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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.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.

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

Single nucleotide polymorphism phylogeny. Maximum likelihood phylogenetic tree based on SNPs derived from a whole genome alignment. Diamonds on the tree branches indicate bootstrap support > 80. Colors on the right of the tree represent (A) the type of tissue: blue: conjunctival, green: respiratory, red: vascular; (B) country of origin; dark green: Taiwan, green: Belgium, dark blue: USA, light blue: Japan, yellow: Germany, orange: Austria; (C) year of isolation: dark red: 1965, light green: before 1996, orange: before 1992, green: 1983, purple: 1994, white: NA, light red: 1987, dark green: 1998–1999, light blue: 2001, dark blue: 2002, olive: 1998; (D)tyrP coverage: the gray scale of the tyrP coverage indicates the estimated tyrP copy number from one copy (white) to two copies (dark gray).
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Fig3: Single nucleotide polymorphism phylogeny. Maximum likelihood phylogenetic tree based on SNPs derived from a whole genome alignment. Diamonds on the tree branches indicate bootstrap support > 80. Colors on the right of the tree represent (A) the type of tissue: blue: conjunctival, green: respiratory, red: vascular; (B) country of origin; dark green: Taiwan, green: Belgium, dark blue: USA, light blue: Japan, yellow: Germany, orange: Austria; (C) year of isolation: dark red: 1965, light green: before 1996, orange: before 1992, green: 1983, purple: 1994, white: NA, light red: 1987, dark green: 1998–1999, light blue: 2001, dark blue: 2002, olive: 1998; (D)tyrP coverage: the gray scale of the tyrP coverage indicates the estimated tyrP copy number from one copy (white) to two copies (dark gray).

Mentions: The most stable tree was obtained from all SNP positions, including non-synonymous, synonymous, non-coding and intergenic loci (Figure 3). The tree shows a clear separation between outgroups, DC9 from frog and the koala isolate LPCoLN, and the human isolates. The human isolates split up into three clusters, all supported by high bootstrap values. TW183 and UZG1 form one cluster that branches deeper in the tree than the other two human clusters. The isolates YK41, AR39, GiD and J138 are contained in another cluster together with CM1, which is located in a sister branch within this cluster. The long sub-branch of J138 can be mainly ascribed to a region between genomic positions 1,204,000 and 1,205,000, showing around 110 SNPs that are only present in J138. In J138 no gene is annotated in this region, whereas it is marked as pseudogene CpB1096 in TW138 and contains an annotated gene (CPn_1054) in CWL029. The third cluster contains three sub-groups, all of which are well supported by bootstrap values. The first group consists of H12, Panola and K7; the isolates U1271, CWL011, CWL029 and CWL029c form the second group. The largest sub-group in the branch consists of the isolates Wien2, Wien3, MUL2216, CV15, Wien1, CV14, PB1 and PB2. Inside this sub-group there are again three small groups, the first containing Wien2 and Wien3, the second containing MUL2216 and CV15 and the third consisting of Wien1, CV14, PB1 and PB2. All of these three groups have good bootstrap support. Overall, there is a remarkable congruence between the phylogenetic tree presented in this study and the phylogeny calculated from a set of selected SNP positions reported in an earlier study from Rattei et al. [12], with our new phylogeny providing a much higher resolution of the CWL029 containing cluster. The topology of this tree, based on all SNPs, is also supported by trees based on subsets of SNPs, such as from 31 phylogenetic marker genes (Additional file 5 A) and from 545 genes that represent the chlamydial pan-genome (Additional file 5 B).Figure 3


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)

Single nucleotide polymorphism phylogeny. Maximum likelihood phylogenetic tree based on SNPs derived from a whole genome alignment. Diamonds on the tree branches indicate bootstrap support > 80. Colors on the right of the tree represent (A) the type of tissue: blue: conjunctival, green: respiratory, red: vascular; (B) country of origin; dark green: Taiwan, green: Belgium, dark blue: USA, light blue: Japan, yellow: Germany, orange: Austria; (C) year of isolation: dark red: 1965, light green: before 1996, orange: before 1992, green: 1983, purple: 1994, white: NA, light red: 1987, dark green: 1998–1999, light blue: 2001, dark blue: 2002, olive: 1998; (D)tyrP coverage: the gray scale of the tyrP coverage indicates the estimated tyrP copy number from one copy (white) to two copies (dark gray).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Single nucleotide polymorphism phylogeny. Maximum likelihood phylogenetic tree based on SNPs derived from a whole genome alignment. Diamonds on the tree branches indicate bootstrap support > 80. Colors on the right of the tree represent (A) the type of tissue: blue: conjunctival, green: respiratory, red: vascular; (B) country of origin; dark green: Taiwan, green: Belgium, dark blue: USA, light blue: Japan, yellow: Germany, orange: Austria; (C) year of isolation: dark red: 1965, light green: before 1996, orange: before 1992, green: 1983, purple: 1994, white: NA, light red: 1987, dark green: 1998–1999, light blue: 2001, dark blue: 2002, olive: 1998; (D)tyrP coverage: the gray scale of the tyrP coverage indicates the estimated tyrP copy number from one copy (white) to two copies (dark gray).
Mentions: The most stable tree was obtained from all SNP positions, including non-synonymous, synonymous, non-coding and intergenic loci (Figure 3). The tree shows a clear separation between outgroups, DC9 from frog and the koala isolate LPCoLN, and the human isolates. The human isolates split up into three clusters, all supported by high bootstrap values. TW183 and UZG1 form one cluster that branches deeper in the tree than the other two human clusters. The isolates YK41, AR39, GiD and J138 are contained in another cluster together with CM1, which is located in a sister branch within this cluster. The long sub-branch of J138 can be mainly ascribed to a region between genomic positions 1,204,000 and 1,205,000, showing around 110 SNPs that are only present in J138. In J138 no gene is annotated in this region, whereas it is marked as pseudogene CpB1096 in TW138 and contains an annotated gene (CPn_1054) in CWL029. The third cluster contains three sub-groups, all of which are well supported by bootstrap values. The first group consists of H12, Panola and K7; the isolates U1271, CWL011, CWL029 and CWL029c form the second group. The largest sub-group in the branch consists of the isolates Wien2, Wien3, MUL2216, CV15, Wien1, CV14, PB1 and PB2. Inside this sub-group there are again three small groups, the first containing Wien2 and Wien3, the second containing MUL2216 and CV15 and the third consisting of Wien1, CV14, PB1 and PB2. All of these three groups have good bootstrap support. Overall, there is a remarkable congruence between the phylogenetic tree presented in this study and the phylogeny calculated from a set of selected SNP positions reported in an earlier study from Rattei et al. [12], with our new phylogeny providing a much higher resolution of the CWL029 containing cluster. The topology of this tree, based on all SNPs, is also supported by trees based on subsets of SNPs, such as from 31 phylogenetic marker genes (Additional file 5 A) and from 545 genes that represent the chlamydial pan-genome (Additional file 5 B).Figure 3

Bottom Line: Although of significant clinical relevance, complete genome sequences of only four clinical Cpn strains have been obtained.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.

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