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Genomic factors related to tissue tropism in Chlamydia pneumoniae infection.

Weinmaier T, Hoser J, Eck S, Kaufhold I, Shima K, Strom TM, Rattei T, Rupp J - BMC Genomics (2015)

Bottom Line: Although of significant clinical relevance, complete genome sequences of only four clinical Cpn strains have been obtained.In one of these, clinical isolates from coronary arteries and blood monocytes were closely grouped together.This study substantially expands the genomic data of Cpn and elucidates its evolutionary history.

View Article: PubMed Central - PubMed

Affiliation: Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, University of Vienna, 1090, Vienna, Austria. Thomas.Weinmaier@univie.ac.at.

ABSTRACT

Background: Chlamydia pneumoniae (Cpn) are obligate intracellular bacteria that cause acute infections of the upper and lower respiratory tract and have been implicated in chronic inflammatory diseases. Although of significant clinical relevance, complete genome sequences of only four clinical Cpn strains have been obtained. All of them were isolated from the respiratory tract and shared more than 99% sequence identity. Here we investigate genetic differences on the whole-genome level that are related to Cpn tissue tropism and pathogenicity.

Results: We have sequenced the genomes of 18 clinical isolates from different anatomical sites (e.g. lung, blood, coronary arteries) of diseased patients, and one animal isolate. In total 1,363 SNP loci and 184 InDels have been identified in the genomes of all clinical Cpn isolates. These are distributed throughout the whole chlamydial genome and enriched in highly variable regions. The genomes show clear evidence of recombination in at least one potential region but no phage insertions. The tyrP gene was always encoded as single copy in all vascular isolates. Phylogenetic reconstruction revealed distinct evolutionary lineages containing primarily non-respiratory Cpn isolates. In one of these, clinical isolates from coronary arteries and blood monocytes were closely grouped together. They could be distinguished from all other isolates by characteristic nsSNPs in genes involved in RB to EB transition, inclusion membrane formation, bacterial stress response and metabolism.

Conclusions: This study substantially expands the genomic data of Cpn and elucidates its evolutionary history. The translation of the observed Cpn genetic differences into biological functions and the prediction of novel pathogen-oriented diagnostic strategies have to be further explored.

No MeSH data available.


Related in: MedlinePlus

Whole genome recombination tree. The split graph obtained from the SNPs between all human Cpn isolates and the frog isolate DC9. It contains a split that clearly separates the isolates CM1 and J138 from TW183 and UZG1 and the group consisting of Wien1, U1271, CWL029, K7, MUL2216, Wien3, CV15, PB1, PB2, Wien2, CWL011, CV14, H12, Panola and CWL029c.
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Fig2: Whole genome recombination tree. The split graph obtained from the SNPs between all human Cpn isolates and the frog isolate DC9. It contains a split that clearly separates the isolates CM1 and J138 from TW183 and UZG1 and the group consisting of Wien1, U1271, CWL029, K7, MUL2216, Wien3, CV15, PB1, PB2, Wien2, CWL011, CV14, H12, Panola and CWL029c.

Mentions: Genome recombination has been proposed but could not be shown in Cpn so far [11-13]. As our study significantly expands the number of Cpn genome sequences, it is now feasible to address the question of recombination. From a multiple genome alignment also containing DC9 as closest representative of non-human isolates, we determined a total number of 4,690 SNP loci. A statistical Phi test and a Bayesian inference approach yielded significant evidence that recombination has occurred between the isolates (p-value < 1e-05). Recombination was observed between human, but not between human and the non-human isolate (FigureĀ 2 and Additional file 3). Testing sliding windows along the genome alignment suggests two regions of recombination, one between the genomic positions 10 Kb and 40 Kb and the second between 1 Mb and 1.07 Mb (Additional file 1: Table S7a and Additional file 4). The areas adjacent to the two regions of recombination did not show evidence for recombination. This suggests an exchange of DNA within these two relatively short genomic regions. Due to the limited number of SNPs the actual recombination sites cannot be determined more precisely. The first region contains 7 pmp-genes of which 6 are annotated as pseudogenes (Additional file 1: Table S7b). The second region is enclosed by the operon of ribosomal RNAs and three ribosomal proteins whereas the genes in between encode various different enzymes (Additional file 1: Table S7c).Figure 2


Genomic factors related to tissue tropism in Chlamydia pneumoniae infection.

Weinmaier T, Hoser J, Eck S, Kaufhold I, Shima K, Strom TM, Rattei T, Rupp J - BMC Genomics (2015)

Whole genome recombination tree. The split graph obtained from the SNPs between all human Cpn isolates and the frog isolate DC9. It contains a split that clearly separates the isolates CM1 and J138 from TW183 and UZG1 and the group consisting of Wien1, U1271, CWL029, K7, MUL2216, Wien3, CV15, PB1, PB2, Wien2, CWL011, CV14, H12, Panola and CWL029c.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4489044&req=5

Fig2: Whole genome recombination tree. The split graph obtained from the SNPs between all human Cpn isolates and the frog isolate DC9. It contains a split that clearly separates the isolates CM1 and J138 from TW183 and UZG1 and the group consisting of Wien1, U1271, CWL029, K7, MUL2216, Wien3, CV15, PB1, PB2, Wien2, CWL011, CV14, H12, Panola and CWL029c.
Mentions: Genome recombination has been proposed but could not be shown in Cpn so far [11-13]. As our study significantly expands the number of Cpn genome sequences, it is now feasible to address the question of recombination. From a multiple genome alignment also containing DC9 as closest representative of non-human isolates, we determined a total number of 4,690 SNP loci. A statistical Phi test and a Bayesian inference approach yielded significant evidence that recombination has occurred between the isolates (p-value < 1e-05). Recombination was observed between human, but not between human and the non-human isolate (FigureĀ 2 and Additional file 3). Testing sliding windows along the genome alignment suggests two regions of recombination, one between the genomic positions 10 Kb and 40 Kb and the second between 1 Mb and 1.07 Mb (Additional file 1: Table S7a and Additional file 4). The areas adjacent to the two regions of recombination did not show evidence for recombination. This suggests an exchange of DNA within these two relatively short genomic regions. Due to the limited number of SNPs the actual recombination sites cannot be determined more precisely. The first region contains 7 pmp-genes of which 6 are annotated as pseudogenes (Additional file 1: Table S7b). The second region is enclosed by the operon of ribosomal RNAs and three ribosomal proteins whereas the genes in between encode various different enzymes (Additional file 1: Table S7c).Figure 2

Bottom Line: Although of significant clinical relevance, complete genome sequences of only four clinical Cpn strains have been obtained.In one of these, clinical isolates from coronary arteries and blood monocytes were closely grouped together.This study substantially expands the genomic data of Cpn and elucidates its evolutionary history.

View Article: PubMed Central - PubMed

Affiliation: Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, University of Vienna, 1090, Vienna, Austria. Thomas.Weinmaier@univie.ac.at.

ABSTRACT

Background: Chlamydia pneumoniae (Cpn) are obligate intracellular bacteria that cause acute infections of the upper and lower respiratory tract and have been implicated in chronic inflammatory diseases. Although of significant clinical relevance, complete genome sequences of only four clinical Cpn strains have been obtained. All of them were isolated from the respiratory tract and shared more than 99% sequence identity. Here we investigate genetic differences on the whole-genome level that are related to Cpn tissue tropism and pathogenicity.

Results: We have sequenced the genomes of 18 clinical isolates from different anatomical sites (e.g. lung, blood, coronary arteries) of diseased patients, and one animal isolate. In total 1,363 SNP loci and 184 InDels have been identified in the genomes of all clinical Cpn isolates. These are distributed throughout the whole chlamydial genome and enriched in highly variable regions. The genomes show clear evidence of recombination in at least one potential region but no phage insertions. The tyrP gene was always encoded as single copy in all vascular isolates. Phylogenetic reconstruction revealed distinct evolutionary lineages containing primarily non-respiratory Cpn isolates. In one of these, clinical isolates from coronary arteries and blood monocytes were closely grouped together. They could be distinguished from all other isolates by characteristic nsSNPs in genes involved in RB to EB transition, inclusion membrane formation, bacterial stress response and metabolism.

Conclusions: This study substantially expands the genomic data of Cpn and elucidates its evolutionary history. The translation of the observed Cpn genetic differences into biological functions and the prediction of novel pathogen-oriented diagnostic strategies have to be further explored.

No MeSH data available.


Related in: MedlinePlus