Advances in genetic manipulation of Chlamydia trachomatis

Wan, Weiqiang; Li, Danni; Li, Dan; Jiao, Jun

doi:10.3389/fimmu.2023.1209879

Cited by 4 publications

(3 citation statements)

References 81 publications

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“…Recently, genetic methods have rapidly progressed and accordingly our understanding of pathogenic mechanisms has increased ( Fisher and Beare, 2023 ). However, each genetic approach has their advantages and limitations [reviewed in, ( Banerjee and Nelson, 2021 ; Wan et al., 2023 )]. Previously, Chlamydia was thought to be genetically intractable due to its intracellular development, vacuole niche, evasive persistence mechanism, serovar genetic variability, and the thick wall of EB absorbing external DNA ( Andersen et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Molecular pathogenesis of Chlamydia trachomatis

Jury,

Fleming,

Huston

et al. 2023

Front. Cell. Infect. Microbiol.

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Chlamydia trachomatis is a strict intracellular human pathogen. It is the main bacterial cause of sexually transmitted infections and the etiologic agent of trachoma, which is the leading cause of preventable blindness. Despite over 100 years since C. trachomatis was first identified, there is still no vaccine. However in recent years, the advancement of genetic manipulation approaches for C. trachomatis has increased our understanding of the molecular pathogenesis of C. trachomatis and progress towards a vaccine. In this mini-review, we aimed to outline the factors related to the developmental cycle phase and specific pathogenesis activity of C. trachomatis in order to focus priorities for future genetic approaches. We highlight the factors known to be critical for developmental cycle stages, gene expression regulatory factors, type III secretion system and their effectors, and individual virulence factors with known impacts.

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Section: Introductionmentioning

confidence: 99%

Molecular pathogenesis of Chlamydia trachomatis

Jury,

Fleming,

Huston

et al. 2023

Front. Cell. Infect. Microbiol.

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“…Despite recent advancements in the genetic manipulation of Chlamydia ( 20 , 21 ), the tools available to study essential genes in this obligate intracellular bacterium remain limited. We attempted but failed to disrupt grgA through group II intron (Targetron) insertional mutagenesis ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

Requirement of GrgA for Chlamydia infectious progeny production, optimal growth, and efficient plasmid maintenance

Lu,

Wang,

Wurihan

et al. 2024

mBio

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Chlamydia , an obligate intracellular bacterial pathogen, has a unique developmental cycle involving the differentiation of invading elementary bodies (EBs) to noninfectious reticulate bodies (RBs), replication of RBs, and redifferentiation of RBs into progeny EBs. Progression of this cycle is regulated by three sigma factors, which direct the RNA polymerase to their respective target gene promoters. We hypothesized that the Chlamydia- specific transcriptional regulator GrgA, previously shown to activate σ66 and σ28, plays an essential role in chlamydial development and growth. To test this hypothesis, we applied a novel genetic tool known as dependence on plasmid-mediated expression to create Chlamydia trachomatis with conditional GrgA deficiency. We show that GrgA-deficient C. trachomatis RBs have a growth rate that is approximately half of the normal rate and fail to transition into progeny EBs. In addition, GrgA-deficient C. trachomatis fails to maintain its virulence plasmid. Results of RNA-Seq analysis indicate that GrgA promotes RB growth by optimizing tRNA synthesis and expression of nutrient-acquisition genes, while it enables RB-to-EB conversion by facilitating the expression of a histone and outer membrane proteins required for EB morphogenesis. GrgA also regulates numerous other late genes required for host cell exit and subsequent EB invasion into host cells. Importantly, GrgA stimulates the expression of σ54, the third and last sigma factor, and its activator, AtoC, and thereby indirectly upregulating the expression of σ54-dependent genes. In conclusion, our work demonstrates that GrgA is a master transcriptional regulator in Chlamydia and plays multiple essential roles in chlamydial pathogenicity. IMPORTANCE Hallmarks of the developmental cycle of the obligate intracellular pathogenic bacterium Chlamydia are the primary differentiation of the infectious elementary body (EB) into the proliferative reticulate body (RB) and the secondary differentiation of RBs back into EBs. The mechanisms regulating these transitions remain unclear. In this report, we developed an effective novel strategy termed dependence on plasmid-mediated expression (DOPE) that allows for the knockdown of essential genes in Chlamydia . We demonstrate that GrgA, a Chlamydia -specific transcription factor, is essential for the secondary differentiation and optimal growth of RBs. We also show that GrgA, a chromosome-encoded regulatory protein, controls the maintenance of the chlamydial virulence plasmid. Transcriptomic analysis further indicates that GrgA functions as a critical regulator of all three sigma factors that recognize different promoter sets at developmental stages. The DOPE strategy outlined here should provide a valuable tool for future studies examining chlamydial growth, development, and pathogenicity.

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“…C. trachomatis has a major outer membrane protein (MOMP) that is very diverse. The variation in MOMP in C. trachomatis is used to separate the species into 15 distinct serovars (Shen et al 2024;Wan et al 2023).…”

Section: Introductionmentioning

confidence: 99%

Detection of aac(3)-I gene in Chlamydia trachomatis isolated from conjunctivitis by using PCR technique in Al-Najaf province, Iraq

Al-Buhamrah,

Hussain,

Saadon

2024

MBJ

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Chlamydia trachomatis causes conjunctivitis to spread throughout the world, it infects people of all ages and can cause blindness if not treated properly. Therefore, the current study aimed to diagnose C. trachomatis that causes conjunctivitis and identify the detection of the aac(3)-I gene in C. trachomatis isolated from conjunctivitis by using Polymerase chain reaction (PCR ) technique. One hundred and seven swabs were collected from patients infected with conjunctivitis from different ages (1 month -70 years) and for both sexes (63 samples from females and 44 samples from males) for the period from 27 November till 19 May 2023 from Al-Najaf province in Iraq. Purulent material from the conjunctiva sac was collected on a sterile swab and placed in phosphate-buffered saline and incubated in a deep freezer after completing the collection. All samples were subjected to a PCR to detect the major outer membrane protein (MOMP) gene to diagnose the Chlamydia trachomatis. where the results showed that out of 107 samples, 26 (24.3%) were positive for C. trachomatis. The individuals infected with C. trachomatis were categorised into multiple age groups. The age group ranging from one month to 14 years exhibited the highest prevalence of conjunctivitis. The age group between 15-28 years was followed by the age group between 57-70 years, while the lowest group for conjunctivitis was the age group between 43-56. The existence of the aac(3)-I gene, which confers resistance to the antibiotic gentamicin routinely employed for the treatment of eye infections, was identified. Among the 26 isolates of C. trachomatis, 15 (57.69%) were found to have the aac(3)-I gene. The present investigation demonstrated the significant involvement of C. trachomatis in conjunctivitis, with a higher susceptibility observed among women. The prevalence of conjunctivitis was higher in the age range of 1-28 compared to other age groups. The present investigation exhibited the dissemination of the gentamicin resistant aac(3)-I gene among C. trachomatis bacteria.

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Advances in genetic manipulation of Chlamydia trachomatis

Cited by 4 publications

References 81 publications

Molecular pathogenesis of Chlamydia trachomatis

Molecular pathogenesis of Chlamydia trachomatis

Requirement of GrgA for Chlamydia infectious progeny production, optimal growth, and efficient plasmid maintenance

Detection of aac(3)-I gene in Chlamydia trachomatis isolated from conjunctivitis by using PCR technique in Al-Najaf province, Iraq

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