Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain

Seth-Smith, Helena M. B.; Harris, Simon R.; Persson, Kenneth; Marsh, Pete; Barron, Andrew R.; Bignell, Alexandra; Bjartling, Carina; Clark, Louise; Cutcliffe, Lesley T.; Lambden, Paul R.; Lennard, Nicola; Lockey, Sarah J; Quail, Michael A.; Salim, Omar; Skilton, Rachel J.; Wang, Yibing; Holland, Martin J.; Parkhill, Julian; Thomson, Nicholas R.; Clarke, Ian N.

doi:10.1186/1471-2164-10-239

Cited by 123 publications

(169 citation statements)

References 45 publications

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“…Chlamydia trachomatis Sweden 2 (E/SW2), representing the Swedish nvCT (plasmid‐containing serovar E, with a 377‐base pair deletion in CDS1), was isolated from a male urethra in Malmö in 2006 (Seth‐Smith et al ., 2009; Unemo et al ., 2010). Chlamydia trachomatis Sweden, serovar F, plasmid‐free (F/SWFP−) is a cervical isolate from Malmö, Sweden, in 1995 (Persson et al ., 1996; Wang et al ., 2012).…”

Section: Methodsmentioning

confidence: 99%

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Plasmid deficiency in urogenital isolates ofChlamydia trachomatisreduces infectivity and virulence in a mouse model

et al. 2013

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We hypothesized that the plasmid of urogenital isolates of Chlamydia trachomatis would modulate infectivity and virulence in a mouse model. To test this hypothesis, we infected female mice in the respiratory or urogenital tract with graded doses of a human urogenital isolate of C. trachomatis, serovar F, possessing the cognate plasmid. For comparison, we inoculated mice with a plasmid‐free serovar F isolate. Following urogenital inoculation, the plasmid‐free isolate displayed significantly reduced infectivity compared with the wild‐type strain with the latter yielding a 17‐fold lower infectious dose to yield 50% infection. When inoculated via the respiratory tract, the plasmid‐free isolate exhibited reduced infectivity and virulence (as measured by weight change) when compared to the wild‐type isolate. Further, differences in infectivity, but not in virulence were observed in a C. trachomatis, serovar E isolate with a deletion within the plasmid coding sequence 1 when compared to a serovar E isolate with no mutations in the plasmid. We conclude that plasmid loss reduces virulence and infectivity in this mouse model. These findings further support a role for the chlamydial plasmid in infectivity and virulence in vivo.

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Section: Methodsmentioning

confidence: 99%

“…Extraction of DNA was performed on strain F/SWFP− as previously described (Seth‐Smith et al ., 2009). DNA was sequenced on the Illumina GAII platform using 54‐bp paired‐end reads, resulting in a mean genome coverage of 1527 ×.…”

Section: Methodsmentioning

confidence: 99%

Plasmid deficiency in urogenital isolates ofChlamydia trachomatisreduces infectivity and virulence in a mouse model

et al. 2013

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“…For example, the plasmid p2TK2-SW2 (20) and the pBOMB4 series of plasmids (21) combined a ␤-lactamase-encoding gene (bla) and a multiple-cloning site into the L2 pSW2 and pL2 (L2/434/Bu) plasmids, respectively. The pBOMB4 series offers the additional benefit of utilizing an intact L2 plasmid (pL2) rather than the SW2 variant plasmid, which harbors a 377-bp deletion in CDS1 (148). These vectors are well suited for expressing epitope-tagged or untagged gene products under the control of native promoters.…”

Section: Ectopic Gene Expressionmentioning

confidence: 99%

“…Stable transformants lost their endogenous plasmid and expressed both the ␤-lactamase and chloramphenicol acetyltransferase genes, indicating that the standard E. coli promoters driving the expression of both drug resistance cassettes are functional in C. trachomatis. Subsequently, EBs were transformed with the hybrid shuttle plasmid pGFP::SW2, which consists of a variant L2 plasmid (pSW2) with a 377-bp deletion in CDS1, isolated from a Swedish LGV L2 clinical isolate (148), and an E. coli plasmid expressing ␤-lactamase and GFP fused to chloramphenicol acetyltransferase under the control of a Neisseria promoter. GFP-expressing bacteria within inclusions were readily detectable (19).…”

Section: Stable Plasmid Transformationmentioning

confidence: 99%

Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen

Bastidas

Valdivia

2016

Microbiol Mol Biol Rev

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SUMMARYChlamydiaspecies infect millions of individuals worldwide and are important etiological agents of sexually transmitted disease, infertility, and blinding trachoma. Historically, the genetic intractability of this intracellular pathogen has hindered the molecular dissection of virulence factors contributing to its pathogenesis. The obligate intracellular life cycle ofChlamydiaand restrictions on the use of antibiotics as selectable markers have impeded the development of molecular tools to genetically manipulate these pathogens. However, recent developments in the field have resulted in significant gains in our ability to alter the genome ofChlamydia, which will expedite the elucidation of virulence mechanisms. In this review, we discuss the challenges affecting the development of molecular genetic tools forChlamydiaand the work that laid the foundation for recent advancements in the genetic analysis of this recalcitrant pathogen.

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“…35 It is also known that the plasmid is not naturally transferred readily between clinical isolates supporting a host-plasmid tropism relationship. 36 This has been confirmed by recent experiments aimed at developing a transformation system for non-LGV isolates of the ocular tropic C. trachomatis serovar A where it was observed that stable plasmid transformants were only obtained when the transforming plasmid shuttle vector was matched with the parental strain. 37 More recently, transcriptional profiling of cultured human epithelial cells infected with plasmid-deficient and -proficient C. trachomatis organisms has revealed statistically significant increases in the levels of expression of host genes coding for proinflammatory, immune suppression, and cell growth and fibrosis proteins in plasmid-bearing strains.…”

Section: Chlamydial Plasmidmentioning

confidence: 52%

Development of a vaccine for Chlamydia trachomatis: challenges and current progress

Hafner¹

2015

VDT

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Abstract:Chlamydia trachomatis remains an enigmatic bacterial pathogen with no vaccine yet available to treat human ocular and genital tract infections caused by tissue-tropic serovars of the organism. Globally, it is the leading cause of preventable blindness as well as the leading cause of bacterial sexually transmitted infections. The pathogen has a range of virulence factors that enable it to successfully evade both the innate and adaptive immune system of the host. The host immune system, although protective, paradoxically is also associated closely with the pathologies of trachoma and pelvic inflammatory disease -disease sequelae of some chlamydial infections and reinfections in some genetically susceptible hosts. In this review, we focus on what is known currently about the pathogenesis of ocular and genital infections caused by this mucosal pathogen. We also discuss novel insights into the pathogenesis of infections caused by the genital and ocular serovars of C. trachomatis, including a discussion of both pathogen and host factors, such as the human microbiota at these mucosal sites as well as the current immunological challenges facing vaccine development. Finally, we discuss the current progress toward development of a vaccine against C. trachomatis. A wide range of recombinant protein antigens are being identified and, hence, are available for vaccine trials. A plasmid-free live strain has recently been produced and evaluated in the mouse (Chlamydia muridarum) and monkey (C. trachomatis) models. The data for ocular infections in the monkey model was particularly encouraging, although the path to regulatory approval of a live vaccine is still uncertain. While still a major challenge, vaccines for ocular and genital C. trachomatis infections are looking more promising.

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Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain

Cited by 123 publications

References 45 publications

Plasmid deficiency in urogenital isolates ofChlamydia trachomatisreduces infectivity and virulence in a mouse model

Plasmid deficiency in urogenital isolates ofChlamydia trachomatisreduces infectivity and virulence in a mouse model

Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen

Development of a vaccine for Chlamydia trachomatis: challenges and current progress

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