Immunoperoxidase Labeling Demonstrates an Early Divergence of Chlamydia Trachomatis from the Endosomal-Lysosomal Pathway

1998 ◽  
Vol 4 (S2) ◽  
pp. 1032-1033
Author(s):  
Elizabeth R. Fischer ◽  
Marci A. Scidmore-Carlson ◽  
Ted Hackstadt

Chlamydia trachomatis is responsible for several significant human diseases including trachoma, the primary source of preventable blindness in developing countries, and is the most common cause of sexually transmitted disease. C. trachomatis is an obligate intracellular prokaryote (ICP) relying on eukaryotic host cells for growth and replication. Typically, microorganisms engulfed by host cells, are trafficked through maturing endosomes to the lysosomal pathway and ultimately destroyed. Survival in a host cell requires the invading organism to either adapt or modify their host environment to avoid fusion with lysosomal vesicles. Organisms such as Mycobacterium tuberculosis have evolved mechanisms to arrest maturation of the endosomes, such that they avoid lysosomal fusion.3 C trachomatis has developed alternative strategies for successful intracellular survival and growth.C. trachomatis exists in two morphologically and functionally distinct forms which multiply in vacuoles termed inclusions. A small dense form known as the elementary body (EB), is the stable extracellular stage of the life cycle capable of attachment and entry into host cells.

2007 ◽  
Vol 190 (5) ◽  
pp. 1605-1614 ◽  
Author(s):  
Robert DeMars ◽  
Jason Weinfurter

ABSTRACT The high frequency of between-strain genetic recombinants of Chlamydia trachomatis among isolates obtained from human sexually transmitted infections suggests that lateral gene transfer (LGT) is an important means by which C. trachomatis generates variants that have enhanced relative fitness. A mechanism for LGT in C. trachomatis has not been described, and investigation of this phenomenon by experimentation has been hampered by the obligate intracellular development of this pathogen. We describe here experiments that readily detected LGT between strains of C. trachomatis in vitro. Host cells were simultaneously infected with an ofloxacin-resistant (Ofxr) mutant of a serovar L1 strain (L1:Ofxr-1) and a rifampin-resistant (Rifr) mutant of a serovar D strain (D:Rifr-1). Development occurred in the absence of antibiotics, and the progeny were subjected to selection for Ofxr Rifr recombinants. The parental strains differed at many polymorphic nucleotide sites, and DNA sequencing was used to map genetic crossovers and to determine the parental sources of DNA segments in 14 recombinants. Depending on the assumed DNA donor, the estimated minimal length of the transferred DNA was ≥123 kb in one recombinant but was ≥336 to ≥790 kb in all other recombinants. Such trans-DNA lengths have been associated only with conjugation in known microbial LGT systems, but natural DNA transformation remains a conceivable mechanism. LGT studies can now be performed with diverse combinations of C. trachomatis strains, and they could have evolutionary interest and yield useful recombinants for functional analysis of allelic differences between strains.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S220-S220
Author(s):  
Gloria E Anyalechi ◽  
Damien Danavall ◽  
Brian H Raphael ◽  
Katherine E Bowden ◽  
Jaeyoung Hong ◽  
...  

Abstract Background Chlamydia trachomatis (CT) causes pelvic inflammatory disease (PID) and other sequelae; however, these associations are not fully characterized. CT serologic assays including Pgp3 ELISA may detect prior CT infection and may better elucidate these associations. We used a serologic Pgp3 multiplex bead array assay (Pgp3MBA) to measure CT seroprevalence in reproductive-age US women and assess the association with PID. Methods We performed CT Pgp3MBA on sera collected from women 18–39 years old during the 2013–2016 cycles of the National Health and Nutrition Examination Survey (NHANES) who had available urine CT nucleic acid amplification test results. Weighted Pgp3MBA CT seroprevalence and 95% confidence intervals (95% CI) were calculated. We also determined weighted prevalence ratios (PRs) and 95% CIs of self-reported lifetime PID among women with and without detectable Pgp3MBA and other characteristics to estimate these US national statistics. Results Among 2,339 women, 1,725 (73.7%) had available sera. Of these women, 1,425 (or 93.4% of those with data) were sexually experienced and had a CT seroprevalence of 35.9% (95% CI 33.4–38.4). When weighted for US women, CT seroprevalence was 30.5% (95% CI 26.6–34.4%), ranging from 16.9% (95% CI 11.0–22.8%) among non-Hispanic Asian women to 70.2% (95% CI 62.4–78.0%) among non-Hispanic black women. PID was reported by 4.2% (95% CI 3.1–5.2) of 1,413 sexually-experienced women with PID data or an estimated 3.8% (95% CI 2.6–5.0) of US women. Among US women, estimated PID varied by Pgp3MBA status; 7.3% (95% CI 4.3–10.2) of Pgp3MBA-positive women were estimated to report PID versus 2.3% (95% CI 1.3–3.4) of Pgp3MBA-negative women (PR 3.1; 95% CI 1.7–5.9). PID prevalence did not vary by age, nor self-reported recent sexually transmitted disease among US women, but was higher among non-Hispanic black women compared to non-Hispanic white women (PR 2.2; 95% CI 1.4–3.5). Conclusion Nearly one-third of US women have had CT by Pgp3MBA, with differences by race/ethnicity. Women with prior CT had three times the reported PID prevalence of women without CT. Further serologic research may refine the population-level impact of CT prevention activities, such as recommended annual CT screening, on PID incidence, particularly among non-Hispanic black women. Disclosures All Authors: No reported disclosures


2018 ◽  
Vol 201 (2) ◽  
Author(s):  
Nicholas A. Wood ◽  
Krystal Y. Chung ◽  
Amanda M. Blocker ◽  
Nathalia Rodrigues de Almeida ◽  
Martin Conda-Sheridan ◽  
...  

ABSTRACTMembers ofChlamydiaare obligate intracellular bacteria that differentiate between two distinct functional and morphological forms during their developmental cycle, elementary bodies (EBs) and reticulate bodies (RBs). EBs are nondividing small electron-dense forms that infect host cells. RBs are larger noninfectious replicative forms that develop within a membrane-bound vesicle, termed an inclusion. Given the unique properties of each developmental form of this bacterium, we hypothesized that the Clp protease system plays an integral role in proteomic turnover by degrading specific proteins from one developmental form or the other.Chlamydiaspp. have five uncharacterizedclpgenes,clpX,clpC, twoclpPparalogs, andclpB. In other bacteria, ClpC and ClpX are ATPases that unfold and feed proteins into the ClpP protease to be degraded, and ClpB is a deaggregase. Here, we focused on characterizing the ClpP paralogs. Transcriptional analyses and immunoblotting determined that these genes are expressed midcycle. Bioinformatic analyses of these proteins identified key residues important for activity. Overexpression of inactiveclpPmutants inChlamydiaspp. suggested independent function of each ClpP paralog. To further probe these differences, we determined interactions between the ClpP proteins using bacterial two-hybrid assays and native gel analysis of recombinant proteins. Homotypic interactions of the ClpP proteins, but not heterotypic interactions between the ClpP paralogs, were detected. Interestingly, protease activity of ClpP2, but not ClpP1, was detectedin vitro. This activity was stimulated by antibiotics known to activate ClpP, which also blocked chlamydial growth. Our data suggest the chlamydial ClpP paralogs likely serve distinct and critical roles in this important pathogen.IMPORTANCEChlamydia trachomatisis the leading cause of preventable infectious blindness and of bacterial sexually transmitted infections worldwide. Chlamydiae are developmentally regulated obligate intracellular pathogens that alternate between two functional and morphologic forms, with distinct repertoires of proteins. We hypothesize that protein degradation is a critical aspect to the developmental cycle. A key system involved in protein turnover in bacteria is the Clp protease system. Here, we characterized the two chlamydial ClpP paralogs by examining their expression inChlamydiaspp., their ability to oligomerize, and their proteolytic activity. This work will help understand the evolutionarily diverse Clp proteases in the context of intracellular organisms, which may aid in the study of other clinically relevant intracellular bacteria.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Rosa Sessa ◽  
Marisa Di Pietro ◽  
Fiorenzo De Santis ◽  
Simone Filardo ◽  
Rino Ragno ◽  
...  

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.


2005 ◽  
Vol 26 (2) ◽  
pp. 65 ◽  
Author(s):  
Peter Timms

Chlamydiae are obligate intracellular bacterial pathogens able to infect and cause serious disease in humans, birds and a remarkably wide range of warm and cold-blooded animals. The family Chlamydiaciae have traditionally been defined by their unique biphasic developmental cycle, involving the interconversion between an extracellular survival form, the elementary body and an intracellular replicative form, the reticulate body. However, as with many other bacteria, molecular approaches including 16SrRNA sequence are becoming the standard of choice. As a consequence, the chlamydiae are in a taxonomic state of flux. Prior to 1999, the family Chlamydiaceae consisted of one genus, Chlamydia, and four species, Chlamydia trachomatis, C. psittaci, C. pecorum and C. pneumoniae. In 1999, Everett et al proposed a reclassification of Chlamydia into two genera (Chlamydia and Chlamydophila) and nine species (Chlamydia trachomatis, C. suis, and C. muridarum and Chlamydophila psittaci, C. pneumoniae, C. felis, C. pecorum, C. abortus, and C. caviae). While some of these species are thought to be host specific (C. suis ? pigs, C. muridarum ? mice, C. felis ? cats, C. caviae ? guinea pigs) many are known to infect and cause disease in a wide range of hosts.


Sexual Health ◽  
2007 ◽  
Vol 4 (2) ◽  
pp. 133 ◽  
Author(s):  
Rodney W. Petersen ◽  
Sepehr N. Tabrizi ◽  
Suzanne Garland ◽  
Julie A. Quinlivan

Background: Chlamydia trachomatis is a major public health issue, with notifications of this sexually transmitted disease continuing to rise in Australia. Women attending colposcopy clinics are referred for treatment of cervical abnormalities often associated with human papilloma virus (HPV) infection. There is evidence that women who have acquired one sexually transmitted infection, such as HPV, are at higher risk of acquiring another. Women attending colposcopy clinics may therefore be at risk of undiagnosed infection with C. trachomatis. Aim: To determine the prevalence of C. trachomatis in women attending a public metropolitan colposcopy clinic in Victoria. Methods: A cross-sectional study was performed. Institutional ethics committee approval and informed consent were obtained. Consecutive women attending the colposcopy clinic completed a questionnaire and had a swab collected from the endocervix for analysis by polymerase chain reaction for C. trachomatis. Positive screens were treated in accordance with best practice. Data were analysed with Minitab Version 2004 (Minitab Inc, State College, PA, USA). Results: Of 581 women approached to participate in the trial, consent was obtained from 568 women (98%) and final outcome data was available on 560 women (99%). The overall rate of chlamydial infection was 2.1% (95% CI 1.5–2.7%). However, in women aged 25 years or less the rate was 5.8% (95% CI 3.8–7.8%) and in women over 25 years it was only 0.9% (95% CI 0.4–1.4%). Apart from age, no other demographic factor was significantly associated with chlamydial infection. Conclusion: Although the prevalence of chlamydial infection in the colposcopy clinic population as a whole does not warrant a policy for routine screening, screening directed at women aged 25 years or less would gain the greatest yields in terms of cost efficacy. Such a policy should be implemented as standard practice.


2019 ◽  
Vol 202 (1) ◽  
Author(s):  
Zhenyao Luo ◽  
Stephanie L. Neville ◽  
Rebecca Campbell ◽  
Jacqueline R. Morey ◽  
Shruti Menon ◽  
...  

Chlamydia trachomatis is the most common bacterial sexually transmitted infection in developed countries, with an estimated global prevalence of 4.2% in the 15- to 49-year age group. Although infection is asymptomatic in more than 80% of infected women, about 10% of cases result in serious disease. Infection by C. trachomatis is dependent on the ability to acquire essential nutrients, such as the transition metal iron, from host cells. In this study, we show that iron is the most abundant transition metal in C. trachomatis and report the structural and biochemical properties of the iron-recruiting protein YtgA. Knowledge of the high-resolution structure of YtgA will provide a platform for future structure-based antimicrobial design approaches.


2018 ◽  
Vol 200 (20) ◽  
Author(s):  
Malhar Desai ◽  
Wurihan Wurihan ◽  
Rong Di ◽  
Joseph D. Fondell ◽  
Bryce E. Nickels ◽  
...  

ABSTRACTThe obligate intracellular bacterial pathogenChlamydia trachomatishas a unique developmental cycle consisting of two contrasting cellular forms. Whereas the primaryChlamydiasigma factor, σ66, is involved in the expression of the majority of chlamydial genes throughout the developmental cycle, expression of several late genes requires the alternative sigma factor, σ28. In prior work, we identified GrgA as aChlamydia-specific transcription factor that activates σ66-dependent transcription by binding DNA and interacting with a nonconserved region (NCR) of σ66. Here, we extend these findings by showing GrgA can also activate σ28-dependent transcription through direct interaction with σ28. We measure the binding affinity of GrgA for both σ66and σ28, and we identify regions of GrgA important for σ28-dependent transcription. Similar to results obtained with σ66, we find that GrgA's interaction with σ28involves an NCR located upstream of conserved region 2 of σ28. Our findings suggest that GrgA is an important regulator of both σ66- and σ28-dependent transcription inC. trachomatisand further highlight NCRs of bacterial RNA polymerase as targets for regulatory factors unique to particular organisms.IMPORTANCEChlamydia trachomatisis the number one sexually transmitted bacterial pathogen worldwide. A substantial proportion ofC. trachomatis-infected women develop infertility, pelvic inflammatory syndrome, and other serious complications.C. trachomatisis also a leading infectious cause of blindness in underdeveloped countries. The pathogen has a unique developmental cycle that is transcriptionally regulated. The discovery of an expanded role for theChlamydia-specific transcription factor GrgA helps us understand the progression of the chlamydial developmental cycle.


1995 ◽  
Vol 3 (2) ◽  
pp. 82-88 ◽  
Author(s):  
Alex Allaire ◽  
Lawrence Nathan ◽  
Mark G. Martens

Chlamydia trachomatis is a sexually transmitted disease (STD) commonly diagnosed in pregnancy. C. trachomatis has been linked to several pregnancy complications including premature rupture of membranes (PROM), preterm labor and birth, low birth weight, intrauterine growth retardation, and postpartum endometritis. Infants born to mothers through an infected birth canal are at risk for acquiring C. trachomatis pneumonitis, conjunctivitis, and nasopharyngeal infection. The standard treatment of C. trachomatis in pregnancy is erythromycin. Recently, amoxicillin and clindamycin have been added as alternative regimens for those patients intolerant of erythromycin. This paper reviews the effectiveness and tolerance of the alternative regimens compared with erythromycin and the success of antepartum treatment of chlamydia in preventing the poor pregnancy outcome and neonatal morbidity associated with C. trachomatis.


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