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Mosaic structure of intragenic repetitive elements in histone H1-like protein Hc2 varies within serovars of Chlamydia trachomatis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology. (Björn Herrmann)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organism Biology, Systematic Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
University of Aarhus. (Department of Medical Microbiology and Immunology)
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2010 (English)In: BMC Microbiology, ISSN 1471-2180, Vol. 10, 81- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The histone-like protein Hc2 binds DNA in Chlamydia trachomatis and is known to vary in size between 165 and 237 amino acids, which is caused by different numbers of lysine-rich pentamers. A more complex structure was seen in this study when sequences from 378 specimens covering the hctB gene, which encodes Hc2, were compared. RESULTS: This study shows that the size variation is due to different numbers of 36-amino acid long repetitive elements built up of five pentamers and one hexamer. Deletions and amino acid substitutions result in 14 variants of repetitive elements and these elements are combined into 22 configurations. A protein with similar structure has been described in Bordetella but was now also found in other genera, including Burkholderia, Herminiimonas, Minibacterium and Ralstonia.Sequence determination resulted in 41 hctB variants that formed four clades in phylogenetic analysis. Strains causing the eye disease trachoma and strains causing invasive lymphogranuloma venereum infections formed separate clades, while strains from urogenital infections were more heterogeneous. Three cases of recombination were identified. The size variation of Hc2 has previously been attributed to deletions of pentamers but we show that the structure is more complex with both duplication and deletions of 36-amino acid long elements. CONCLUSIONS: The polymorphisms in Hc2 need to be further investigated in experimental studies since DNA binding is essential for the unique biphasic life cycle of the Chlamydiacae. The high sequence variation in the corresponding hctB gene enables phylogenetic analysis and provides a suitable target for the genotyping of C. trachomatis.

Place, publisher, year, edition, pages
BioMed Central , 2010. Vol. 10, 81- p.
National Category
Microbiology in the medical area
Research subject
Clinical Bacteriology
Identifiers
URN: urn:nbn:se:uu:diva-108948DOI: 10.1186/1471-2180-10-81ISI: 000276396900001PubMedID: 20236532OAI: oai:DiVA.org:uu-108948DiVA: diva2:241679
Available from: 2009-10-05 Created: 2009-10-05 Last updated: 2011-01-18Bibliographically approved
In thesis
1. Chlamydia trachomatis: Development of molecular typing methods and applications in epidemiology
Open this publication in new window or tab >>Chlamydia trachomatis: Development of molecular typing methods and applications in epidemiology
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A general aim was to combine molecular typing methods with clinical background information to increase epidemiological knowledge about Chlamydia trachomatis infections.

An outbreak of Lymfogranuloma venereum (LGV), caused by a more invasive variant of C. trachomatis, was reported from the Netherlands in 2003 among men who have sex with men (MSM). All Chlamydia positive specimens from a venereal disease clinic for MSM in Stockholm during one year were genotyped. No spread of LGV was found, apart from three symptomatic cases. The same ompA genotypes were found among MSM in Melbourne, but the genotype distribution was different compared to findings among the heterosexual population in Sweden.

The standard method for genotyping of Chlamydia is ompA-sequencing, but it has low resolution because one genotype predominates. A multilocus sequence typing (MLST) system based on five targets was developed. In a sample of 47 specimens, 32 variants were found with MLST, but only 12 variants with ompA-sequencing. The polymorphisms in the hctB gene, one MLST target, are caused by an element of 108 bp that is present in two to four repetitions and in different variants. Although the DNA-binding function of Hc2 that is encoded by hctB has been studied, our findings of a considerable size variation show that new studies are needed.

In 2006, specimens with a 377 bp deletion in the cryptic plasmid covering the target region for diagnostic test systems from Abbott and Roche were discovered in Sweden. Applying MLST to these specimens indicated that there was a single clone, denoted nvCT. The proportion of nvCT in all detected Chlamydia cases was higher (20% to 65%) in counties using Abbott/Roche compared to counties using the BectonDickinson test system (7% to 20%). The proportions of nvCT converge in counties with high or low levels when detection systems were adjusted to detect nvCT.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 71 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 488
Keyword
Chlamydia trachomatis, Lymphogranuloma venereum, Genotyping, MLST, nvCT, hctB, Hc2
National Category
Microbiology in the medical area
Research subject
Clinical Bacteriology
Identifiers
urn:nbn:se:uu:diva-108930 (URN)978-91-554-7625-0 (ISBN)
Public defence
2009-11-20, Hörsalen, Klinisk Mikrobiologi, Akademiska Sjukhuset, Dag Hammarskjöldsväg 17, Uppsala, 09:15 (English)
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Available from: 2009-10-30 Created: 2009-10-05 Last updated: 2009-10-30Bibliographically approved

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Klint, MarkusThollesson, MikaelBongcam-Rudloff, ErikHerrmann, Björn

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