scholarly journals Chlamydial infection and disease in the koala

2005 ◽  
Vol 26 (2) ◽  
pp. 65 ◽  
Author(s):  
Peter Timms
Keyword(s):  
Chlamydia Trachomatis ◽  
Chlamydial Infection ◽  
Developmental Cycle ◽  
Elementary Body ◽  
Obligate Intracellular ◽  
Molecular Approaches ◽  
Reticulate Body ◽  
Wide Range ◽  
The Family ◽  
Serious Disease

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.

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 Cell Type Development in Chlamydia trachomatis Follows a Program Intrinsic to the Reticulate Body

2020 ◽  
Author(s):  
Travis J Chiarelli ◽  
Nicole A Grieshaber ◽  
Anders Omsland ◽  
Christopher H Remien ◽  
Scott S Grieshaber
Keyword(s):  
Cell Division ◽  
Chlamydia Trachomatis ◽  
Mathematical Models ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Developmental Cycle ◽  
Cell Type ◽  
Obligate Intracellular ◽  
Reticulate Body ◽  
A Cell

AbstractThe obligate intracellular bacterial pathogen Chlamydia trachomatis (Ctr) is reliant on an unusual developmental cycle consisting of two cell forms termed the elementary body (EB) and the reticulate body (RB). The EB is infectious and utilizes a type III secretion system and preformed effector proteins during invasion, but does not replicate. The RB replicates in the host cell but is non-infectious. This developmental cycle is central to chlamydial pathogenesis. In this study we developed mathematical models of the chlamydial developmental cycle that account for potential factors influencing the timing of RB to EB cell type switching during infection. Our models predicted that two broad categories of regulatory signals for RB to EB development could be differentiated experimentally; an “intrinsic” cell autonomous program inherent to each RB or an “extrinsic” environmental signal to which RBs respond. To experimentally differentiate between these hypotheses, we tracked the expression of Ctr developmental specific promoters using fluorescent reporters and live cell imaging. These experiments indicated that EB production was not influenced by increased MOI or by superinfection, suggesting the cycle follows an intrinsic program that is not influenced by environmental factors. Additionally, live cell imaging of these promoter constructs revealed that EB development is a multistep process linked to RB growth rate and cell division. The formation of EBs followed a cell type gene expression progression with the promoters for euo and ihtA active in RBs, while the promoter for hctA was active in early EBs/intermediate cells and finally the promoters for the true late genes, hctB, scc2, and tarp active in the maturing EB.ImportanceChlamydia trachomatis is an obligate intracellular bacteria that can cause trachoma, cervicitis, urethritis, salpingitis, and pelvic inflammatory disease. To establish infection in host cells Chlamydia must complete a multi cell type developmental cycle. The developmental cycle consists of two specialized cells; the EB which mediates infection of new cells and the RB which replicates and eventually produces more EB cells to mediate the next round of infection. By developing and testing mathematical models to discriminate between two competing hypotheses for the nature of the signal controlling RB to EB cell type switching. We demonstrate that RB to EB development follows a cell autonomous program that does not respond to environmental cues. Additionally, we show that RB to EB development is a function of cell growth and cell division. This study serves to further our understanding of the chlamydial developmental cycle that is central to the bacterium’s pathogenesis.

scholarly journals Role for GrgA in Regulation of σ28-Dependent Transcription in the Obligate Intracellular Bacterial PathogenChlamydia trachomatis

2018 ◽  
Vol 200 (20) ◽  
Author(s):  
Malhar Desai ◽  
Wurihan Wurihan ◽  
Rong Di ◽  
Joseph D. Fondell ◽  
Bryce E. Nickels ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Chlamydia Trachomatis ◽  
Sigma Factor ◽  
Bacterial Pathogen ◽  
Direct Interaction ◽  
Developmental Cycle ◽  
Content Type ◽  
Sexually Transmitted ◽  
Obligate Intracellular ◽  
Specific Transcription Factor

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.

scholarly journals Growth Cycle-Dependent Pharmacodynamics of Antichlamydial Drugs

2005 ◽  
Vol 49 (5) ◽  
pp. 1852-1856 ◽  
Author(s):  
Katrin Siewert ◽  
Jan Rupp ◽  
Matthias Klinger ◽  
Werner Solbach ◽  
Jens Gieffers
Keyword(s):  
Chlamydial Infection ◽  
Late Phase ◽  
Growth Cycle ◽  
Developmental Cycle ◽  
Obligate Intracellular ◽  
Chlamydial Species ◽  
Cycle Dependent ◽  
Dose Dependent

ABSTRACT Chlamydiae are obligate intracellular pathogens that exhibit an extensive intracellular developmental cycle in vivo. Clinical treatment of chlamydial infection is typically initiated upon occurrence of symptomatology and is directed against an asynchronous population of different chlamydial developmental forms. Pharmacodynamics of antichlamydial drugs are predominantly characterized by MICs; however, in vitro determinations of MIC may not reflect differential susceptibilities of the developmental cycle. In this study, we correlated the antichlamydial effect of erythromycin, rifampin, doxycycline, and ciprofloxacin with the developmental stage of a fast-replicating and a slow-replicating chlamydial species. In addition, we describe the influence of concentration on killing. Extracellular elementary bodies and very-early-phase and late-phase chlamydiae were refractory to all tested antibiotics except rifampin, which was very effective against early-cycle chlamydiae. Rifampin was the most effective antibiotic overall, killed in a dose dependent matter, and exhibited moderate synergism with erythromycin. These considerations provide important information on chlamydial biology and antimicrobial susceptibility. A combinational therapy of rifampin and a macrolide should be considered in therapy-refractory infections.

scholarly journals Translational gene expression control in Chlamydia trachomatis.

2021 ◽  
Author(s):  
Nicole A Grieshaber ◽  
Travis J Chiarelli ◽  
Cody R Appa ◽  
Grace Neiswanger ◽  
Kristina Peretti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chlamydia Trachomatis ◽  
Translational Control ◽  
Regulatory Protein ◽  
Inducible Promoter ◽  
Cloning And Expression ◽  
Developmental Cycle ◽  
Expression Control ◽  
Gene Expression Control ◽  
Wide Range

The human pathogen Chlamydia trachomatis proceeds through a multi phenotypic developmental cycle with each cell form specialized for different roles in pathogenesis. Understanding the mechanisms regulating this complex cycle has historically been hampered by limited genetic tools. In an effort to address this issue, we developed a translational control system to regulate gene expression in Chlamydia using a synthetic riboswitch. Here we demonstrate that translational control via a riboswitch can be used in combination with a wide range of promoters in C. trachomatis. The synthetic riboswitch E, inducible with theophylline, was used to replace the ribosome binding site of the synthetic promoter T5-lac, the native chlamydial promoter of the pgp4plasmid gene and an anhydrotetracycline responsive promoter. In all cases the riboswitch inhibited translation, and high levels of protein expression was induced with theophylline. Combining the Tet transcriptional inducible promoter with the translational control of the riboswitch resulted in strong repression and allowed for the cloning and expression of the potent chlamydial regulatory protein, HctB. The ability to control the timing and strength of gene expression independently from promoter specificity is a new and important tool for studying chlamydial regulatory and virulence genes.

scholarly journals Stochastic modelling of chlamydial infections

2020 ◽  
Vol 61 ◽  
pp. C89-C103
Author(s):  
Torrington Callan ◽  
Stephen Woodcock
Keyword(s):  
Mathematical Model ◽  
Immune Response ◽  
Chlamydia Trachomatis ◽  
Chlamydial Infection ◽  
Branching Processes ◽  
Stochastic Modelling ◽  
Cell Aggregation ◽  
Computational Techniques ◽  
Developmental Cycle ◽  
Ascending Infection

Chlamydia trachomatis is a bacterial pathogen that can cause serious reproductive harm. We describe a class of stochastic branching processes and their application in modelling the growth of an infection by Chlamydia. Using simulations we show that the model can reproduce biological phenomena of interest, and we show the variability in outcomes of infections under the same parameter conditions. We further speculate how this model might be used to explain long-term adverse reproductive sequelae. References Y. M. AbdelRahman and R. J. Belland. The chlamydial developmental cycle. FEMS Microbio. Rev., 29(5):949–959, 2005. doi:10.1016/j.femsre.2005.03.002. T. E. Harris. Branching processes. Ann. Math. Stat., 19(4):474–494, 12 1948. doi:10.1214/aoms/1177730146. C. Jacob. Branching processes: Their role in epidemiology. Int. J. Env. Res. Public Health, 7(3):1186–1204, 2019. doi:10.3390/ijerph7031204. N. Low, M. Egger, J. A. C. Sterne, R. M. Harbord, F. Ibrahim, B. Lindblom, and B. Herrmann. Incidence of severe reproductive tract complications associated with diagnosed genital chlamydial infection: The Uppsala women's cohort study. Sexually Trans. Infect., 82(3):212–218, 2006. doi:10.1136/sti.2005.017186. D. Mallet, M. Bagher-Oskouei, A. Farr, D. Simpson, and K. Sutton. A mathematical model of chlamydial infection incorporating movement of chlamydial particles. Bull. Math. Bio., 75:2257–2270, 10 2013. doi:10.1007/s11538-013-9891-9. H. K. Maxion, W. Liu, M.-H. Chang, and K. A. Kelly. The infecting dose of chlamydia muridarum modulates the innate immune response and ascending infection. Infect. Immun., 72(11):6330–6340, 2004. doi:10.1128/IAI.72.11.6330-6340.2004. S. Menon, P. Timms, J. A. Allan, K. Alexander, L. Rombauts, P. Horner, M. Keltz, J. Hocking, and W. M. Huston. Human and pathogen factors associated with chlamydia trachomatis-related infertility in women. Clinic. Microbio. Rev., 28(4):969–985, 2015. doi:10.1128/CMR.00035-15. D. P. Wilson. Mathematical modelling of chlamydia. In J. Crawford and A. J. Roberts, editors, Proc. of 11th Computational Techniques and Applications Conference CTAC-2003, ANZIAM J., volume 45, pages C201–C214, 2004. doi:10.21914/anziamj.v45i0.883. D. P. Wilson and D. L. S. McElwain. A model of neutralization of chlamydia trachomatis based on antibody and host cell aggregation on the elementary body surface. J. Theor. Bio., 226(3):321–330, 2004. doi:10.1016/j.jtbi.2003.09.010. D. P. Wilson, P. Timms, and D. L. S. McElwain. A mathematical model for the investigation of the Th1 immune response to chlamydia trachomatis. Math. Biosci., 182(1):27–44, 2003. doi:10.1016/S0025-5564(02)00180-3.

Chlamydiosis

2011 ◽  
Author(s):  
Margaret Sillis ◽  
David Longbottom
Keyword(s):  
Control Strategies ◽  
Risk Groups ◽  
Developmental Cycle ◽  
Zoonotic Infections ◽  
The United Kingdom ◽  
Reticulate Body ◽  
Wide Range ◽  
Poultry Processing ◽  
Variable Success ◽  
Obligate Intracellular Bacteria

Chlamydial pathogens cause a wide-range of infections and disease, known as chlamydioses, in humans, other mammals and birds. The causative organisms are Gram-negative obligate intracellular bacteria that undergo a unique biphasic developmental cycle involving the infectious elementary body and the metabolically-active, non-infectious reticulate body. At least two species, Chlamydophila psittaci and Chlamydophila abortus, are recognized as causes of zoonotic infections in humans worldwide, mainly affecting persons exposed to infected psittacine and other birds, especially ducks, turkeys, and pigeons, and less commonly to animals, particularly sheep. Outbreaks occur amongst aviary workers, poultry processing workers, and veterinarians. Infection is transmitted through inhalation of infected aerosols contaminated by avian droppings, nasal discharges, or products of ovine gestation or abortion. Person to person transmission is rare. Control strategies have met with variable success depending on the degree of compliance or enforcement of legislation. In the United Kingdom control is secondary, resulting from protection of national poultry flocks by preventing the importation of Newcastle disease virus using quarantine measures. Improved standards of husbandry, transport conditions, and chemoprophylaxis are useful for controlling reactivation of latent avian chlamydial infection. Vaccination has had limited effect in controlling ovine infection. Improved education of persons in occupational risk groups and the requirement for notification may encourage a more energetic approach to its control.

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
Keyword(s):  
Chlamydia Trachomatis ◽  
Transmitted Disease ◽  
Primary Source ◽  
Host Cells ◽  
Elementary Body ◽  
Sexually Transmitted ◽  
Obligate Intracellular ◽  
Survival And Growth ◽  
Immunoperoxidase Labeling ◽  
Preventable Blindness

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.

scholarly journals Kinematics of Intracellular Chlamydiae Provide Evidence for Contact-Dependent Development

2009 ◽  
Vol 191 (18) ◽  
pp. 5734-5742 ◽  
Author(s):  
David P. Wilson ◽  
Judith A. Whittum-Hudson ◽  
Peter Timms ◽  
Patrik M. Bavoil
Keyword(s):  
Chlamydia Trachomatis ◽  
Developmental Stages ◽  
Elementary Body ◽  
Average Speed ◽  
Dependent Development ◽  
Reticulate Body ◽  
Size Type ◽  
The Relationship ◽  
Chlamydial Inclusion ◽  
Present Experimental Evidence

ABSTRACT A crucial process of chlamydial development involves differentiation of the replicative reticulate body (RB) into the infectious elementary body (EB). We present experimental evidence to provide support for a contact-dependent hypothesis for explaining the trigger involved in differentiation. We recorded live-imaging of Chlamydia trachomatis-infected McCoy cells at key times during development and tracked the temporospatial trajectories of individual chlamydial particles. We found that movement of the particles is related to development. Early to mid-developmental stages involved slight wobbling of RBs. The average speed of particles increased sharply at 24 h postinfection (after the estimated onset of RB to EB differentiation). We also investigated a penicillin-supplemented culture containing EBs, RBs, and aberrantly enlarged, stressed chlamydiae. Near-immobile enlarged particles are consistent with their continued tethering to the chlamydial inclusion membrane (CIM). We found a significantly negative, nonlinear association between speed and size/type of particles, providing further support for the hypothesis that particles become untethered near the onset of RB to EB differentiation. This study establishes the relationship between the motion properties of the chlamydiae and developmental stages, whereby wobbling RBs gradually lose contact with the CIM, and RB detachment from the CIM is coincidental with the onset of late differentiation.

scholarly journals Persistence alters the interaction between Chlamydia trachomatis and its host cell.

2021 ◽  
Author(s):  
Mary R. Brockett ◽  
George W. Liechti
Keyword(s):  
Chlamydia Trachomatis ◽  
Effector Proteins ◽  
Developmental Cycle ◽  
Intracellular Pathogen ◽  
Obligate Intracellular ◽  
Peptide Labeling ◽  
Extracellular Form ◽  
Response To Stress ◽  
Obligate Intracellular Pathogen ◽  
Late Stages

In response to stress, the obligate intracellular pathogen Chlamydia trachomatis stops dividing and halts its biphasic developmental cycle. The infectious, extracellular form of this bacterium is highly susceptible to killing by the host immune response, and by pausing development Chlamydia can survive in an intracellular, ‘aberrant’ state for extended periods of time. The relevance of these aberrant forms has long been debated, and many questions remain concerning how they contribute to the persistence and pathogenesis of the organism. Using reporter cell lines, fluorescence microscopy, and a di-peptide labeling strategy, we measured the ability of C. trachomatis to synthesize, assemble, and degrade peptidoglycan under various aberrance-inducing conditions. We found that all aberrance-inducing conditions affect chlamydial peptidoglycan, and that some actually halt the biosynthesis pathway early enough to prevent the release of an immunostimulatory peptidoglycan component, muramyl tripeptide. In addition, utilizing immunofluorescence and electron microscopy, we determined that the induction of aberrance can detrimentally affect the development of the microbe’s pathogenic vacuole (the inclusion). Taken together, our data indicate that aberrant forms of Chlamydia generated by different environmental stressors can be sorted into two broad categories based on their ability to continue releasing peptidoglycan-derived, immunostimulatory muropeptides and their ability to secrete effector proteins that are normally expressed at the mid- and late- stages of the microbe’s developmental cycle. Our findings reveal a novel, immuno-evasive feature inherent to a subset of aberrant chlamydial forms and provide clarity and context to the numerous persistence mechanisms employed by these ancient, genetically-reduced microbes.

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