scholarly journals Diagnosis of Chlamydia trachomatis using self-collected non-invasive specimens ? the Australian experience

2007 ◽  
Vol 28 (1) ◽  
pp. 12
Author(s):  
Sepehr N. Tabrizi

Chlamydia trachomatis are small, non-motile, obligate intracellular bacteria that typically infect human eukaryotic columnar epithelial cells. C. trachomatis infections result in a number of diseases of worldwide public health concern, including trachoma, lymphogranuloma venereum (LGV) and urogenital infections. Chlamydia is the most common sexually transmitted bacterial pathogen worldwide and in Australia has exhibited a steady rise in prevalence 1. National notification rates of newly diagnosed chlamydia infections have increased nearly four-fold since 1994 and more than doubled since 1999.

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.


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.


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

ABSTRACTThe sexually transmitted obligate intracellular bacterial pathogen Chlamydia trachomatis has a unique developmental cycle consisting of two contrasting cellular forms. Whereas the primary Chlamydia sigma 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 a Chlamydia-specific transcription factor that activates σ66-dependent transcription by binding DNA and interacting with a non-conserved 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 σ28 involves a NCR located upstream of conserved region 2 of σ28. Our findings suggest GrgA is an important regulator of both σ66- and σ28-dependent transcription in C. trachomatis and further highlight NCRs of bacterial RNA polymerase as targets for regulatory factors unique to particular organisms.


2008 ◽  
Vol 8 (1) ◽  
pp. 42 ◽  
Author(s):  
Yvonne Pannekoek ◽  
Giovanna Morelli ◽  
Barica Kusecek ◽  
Servaas A Morré ◽  
Jacobus M Ossewaarde ◽  
...  

2005 ◽  
Vol 73 (3) ◽  
pp. 1399-1403 ◽  
Author(s):  
Songmin Ying ◽  
Barbara M. Seiffert ◽  
Georg Häcker ◽  
Silke F. Fischer

ABSTRACT Chlamydiae are obligate intracellular bacteria that can inhibit apoptosis of their host cell. As shown recently, this inhibition is in part explained by the proteolytic degradation of the proapoptotic Bcl-2 family members (BH3-only proteins) Bim, Puma, and Bad upon chlamydial infection. In this study, we further explore this antiapoptotic mechanism. In cells infected with a Chlamydia trachomatis L2 strain, Bim, Puma, and Bad were degraded with similar kinetics, and the degradation of all three was blocked by inhibition of the proteasome. Furthermore, the BH3-only proteins Bmf, Noxa, and tBid were also targeted by chlamydial infection. The constitutively expressed Bmf disappeared during infection. When Noxa was experimentally induced, the levels were also reduced by infection with C. trachomatis. In death-receptor-induced apoptosis, cleaved and activated tBid was degraded, and this destruction was also prevented by inhibition of the proteasome. These results show that chlamydial infection leads to a broad degradation of BH3-only proteins. This loss of proapoptotic factors can explain the almost general protection of infected cells against apoptotic stimuli.


2009 ◽  
Vol 53 (4) ◽  
pp. 1482-1489 ◽  
Author(s):  
M. C. Skinner ◽  
W. E. Stamm ◽  
M. L. Lampe

ABSTRACT A topical microbicide that women can use to prevent sexually transmitted diseases (STDs) is essential, and many microbicide candidates are being tested for activity against human immunodeficiency virus and other STDs, including Chlamydia trachomatis. Screening assays for assessing the activity of microbicides against C. trachomatis are typically done with laboratory-adapted strains, but it is possible that recent clinical isolates may have different susceptibilities to microbicides, as has been seen with Neisseria gonorrhoeae and Lactobacillus spp. (B. J. Moncla and S. L. Hillier, Sex. Transm. Dis. 32:491-494, 2005). We utilized three types of microbicides to help define this aspect of our assay to test microbicides against C. trachomatis in vitro. To simulate conditions of transmission, we used an assay that we previously developed in which we exposed chlamydial elementary bodies to microbicides prior to contact with epithelial cells. We first determined the toxicity of microbicides to the cells used to culture Chlamydia trachomatis in the assay and, if necessary, modified the assay to eliminate toxicity at the concentrations tested. We compared the sensitivities of recent clinical isolates of Chlamydia trachomatis versus laboratory strains of the same serovar and found major differences in sensitivity to nonoxynol-9 (non-9), but only minor differences were seen with the other microbicides. We thus conclude that when assessing activity of potential topical microbicides versus the obligate intracellular bacteria C. trachomatis, the use of recent clinical isolates may not be necessary to draw a conclusion about a microbicide's effectiveness. However, it is important to keep in mind that differences (like those seen with non-9) are possible and that clinical isolates could be included in later stages of testing.


2015 ◽  
Vol 84 (3) ◽  
pp. 612-621 ◽  
Author(s):  
Anna J. Hooppaw ◽  
Derek J. Fisher

Chlamydiaspp. are ubiquitous, obligate, intracellular Gram-negative bacterial pathogens that undergo a unique biphasic developmental cycle transitioning between the infectious, extracellular elementary body and the replicative, intracellular reticulate body. The primaryChlamydiaspecies associated with human disease areC. trachomatis, which is the leading cause of both reportable bacterial sexually transmitted infections and preventable blindness, andC. pneumoniae, which infects the respiratory tract and is associated with cardiovascular disease. Collectively, these pathogens are a significant source of morbidity and pose a substantial financial burden on the global economy. Past efforts to elucidate virulence mechanisms of these unique and important pathogens were largely hindered by an absence of genetic methods. Watershed studies in 2011 and 2012 demonstrated that forward and reverse genetic approaches were feasible withChlamydiaand that shuttle vectors could be selected and maintained within the bacterium. While these breakthroughs have led to a steady expansion of the chlamydial genetic tool kit, there are still roads left to be traveled. This minireview provides a synopsis of the currently available genetic methods forChlamydiaalong with a comparison to the methods used in other obligate intracellular bacteria. Limitations and advantages of these techniques will be discussed with an eye toward the methods still needed, and how the current state of the art for genetics in obligate intracellular bacteria could direct future technological advances forChlamydia.


2021 ◽  
Author(s):  
Arkaprabha Banerjee ◽  
David E Nelson

Abstract Multiple species of obligate intracellular bacteria in the genus Chlamydia are important veterinary and/or human pathogens. These pathogens all share similar biphasic developmental cycles and transition between intracellular vegetative reticulate bodies and infectious elementary forms, but vary substantially in their host preferences and pathogenic potential. A lack of tools for genetic engineering of these organisms has long been an impediment to the study of their biology and pathogenesis. However, the refinement of approaches developed in C. trachomatis over the last ten years, and adaptation of some of these approaches to other Chlamydia spp. in just the last few years, has opened exciting new possibilities for studying this ubiquitous group of important pathogens.


2013 ◽  
Author(s):  
Walter E Stamm

The Chlamydiaceae are obligate intracellular bacteria that produce a wide variety of infections in many mammalian and avian species. Three species belonging to two genera of Chlamydiaceae infect humans: Chlamydia trachomatis, Chlamydophila psittaci, and Chlamydophila pneumoniae. C. trachomatis is exclusively a human pathogen and is transmitted from person to person via sexual contact, perinatal transmission, or close contact in households. C. psittaci, in contrast, is more widely distributed in nature, producing genital, conjunctival, intestinal, or respiratory infections in many avian and mammalian species. C. pneumoniae is a fastidious organism that produces upper respiratory tract infection and pneumonitis in both children and adults. This chapter details the epidemiology, pathogenesis, diagnosis, and treatment of chlamydial diseases. Sexually transmitted diseases, perinatal infections, adult inclusion conjunctivitis, trachoma, and psittacosis are covered. The chapter also includes tables outlining comparative features of the three species and treatment of sexually transmitted diseases caused by C. trachomatis, as well as a figure illustrating the life cycle of Chlamydiaceae.  This review contains 1 highly rendered figure, 2 tables, and 87 references.


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