◽  
Antibody Treatment ◽  
Common Cause ◽  
Sexually Transmitted ◽  
Capsid Protein Vp1 ◽  
Far Western Blot

Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infections. The effect of antibiotic treatment is not satisfactory, and there is currently no vaccine to prevent C. trachomatis infection. Our results showed that Chlamydia virus CPG1 capsid protein Vp1 treatment significantly inhibited C. trachomatis growth in cell culture, and the inclusion numbers of different C. trachomatis serotypes were decreased. In addition, we conducted a preliminary investigation of the possible mechanisms behind the Vp1 inhibition effects and the C. trachomatis molecules targeted by Vp1. Using far-western blot and GST pull-down assay, we found that purified Vp1 can bind to the C. trachomatis outer membrane protein PmpI. PmpI polyclonal antibody treatment markedly reduced the inhibitory effect of Vp1 on C. trachomatis infectivity. On the basis of these experimental results, we infer that PmpI participates in the inhibitory effect of Vp1 and may be a potential receptor of Vp1 in the outer membrane of C. trachomatis. Our research provides clues regarding the molecular mechanisms underlying the interactions between chlamydia virus and chlamydia.

scholarly journals Effects ofMentha suaveolensEssential Oil onChlamydia trachomatis

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Rosa Sessa ◽  
Marisa Di Pietro ◽  
Fiorenzo De Santis ◽  
Simone Filardo ◽  
Rino Ragno ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Substantial Reduction ◽  
Developmental Cycle ◽  
Elementary Body ◽  
Promising Candidate ◽  
Common Cause ◽  
Sexually Transmitted ◽  
Reticulate Body ◽  
Preventative Strategy

Chlamydia trachomatis, the most common cause of sexually transmitted bacterial infection worldwide, has a unique biphasic developmental cycle alternating between the infectious elementary body and the replicative reticulate body.C. trachomatisis responsible for severe reproductive complications including pelvic inflammatory disease, ectopic pregnancy, and obstructive infertility. The aim of our study was to evaluate whetherMentha suaveolensessential oil (EOMS) can be considered as a promising candidate for preventingC. trachomatisinfection. Specifically, we investigated thein vitroeffects of EOMS towardsC. trachomatisanalysing the different phases of chlamydial developmental cycle. Our results demonstrated that EOMS was effective towardsC. trachomatis, whereby it not only inactivated infectious elementary bodies but also inhibited chlamydial replication. Our study also revealed the effectiveness of EOMS, in combination with erythromycin, towardsC. trachomatiswith a substantial reduction in the minimum effect dose of antibiotic. In conclusion, EOMS treatment may represent a preventative strategy since it may reduceC. trachomatistransmission in the population and, thereby, reduce the number of new chlamydial infections and risk of developing of severe sequelae.

scholarly journals A Recombinant Chlamydia trachomatis MOMP Vaccine Elicits Cross-serogroup Protection in Mice Against Vaginal Shedding and Infertility

2019 ◽  
Vol 221 (2) ◽  
pp. 191-200 ◽  
Author(s):  
Delia F Tifrea ◽  
Sukumar Pal ◽  
Luis M de la Maza
Keyword(s):  
Chlamydia Trachomatis ◽  
Membrane Protein ◽  
Immune Responses ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Subunit Vaccine ◽  
Bacterial Pathogen ◽  
Male Mice ◽  
Fertility Rates ◽  
Sexually Transmitted

Abstract Background Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen worldwide. Here, we determined the ability of a C. trachomatis recombinant major outer membrane protein (rMOMP) vaccine to elicit cross-serogroup protection. Methods Female C3H/HeN mice were vaccinated by mucosal and systemic routes with C. trachomatis serovar D (UW-3/Cx) rMOMP and challenged in the ovarian bursa with serovars D (UW-3/Cx), D (UCI-96/Cx), E (IOL-43), or F (N.I.1). CpG-1826 and Montanide ISA 720 were used as adjuvants. Results Immune responses following vaccination were more robust against the most closely related serovars. Following a genital challenge (as determined by number of mice with positive vaginal cultures, number of positive cultures, number of inclusion forming units recovered, and number of days with positive cultures) mice challenged with C. trachomatis serovars of the same complex were protected but not those challenged with serovar F (N.I.1) from a different subcomplex. Females were caged with male mice. Based on fertility rates, number of embryos, and hydrosalpinx formation, vaccinated mice were protected against challenges with serovars D (UW-3/Cx), D (UCI-96/Cx), and E (IOL-43) but not F (N.I.1). Conclusions This is the first subunit vaccine shown to protect mice against infection, pathology, and infertility caused by different C. trachomatis serovars.

scholarly journals A Novel Cleavage Pattern of Complement C5 Induced by Chlamydia trachomatis Infection via the Chlamydial Protease CPAF

2022 ◽  
Vol 11 ◽  
Author(s):  
Liang Peng ◽  
Jingping Gao ◽  
Zihao Hu ◽  
Hongbo Zhang ◽  
Lingli Tang ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Serine Protease ◽  
Chlamydial Infection ◽  
Inhibitory Effect ◽  
Cleavage Pattern ◽  
Potential Therapeutic Target ◽  
Chlamydia Trachomatis Infection ◽  
Sexually Transmitted ◽  
Strong Inhibitory Effect ◽  
Nafamostat Mesylate

Urogenital Chlamydia trachomatis infection is one of the most common bacterial sexually transmitted diseases globally. Untreated C. trachomatis infections can ascend to the upper genital tract and establish a series of severe complications. Previous studies using C3−/− and C5−/− mice models demonstrated that C3-independent activation of C5 occurred during C. trachomatis infection. However, the mechanism of how chlamydial infection activates C5 in the absence of C3 has yet to be elucidated. To delineate interactions between C5 and chlamydial infection, cleavage products in a co-incubation system containing purified human C5 and C. trachomatis-HeLa229 cell lysates were analyzed, and a novel cleavage pattern of C5 activation induced by C. trachomatis infection was identified. C5 was cleaved efficiently at the previously unidentified site K970, but was cleaved poorly at site R751. C5b was modified to C5bCt, which later formed C5bCt-9, which had enhanced lytic ability compared with C5b-9. The chlamydial serine protease CPAF contributed to C3-independent C5 activation during C. trachomatis infection. Nafamostat mesylate, a serine protease inhibitor with a good safety profile, had a strong inhibitory effect on C5 activation induced by chlamydial infection. These discoveries reveal the mechanism of C3-independent C5 activation induced by chlamydial infection, and furthermore provide a potential therapeutic target and drug for preventing tubal fibrosis caused by chlamydial infection.

scholarly journals Chlamydia trachomatisLipopolysaccharide Evades the Canonical and Noncanonical Inflammatory Pathways To Subvert Innate Immunity

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Chunfu Yang ◽  
Michael Briones ◽  
Janice Chiou ◽  
Lei Lei ◽  
Michael John Patton ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Chlamydia Trachomatis ◽  
Immune Responses ◽  
Sexually Transmitted Infections ◽  
Outer Membrane ◽  
Content Type ◽  
Sexually Transmitted ◽  
Inflammatory Pathways ◽  
High Incidence ◽  
Potent Agonist

ABSTRACTChlamydia trachomatisis the most common bacterial cause of sexually transmitted infections.C. trachomatissexually transmitted infections are commonly asymptomatic, implying a pathogenic strategy for the evasion of innate inflammatory immune responses, a paradox as theC. trachomatisouter membrane contains lipopolysaccharide (LPS), a known potent agonist of inflammatory innate immunity. Here, we studied the ability of chlamydial LPS to activate the proinflammatory canonical and noncanonical inflammasome pathways in mouse bone marrow-derived macrophages (BMDM). We show, in comparison toEscherichiacoliLPS, thatC. trachomatisLPS-treated BMDM produce significantly less IL-6, TNF, and type I interferon mRNA, indicating that downstream signaling through the canonical TLR4 myddosome and triffosome pathways was blocked. We confirmed this inC. trachomatisLPS-treated BMDM by showing the lack of NF-κB and IRF3 phosphorylation, respectively. Interestingly,C. trachomatisLPS bound CD14 and promoted its endocytosis; however; it did not promote efficient TLR4/MD-2 dimerization or endocytosis, known requirements for myddosome and triffosome signaling pathways. We further found that transfection of BMDM withC. trachomatisLPS did not cause pyroptotic cell ballooning, cytotoxicity, or IL-1β secretion, all characteristic features of noncanonical inflammasome activation. Western blotting confirmed that cytosolicC. trachomatisLPS failed to signal through caspase-11, as shown by the lack of gasdermin D, caspase-1, or IL-1β proteolytic cleavage. We propose that chlamydiae evolved a unique LPS structure as a pathogenic strategy to avoid canonical and noncanonical innate immune signaling and conclude that this strategy might explain the high incidence of asymptomatic infections.IMPORTANCEChlamydia trachomatisis the most common bacterial cause of sexually transmitted infections (STI).C. trachomatisSTI are commonly asymptomatic, implying a pathogenic strategy for the evasion of innate inflammatory immune responses, a paradox as theC. trachomatisouter membrane contains lipopolysaccharide (LPS), a known potent agonist of inflammatory innate immunity. Here, we found thatC. trachomatisLPS is not capable of engaging the canonical TLR4/MD-2 or noncanonical caspase-11 inflammatory pathways. The inability ofC. trachomatisLPS to trigger innate immunity inflammatory pathways is related to its unique fatty acid structure. Evolutionary modification of the LPS structure likely evolved as a pathogenic strategy to silence innate host defense mechanisms. The findings might explain the high incidence of asymptomatic chlamydial genital infection.

Molecular Mechanisms of the Inhibitory Effects of Bupivacaine, Levobupivacaine, and Ropivacaine on Sarcolemmal Adenosine Triphosphate–sensitive Potassium Channels in the Cardiovascular System

2004 ◽  
Vol 101 (2) ◽  
pp. 390-398 ◽  
Author(s):  
Takashi Kawano ◽  
Shuzo Oshita ◽  
Akira Takahashi ◽  
Yasuo Tsutsumi ◽  
Yoshinobu Tomiyama ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Adenosine Triphosphate ◽  
Local Anesthetics ◽  
Molecular Mechanisms ◽  
Transmembrane Domain ◽  
Katp Channels ◽  
Inhibitory Effect ◽  
Amino Acid Residues ◽  
Sulfonylurea Receptor ◽  
Inhibitory Effects

Background Sarcolemmal adenosine triphosphate-sensitive potassium (KATP) channels in the cardiovascular system may be involved in bupivacaine-induced cardiovascular toxicity. The authors investigated the effects of local anesthetics on the activity of reconstituted KATP channels encoded by inwardly rectifying potassium channel (Kir6.0) and sulfonylurea receptor (SUR) subunits. Methods The authors used an inside-out patch clamp configuration to investigate the effects of bupivacaine, levobupivacaine, and ropivacaine on the activity of reconstituted KATP channels expressed in COS-7 cells and containing wild-type, mutant, or chimeric SURs. Results Bupivacaine inhibited the activities of cardiac KATP channels (IC50 = 52 microm) stereoselectively (levobupivacaine, IC50 = 168 microm; ropivacaine, IC50 = 249 microm). Local anesthetics also inhibited the activities of channels formed by the truncated isoform of Kir6.2 (Kir6.2 delta C36) stereoselectively. Mutations in the cytosolic end of the second transmembrane domain of Kir6.2 markedly decreased both the local anesthetics' affinity and stereoselectivity. The local anesthetics blocked cardiac KATP channels with approximately eightfold higher potency than vascular KATP channels; the potency depended on the SUR subtype. The 42 amino acid residues at the C-terminal tail of SUR2A, but not SUR1 or SUR2B, enhanced the inhibitory effect of bupivacaine on the Kir6.0 subunit. Conclusions Inhibitory effects of local anesthetics on KATP channels in the cardiovascular system are (1) stereoselective: bupivacaine was more potent than levobupivacaine and ropivacaine; and (2) tissue specific: local anesthetics blocked cardiac KATP channels more potently than vascular KATP channels, via the intracellular pore mouth of the Kir6.0 subunit and the 42 amino acids at the C-terminal tail of the SUR2A subunit, respectively.

scholarly journals Prevalence of urogenital, anal, and pharyngeal infections with Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium: a cross-sectional study in Reunion island

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. Calas ◽  
N. Zemali ◽  
G. Camuset ◽  
J. Jaubert ◽  
R. Manaquin ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Neisseria Gonorrhoeae ◽  
Mycoplasma Genitalium ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Transmitted Infection ◽  
Cross Sectional ◽  
Sexually Transmitted ◽  
Urogenital Infection ◽  
High Prevalence

Abstract Background Recommendations for sexually transmitted infection (STI) screening vary significantly across countries. This study evaluated the prevalence of urogenital and extragenital infections with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG) in patients visiting a French STI clinic in the Indian Ocean region to determine whether current STI screening practices should be updated. Methods This cross-sectional study examined all patients who visited the STI clinic between 2014 and 2015. Triplex polymerase chain reaction screening for CT, NG, and MG was performed on urine, vaginal, pharyngeal, and anal specimens (FTD Urethritis Basic Kit, Fast Track Diagnostics, Luxembourg). Results Of the 851 patients enrolled in the study, 367 were women (367/851, 43.2%) and 484 were men (484/851, 56.0%). Overall, 826 urogenital specimens (826/851, 97.1%), 606 pharyngeal specimens (606/851, 71.2%), and 127 anal specimens (127/851, 14.9%) were taken from enrolled patients. The prevalence of urogenital CT and MG was high in women ≤25 years (19/186, 10.21%; 5/186, 2.69%) and in men who have sex with women ≤30 years (16/212, 7.54%; 5/212, 2.36%). Among patients with urogenital CT infection, 13.7% (7/51) had urethritis. All patients with urogenital MG infection were asymptomatic. Men who have sex with men had a high prevalence of pharyngeal CT (2/45, 4.44%) and NG (3/44, 6.81%) and a high prevalence of anal CT (2/27, 7.41%), NG (2/27, 7.40%), and MG (1/27, 3.70%). After excluding patients with concomitant urogenital infection, extragenital infections with at least 1 of the 3 pathogens were found in 20 swabs (20/91, 21.9%) taken from 16 patients (16/81, 19.7%), all of them asymptomatic. Conclusions Routine multisite screening for CT, NG, and MG should be performed to mitigate the transmission of STIs in high-risk sexually active populations.

scholarly journals The Inhibitory Effect of a Novel Polypeptide Fraction fromArca subcrenataon Cancer-Related Inflammation in Human Cervical Cancer HeLa Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yu Wu ◽  
Xianjing Hu ◽  
Liyan Song ◽  
Jianhua Zhu ◽  
Rongmin Yu
Keyword(s):  
Cervical Cancer ◽  
Hela Cells ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Basic Research ◽  
Inhibitory Effect ◽  
Fishery Resource ◽  
Proinflammatory Mediators ◽  
Raw264.7 Macrophage ◽  
Human Cervical Cancer

Inflammation is known to be closely associated with the development of cancer. The study was launched in human cervical cancer HeLa cells to investigate the antitumor and anti-inflammatory effects of P2, a marine polypeptide fraction from an important fishery resourceArca subcrenata. The basic research showed that P2 could suppress the production of nitric oxide in LPS-induced RAW264.7 macrophage cells as well as the secretion of inflammatory cytokines IL-6 and TNF-αin human cervical cancer HeLa cells. For the molecular mechanisms, P2 was shown to downregulate the gene expression of proinflammatory cytokines IL-6 and IL-8 and to inhibit the COX-2 and iNOS-related pathways in HeLa cells. In consequence, P2 might inhibit tumor development by blocking the interaction between tumor microenvironment and proinflammatory mediators. All findings indicate that P2 possesses the potential to be developed as a novel agent for cancer therapy.

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