Proportion of Pelvic Inflammatory Disease Cases Caused by<i>Chlamydia trachomatis</i>: Consistent Picture From Different Methods

Price, Malcolm J; Ades, A E; Welton, Nicky J; Simms, Ian; Macleod, John; Horner, Patrick J

doi:10.1093/infdis/jiw178

Cited by 48 publications

(48 citation statements)

References 31 publications

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“…Over 1.5 million cases of C. trachomatis genital infections were reported in the United States in 2015 alone ( 1 ). As many as 17% of females infected with C. trachomatis develop long-term infections in the genital tract, which can result in serious complications such as pelvic inflammatory disease (PID), fallopian-tube scarring, and ectopic pregnancy, all of which are major risk factors for tubal factor infertility (TFI) ( 2 ). Rectal infections with lymphogranuloma venereum (LGV) serovars of C. trachomatis can be invasive and, if untreated, can lead to complications such as proctocolitis, inguinal adenopathy, reactive arthropathy, and colorectal ulcers ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Genomewide Transcriptional Responses of Iron-Starved Chlamydia trachomatis Reveal Prioritization of Metabolic Precursor Synthesis over Protein Translation

2018

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By utilizing an experimental approach that monitors the immediate global response of Chlamydia trachomatis to iron starvation, clues to long-standing issues in Chlamydia biology are revealed, including how Chlamydia adapts to this stress. We determined that this pathogen initiates a transcriptional program that prioritizes replenishment of nutrient stores over replication, possibly in preparation for rapid growth once optimal iron levels are restored. Transcription of genes for biosynthesis of metabolic precursors was generally upregulated, while those involved in multiple steps of translation were downregulated. We also observed an increase in transcription of genes involved in DNA repair and neutralizing oxidative stress, indicating that Chlamydia employs an “all-or-nothing” strategy. Its small genome limits its ability to tailor a specific response to a particular stress. Therefore, the “all-or-nothing” strategy may be the most efficient way of surviving within the host, where the pathogen likely encounters multiple simultaneous immunological and nutritional insults.

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Section: Introductionmentioning

confidence: 99%

Genomewide Transcriptional Responses of Iron-Starved Chlamydia trachomatis Reveal Prioritization of Metabolic Precursor Synthesis over Protein Translation

2018

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“…The locus identifiers of genes in each identified cluster were submitted to KEGGMapper v2.8 to determine possible roles in specific biological pathways (52). For example, genes from the early-cycle DNA replication and repair cluster (Figure 7A) were mapped to multiple pathways including purine metabolism (5), pyrimidine metabolism (5), mismatch repair (5), replication (4), homologous recombination (3), double-stranded breaks repair (2), and base excision repair (1).…”

Section: Resultsmentioning

confidence: 99%

“…Over 1.5 million cases of C. trachomatis genital infections were reported in the US in 2015 alone (1). As many as 17% of females infected with C. trachomatis develop long-term infections in the genital tract, which can result in serious complications such as pelvic inflammatory disease (PID), fallopian-tube scarring, and ectopic pregnancy, all of which are major risk factors for tubal factor infertility (TFI) (2). Rectal infections with LGV serovars of C. trachomatis can be invasive, and if untreated can lead to complications such as proctocolitis, inguinal adenopathy, reactive arthropathy and colorectal ulcers (3).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide transcriptional responses of iron-starvedChlamydia trachomatisreveal prioritization of metabolic precursor synthesis over protein translation

Brinkworth

Wildung

Carabeo

2017

Preprint

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Iron is essential for growth and development of Chlamydia. Its long-term starvation in cultured mammalian cells leads to production of aberrant non-infectious chlamydial forms, also known as persistence. Immediate transcriptional responses to iron limitation have not been characterized, leaving a knowledge gap of how Chlamydia regulates its response to changes in iron availability. We used the fast-chelating agent 2,2’-Bipyridyl (BPDL) to homogeneously starve Chlamydia trachomatis serovar L2 of iron, starting at 6 or 12h post-infection. Immediate transcriptional responses were monitored after only 3 or 6h of BPDL-treatment, well before formation of aberrant Chlamydia. The first genome-wide transcriptional response of C. trachomatis to iron-starvation was subsequently determined utilizing RNA-sequencing. Only 7% and 8% of the genome was differentially expressed in response to iron-starvation at early and mid-stages of development, respectively. Biological pathway analysis revealed an overarching theme. Synthesis of macromolecular precursors (deoxynucleotides, amino acids, charged tRNAs, and acetyl-coA) was up-regulated, while energy-expensive processes (ABC transport and translation) were down-regulated. A large fraction of differentially down-regulated genes are involved in translation, including ribosome assembly, initiation and termination factors, which could be analogous to the translation down-regulation triggered by stress in other prokaryotes during stringent responses. Additionally, transcriptional up-regulation of DNA repair, oxidative stress, and tryptophan salvage genes reveals a possible coordination of responses to multiple antimicrobial and immunological insults. These responses of replicative-phase Chlamydia to iron-starvation indicate a prioritization of survival over replication, enabling the pathogen to “stock the pantry” with ingredients needed for rapid growth once optimal iron levels are restored.IMPORTANCEBy utilizing an experimental approach that monitors the immediate global response of Chlamydia trachomatis to iron-starvation, clues to long-standing questions in Chlamydia biology are revealed, including how Chlamydia adapts to this stress. We determined that this pathogen initiates a transcriptional program that prioritizes replenishment of nutrient stores over replication, possibly in preparation for rapid growth once optimal iron levels are restored. Transcription of genes for biosynthesis of metabolic precursors was generally up-regulated, while those involved in multiple steps of translation were down-regulated. We also observed an increase in transcription of genes involved in DNA repair and neutralizing oxidative stress, indicating that Chlamydia employs an “all-or-nothing” strategy. Its small genome limits its ability to tailor a specific response to a particular stress. Therefore, the “all-or-nothing” strategy may be the most efficient way of surviving within the host, where the pathogen likely encounters multiple simultaneous immunological and nutritional insults.

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“…Acute PID is a clinical syndrome with multiple etiologies [5]. The proportion caused by Ct varies by setting, but typically Ct is involved in about one third of cases [6]. Attribution of PID to a particular etiologic agent is difficult, as cervical and fallopian tube microbiologic tests do not always agree and co-infection is common.…”

Section: Goals Of a Vaccinementioning

confidence: 99%

National Institute of Allergy and Infectious Diseases workshop report: “Chlamydia vaccines: The way forward”

Zhong

Brunham

Maza

et al. 2019

Vaccine

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Chlamydia trachomatis (Ct), an intracellular pathogen, is the most common bacterial sexually transmitted infection. In addition to acute cervicitis and urethritis, Ct can lead to serious sequelae of significant public health burden including pelvic inflammatory disease (PID) and infertility. Ct control efforts have not resulted in desired outcomes such as reduced incidence and reinfection, and this highlights the need for the development of an effective Ct vaccine. To this end, NIAID organized a workshop to consider the current status of Ct vaccine research and address critical questions in Ct vaccine design and clinical testing. Topics included the goal(s) of a vaccine and the feasibility of achieving these goals, animal models of infection including mouse and nonhuman primate (NHP) models, and correlates of protection to guide vaccine design. Decades of research have provided both whole cell-based and subunit vaccine candidates for development. At least one is currently in clinical development and efforts now need to be directed toward further development of the most attractive candidates. Overall, the discussions and presentations from the workshop highlighted optimism about the current status of Ct vaccine research and detailed the remaining gaps and questions needed to move vaccines forward.

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Proportion of Pelvic Inflammatory Disease Cases Caused byChlamydia trachomatis: Consistent Picture From Different Methods

Cited by 48 publications

References 31 publications

Genomewide Transcriptional Responses of Iron-Starved Chlamydia trachomatis Reveal Prioritization of Metabolic Precursor Synthesis over Protein Translation

Genomewide Transcriptional Responses of Iron-Starved Chlamydia trachomatis Reveal Prioritization of Metabolic Precursor Synthesis over Protein Translation

Genome-wide transcriptional responses of iron-starvedChlamydia trachomatisreveal prioritization of metabolic precursor synthesis over protein translation

National Institute of Allergy and Infectious Diseases workshop report: “Chlamydia vaccines: The way forward”

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