Chlamydia trachomatis responds to heat shock, penicillin induced persistence, and IFN-gamma persistence by altering levels of the extracytoplasmic stress response protease HtrA

Huston, Wilhelmina M.; Theodoropoulos, Christina; Mathews, Sarah A.; Timms, Peter

doi:10.1186/1471-2180-8-190

Cited by 59 publications

(72 citation statements)

References 39 publications

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“…nlm.nih.gov) (43). CT823/TC0210 (HtrA) is a temperatureactivated serine endoprotease showing both chaperon and protease activities and probably is involved in chlamydial defense during conditions of high protein stress (44). Finally, CT153/TC0431 belongs to the MAC/perforin family, a class of proteins performing critical functions in innate and adaptive immunity.…”

Section: Discussionmentioning

confidence: 99%

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Finco

Frigimelica

Buricchi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Natural immunity against obligate and/or facultative intracellular pathogens is usually mediated by both humoral and cellular immunity. The identification of those antigens stimulating both arms of the immune system is instrumental for vaccine discovery. Although high-throughput technologies have been applied for the discovery of antibody-inducing antigens, few examples of their application for T-cell antigens have been reported. We describe how the compilation of the immunome, here defined as the pool of immunogenic antigens inducing T- and B-cell responses in vivo, can lead to vaccine candidates against Chlamydia trachomatis . We selected 120 C. trachomatis proteins and assessed their immunogenicity using two parallel high-throughput approaches. Protein arrays were generated and screened with sera from C. trachomatis -infected patients to identify antibody-inducing antigens. Splenocytes from C. trachomatis -infected mice were stimulated with 79 proteins, and the frequency of antigen-specific CD4 + /IFN-γ + T cells was analyzed by flow cytometry. We identified 21 antibody-inducing antigens, 16 CD4 + /IFN-γ + –inducing antigens, and five antigens eliciting both types of responses. Assessment of their protective activity in a mouse model of Chlamydia muridarum lung infection led to the identification of seven antigens conferring partial protection when administered with LTK63/CpG adjuvant. Protection was largely the result of cellular immunity as assessed by CD4 + T-cell depletion. The seven antigens provided robust additive protection when combined in four-antigen combinations. This study paves the way for the development of an effective anti- Chlamydia vaccine and provides a general approach for the discovery of vaccines against other intracellular pathogens.

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Section: Discussionmentioning

confidence: 99%

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Finco

Frigimelica

Buricchi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…The semi-purified EB was resuspended in SPG and stored at −80°C. [11][12][13] Serial dilutions of the suspension obtained were used for EB quantification. HEp-2 cells were fixed and stained with monoclonal antibody-fluorescein isothiocyanate.…”

Section: Chlamydia Trachomatis Cell Culture and Preparation Of Semi-pmentioning

confidence: 99%

Systemic Antibody Response to Chlamydia Trachomatis Infection in Patients Either Infected or Reinfected with Different Chlamydia Serovars

Gupta

Waugh

Ziklo

et al. 2017

Indian Journal of Medical Microbiology

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Original Article IntroductIonChlamydia trachomatis is the leading cause of bacterial sexually transmitted infection (STI) in humans.[1] The prevalence of C. trachomatis infection has been rising progressively in many countries, with >100 million new cases estimated annually around the globe (WHO).[2] An estimated 3-4 million new cases occur every year in the US, 5 million in Western Europe and 16 million in Sub-Saharan Africa.[3] The largest burden of C. trachomatis infection occurs in women, where complications can include pelvic inflammatory disease. However, because patients with C. trachomatis urogenital infections often do not exhibit any symptoms (75%-90% of patients), they remain undiagnosed and untreated. This can lead to tubal factor infertility, miscarriage or ectopic pregnancy. [4][5][6] Genital Chlamydia infections also increase the susceptibility to other sexually transmitted agents, such as HIV. [7] Repeated chlamydial genital infections are common and account for a substantial proportion of incident infections.[8]Although C. trachomatis infections can be treated effectively with antibiotics such as azithromycin, or doxycycline, almost one-fourth of individuals are re-infected with C. trachomatis.[9]Repeated infections result from failure of antibiotic therapy or from reinfection due to continued unprotected sexual contact Introduction: Chlamydia trachomatis is the etiological agent for the most prevalent bacterial sexually transmitted infection in both developed and developing countries. The aim of present study was to characterize the antibody response between two groups of individuals, having either a single C. trachomatis infection and or repeated infections. Material and Methods: Current study consisted of two groups, one with an initial Chlamydia infection and a second with repeated infections. A titre based estimation of specific serum (IgG and IgA) levels using ELISA were performed, which further validated by western blot. In vitro neutralizing ability of each patient's serum against both homologous and heterologous strains was also determined. Results: Individuals infected with one of the C. trachomatis serovars D, E or K exhibited a strong systemic antibody response as characterized by ELISA and western blot. These individuals may have developed at least some level of protection as they only represented single infection. By comparison, individuals infected with serovar D, E or F that exhibited low systemic antibody response often presented repeated C. trachomatis infections, suggesting an association with poor immune response. An in vitro neutralizing level of 60-90% was observed in the human sera against homologous serovar D and two heterologous C. trachomatis serovars E and K, compared to <40% against heterologous serovars F. Conclusion: Individuals infected with serovars D and K showed a potential association between circulating antibody response and re-infection risk. While the patients infected with serovars E showed a disconnection between systemic antibody response and re-...

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“…Therefore, it is unknown whether any experimental chlamydial vaccine candidates could have a therapeutic effect, whether they might reduce or enhance pathological sequelae, or whether they could cause chronic, persistent infections, when administered during an infection. Knowing that Chlamydia can enter a persistent state when put under various pressures, including cytokine production, [92][93][94][95][96][97][98][99][100][101][102][103][104][105] it is plausible that enhancement of infection-induced immune responses by vaccination may cause the Chlamydia to enter this state and promote both pathology development and future reactivation of infection. It is also unknown whether any vaccine candidates administered after resolution of a previous genital infection will further boost the individual's infection-induced immune response, provide a greater level of protection and prevent further pathology development.…”

Section: Problems With Vaccine Developmentmentioning

confidence: 99%

REVIEW ARTICLE: Chlamydia trachomatis, a Hidden Epidemic: Effects on Female Reproduction and Options for Treatment

Carey

Beagley

2010

American J Rep Immunol

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Citation Carey AJ, Beagley KW. Chlamydia trachomatis, a hidden epidemic: effects on the female reproduction and options for treatment. Am J Reprod Immunol 2010The number of genital tract Chlamydia trachomatis infections is steadily increasing worldwide, with approximately 50–70% of infections asymptomatic. There is currently no uniform screening practice, current antibiotic treatment has failed to prevent the increased incidence, and there is no vaccine available. We examined studies on the epidemiology of C. trachomatis infections, the effects infections have on the female reproductive tract and subsequent reproductive health and what measures are being taken to reduce these problems. Undetected or multiple infections in women can lead to the development of severe reproductive sequelae, including pelvic inflammatory disease and tubal infertility. There are two possible paradigms of chlamydial pathogenesis, the cellular and immunological paradigms. While many vaccine candidates are being extensively tested in animal models, they are still years from clinical trials. With no vaccine available and antibiotic treatment unable to halt the increased incidence, infection rates will continue to increase and cause a significant burden on health care systems.

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Chlamydia trachomatis responds to heat shock, penicillin induced persistence, and IFN-gamma persistence by altering levels of the extracytoplasmic stress response protease HtrA

Cited by 59 publications

References 39 publications

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Systemic Antibody Response to Chlamydia Trachomatis Infection in Patients Either Infected or Reinfected with Different Chlamydia Serovars

REVIEW ARTICLE: Chlamydia trachomatis, a Hidden Epidemic: Effects on Female Reproduction and Options for Treatment

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