Comprehensive global genome dynamics of <i>Chlamydia trachomatis</i> show ancient diversification followed by contemporary mixing and recent lineage expansion

Hadfield, James; Harris, Simon R.; Seth-Smith, Helena M. B.; Parmar, Surendra; Andersson, Patiyan; Giffard, Philip M.; Schachter, Julius; Moncada, Jeanne; Ellison, Louise; Vaulet, María Lucía Gallo; Fermepin, Marcelo Rodríguez; Radebe, F; Mendoza, Suyapa; Ouburg, Sander; Morré, Servaas A.; Sachse, Konrad; Puolakkainen, Mirja; Korhonen, Suvi; Sonnex, C; Wiggins, Rebecca; Jalal, Hamid; Brunelli, Tamara; Casprini, Patrizia; Pitt, Rachel; Ison, C; Savicheva, Alevtina; Shipitsyna, Elena; Hadad, Ronza; Kari, László; Burton, Matthew J.; Mabey, David; Solomon, Anthony W.; Lewis, David A.; Marsh, Peter; Unemo, Magnus; Clarke, Ian N.; Parkhill, Julian; Thomson, Nicholas R.

doi:10.1101/gr.212647.116

Cited by 104 publications

(203 citation statements)

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“…Genovar E was highly predominant in our study as reported previously in other studies world‐wide (Gharsallah et al, ; Hadfield et al., ; De Vries et al., ). The conservation of genovar E may be the result of either increased fitness or simply be a stochastic process, reflecting the behavior of the hosts (Hadfield et al., ; Nunes et al., ; Satoh, Ogawa, Saijo, & Ando, ; De Vries et al., ). An expansion of genovar E occurred in Sweden and Europe, due to failure to detect this strain by certain commercial assays.…”

Section: Discussionsupporting

confidence: 90%

“…The variability in the ompA gene has been known for a long time (Frost, Deslandes, Gendron, Bourgaux-Ramoisy, & Bourgaux, 1995;Sturm-Ramirez et al, 2000). A recent study investigating 563 full genome sequences of C. trachomatis reported that the ompA gene experiences the highest rates of recombination in the genome (Hadfield et al, 2017). The presence of mixed infections could be explained by the possibility of recombination and fast diversification of C. trachomatis strains.…”

Section: Comparison Of Genovar Distributions In Tunisian Patients Deter-mentioning

confidence: 99%

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Comparison of reverse hybridization and ompA sequencing methods applied on Chlamydia trachomatis strains from Tunisia

et al. 2017

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Two techniques based on ompA amplification of Chlamydia trachomatis were compared, being reverse hybridization (RHM) and ompA sequencing (OSA), to investigate the concordance between them and to study the epidemiological relevance of each method. In addition, phylogenetic analysis was performed on the ompA sequences. One hundred and seven C. trachomatis positive samples from Tunisian patients and female sex workers were analyzed using both the RHM and ompA sequencing. The overall genovar distribution obtained with both techniques was very similar. The RHM identified nine genovars, being B, D, E, F, G, H, I, J and K, where B, I, J, and K were only found in mixed infections versus 7 types for the OSA being D, E, F, G, H, I, and K. The agreement between both typing techniques was 87.8%. Both methods showed that genovar E was the most predominant type. In 24.3% of the analyzed samples, mixed infections were detected. In 96.1% of these, the genovar identified by OSA was also detected using the RHM. OmpA sequencing allowed determination of six genovar types that could not be typed using RHM. The analyses of ompA nucleotide variation in the 107 clinical specimens detected ompA genovar variants with distinct ompA mutational patterns for types D2, G1, G2, and H1. In conclusion, RHM and OSA showed a high agreement in C. trachomatis genotyping results with each having their specific benefits.

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Section: Discussionsupporting

confidence: 90%

Section: Comparison Of Genovar Distributions In Tunisian Patients Deter-mentioning

confidence: 99%

Comparison of reverse hybridization and ompA sequencing methods applied on Chlamydia trachomatis strains from Tunisia

et al. 2017

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“…These values were derived using different software compared with that used previously (Joseph et al. 2016), hence these cannot be truly compared; the r / m value for C. suis is slightly greater than that seen in the recombinogenic C. trachomatis using the same method (0.31, Hadfield et al. submitted).…”

Section: Resultsmentioning

confidence: 99%

The Chlamydia suis Genome Exhibits High Levels of Diversity, Plasticity, and Mobile Antibiotic Resistance: Comparative Genomics of a Recent Livestock Cohort Shows Influence of Treatment Regimes

Seth-Smith

Wanninger

Bachmann

et al. 2017

Genome Biology and Evolution

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Chlamydia suis is an endemic pig pathogen, belonging to a fascinating genus of obligate intracellular pathogens. Of particular interest, this is the only chlamydial species to have naturally acquired genes encoding for tetracycline resistance. To date, the distribution and mobility of the Tet-island are not well understood. Our study focused on whole genome sequencing of 29 C. suis isolates from a recent porcine cohort within Switzerland, combined with data from USA tetracycline-resistant isolates. Our findings show that the genome of C. suis is very plastic, with unprecedented diversity, highly affected by recombination and plasmid exchange. A large diversity of isolates circulates within Europe, even within individual Swiss farms, suggesting that C. suis originated around Europe. New World isolates have more restricted diversity and appear to derive from European isolates, indicating that historical strain transfers to the United States have occurred. The architecture of the Tet-island is variable, but the tetA(C) gene is always intact, and recombination has been a major factor in its transmission within C. suis. Selective pressure from tetracycline use within pigs leads to a higher number of Tet-island carrying isolates, which appear to be lost in the absence of such pressure, whereas the loss or gain of the Tet-island from individual strains is not observed. The Tet-island appears to be a recent import into the genome of C. suis, with a possible American origin.

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“…Genetic variation in C. trachomatis, a highly prevalent bacterial STI [7], has historically been considered uncommon. However, a recent large-scale genomic analysis of geographically and temporally diverse C. trachomatis strains revealed a remarkable degree of homologous recombination and mutations that have occurred in the organism in the recent millennia [8].…”

Section: Discussionmentioning

confidence: 99%

Validation of an Aptima-format Finnish new variant of Chlamydia trachomatis (FI-nvCT) surveillance assay, 2019

et al. 2020

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The Finnish new variant of Chlamydia trachomatis (FI-nvCT) is escaping diagnostics in Finland, Norway and Sweden. We have developed and validated an Aptima-format nucleic acid amplification test (NAAT) designed specifically to detect the FI-nvCT. This NAAT has high sensitivity (100%) and specificity (100%) for the FI-nvCT strain, enabling further investigation of the geographic distribution, prevalence and transmission of this diagnostic-escape mutant in screening populations in Europe.In February 2019, investigation of discrepant nucleic acid amplification test (NAAT) results led to the discovery of a new genetic variant strain of Chlamydia trachomatis in south-western Finland [1]. This strain, designated Finnish new variant of C. trachomatis (FI-nvCT), harbours a single nt base mutation (C1515T; Escherichia coli numbering) in 23S rRNA. This mutation was determined to be the root cause for compromised detection of the organism by the Aptima Combo 2 (AC2) diagnostic test (Hologic Inc., San Diego, California, United States (US)), which targets C. trachomatis 23S rRNA [2,3]. Archived and newly received clinical specimens in Finland and Sweden with equivocal results or high-negative relative light units (RLU) from 15 to 99 in the AC2 test, and discrepant results between AC2 (target: 23S rRNA) and the separate Aptima Chlamydia trachomatis (ACT) test (target: 16S rRNA) (i.e. AC2 negative/equivocal-ACT positive) signalled the presence of the new strain. Data collected in subsequent investigations suggested a recent emergence of FI-nvCT in south-western Finland, Norway and Sweden with relatively low prevalence (ca 1-6%) among patients with C. trachomatis infections [1,3-5]. We have developed and validated a research-use only Aptima-format surveillance NAAT designed specifically to detect the FI-nvCT strain. This assay should facilitate further investigations to determine the geographic distribution, prevalence and transmission of this diagnostic-escape mutant. New Aptima-format surveillance assay for the Finnish new variant of Chlamydia trachomatisTo understand the geographic distribution, prevalence and transmission dynamics of the FI-nvCT strain nationally and internationally, we have developed an Aptima-format NAAT that sensitively and specifically detects FI-nvCT (23S rRNA gene C1515T mutation) but not wild-type (C1515) C. trachomatis strains. This research-use only test uses target capture and transcription-mediated amplification chemistries on the automated Panther instrument (Hologic Inc.) to isolate and amplify C. trachomatis 23S rRNA, and an acridinium ester probe to selectively detect the C→T mutation at position 1515. Validation and verification results for the Aptima-format surveillance assay for the Finnish new variant of C. trachomatisAll validation and verification studies of the new FI-nvCT assay were conducted according to Clinical Laboratory Standards Institute (CLSI) standard protocols used for in vitro diagnostic assay validation [6]. The cut-off value of the test (100,000 RLU) was initially establis...

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Comprehensive global genome dynamics of Chlamydia trachomatis show ancient diversification followed by contemporary mixing and recent lineage expansion

Cited by 104 publications

References 50 publications

Comparison of reverse hybridization and ompA sequencing methods applied on Chlamydia trachomatis strains from Tunisia

Comparison of reverse hybridization and ompA sequencing methods applied on Chlamydia trachomatis strains from Tunisia

The Chlamydia suis Genome Exhibits High Levels of Diversity, Plasticity, and Mobile Antibiotic Resistance: Comparative Genomics of a Recent Livestock Cohort Shows Influence of Treatment Regimes

Validation of an Aptima-format Finnish new variant of Chlamydia trachomatis (FI-nvCT) surveillance assay, 2019

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