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Predicting phenotype and emerging strains among Chlamydia trachomatis infections.

Dean D, Bruno WJ, Wan R, Gomes JP, Devignot S, Mehari T, de Vries HJ, Morré SA, Myers G, Read TD, Spratt BG - Emerging Infect. Dis. (2009)

Bottom Line: Twenty-nine of 52 alleles had nonuniform distributions of frequencies across regions (p<0.001).Recombinant strains were observed among STI clusters.Single nucleotide polymorphisms (SNPs) were predictive of disease specificity.

View Article: PubMed Central - PubMed

Affiliation: Children's Global Health Initiativ, Children's Hospital Oakland Research Institute, Oakland, California 94609, USA. ddean@chori.org

ABSTRACT
Chlamydia trachomatis is a global cause of blinding trachoma and sexually transmitted infections (STIs). We used comparative genomics of the family Chlamydiaceae to select conserved housekeeping genes for C. trachomatis multilocus sequencing, characterizing 19 reference and 68 clinical isolates from 6 continental/subcontinental regions. There were 44 sequence types (ST). Identical STs for STI isolates were recovered from different regions, whereas STs for trachoma isolates were restricted by continent. Twenty-nine of 52 alleles had nonuniform distributions of frequencies across regions (p<0.001). Phylogenetic analysis showed 3 disease clusters: invasive lymphogranuloma venereum strains, globally prevalent noninvasive STI strains (ompA genotypes D/Da, E, and F), and nonprevalent STI strains with a trachoma subcluster. Recombinant strains were observed among STI clusters. Single nucleotide polymorphisms (SNPs) were predictive of disease specificity. Multilocus and SNP typing can now be used to detect diverse and emerging C. trachomatis strains for epidemiologic and evolutionary studies of trachoma and STI populations worldwide.

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Related in: MedlinePlus

Comparison of 14 housekeeping genes among genome sequences of 4 Chlamydiaceae species and 7 strains. Circle 1, genes on forward Chlamydia trachomatis strand, color coded by role category; Circle 2, genes on reverse C. trachomatis strand; Circle 3, multilocus sequence typing (MLST) candidates, C. trachomatis; Circle 4, MLST candidates, C. pneumoniae AR39; Circle 5, MLST candidates, C. caviae (GPIC); Circle 6, MLST candidates, C. muridarum (MoPn). Colors in circles 3, 4, 5 and 6 are consistent for each gene across genomes i.e., “blue” gene in each circle is ortholog in that genome for “blue” gene in C. trachomatis. Blue, glyA, serine hydroxymethyl-transferase; red, tryptophanyl-tRNA synthetase; yellow, mdhC, malate dehydrogenase; green, V-type ATPase, subunit A; cyan, pdhA, pyruvate dehydrogenase; black, GTP-binding protein lepa; magenta, transcription termination factor rho; brown, yhbG, probable ABC transporter ATP-binding protein; orange, pykF, pyruvate kinase; olive green, conserved hypothetical protein; gray, acetyl-CoA carboxylase beta subunit; pink, threonyl-tRNA synthetase; violet, lysS, lysyl-tRNA synthetase; light green, leuS, leucyl-tRNA synthetase. Those denoted in boldface above were used for C. trachomatis MLST. ompA gene location is shown for C. trachomatis (dark green).
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Figure 1: Comparison of 14 housekeeping genes among genome sequences of 4 Chlamydiaceae species and 7 strains. Circle 1, genes on forward Chlamydia trachomatis strand, color coded by role category; Circle 2, genes on reverse C. trachomatis strand; Circle 3, multilocus sequence typing (MLST) candidates, C. trachomatis; Circle 4, MLST candidates, C. pneumoniae AR39; Circle 5, MLST candidates, C. caviae (GPIC); Circle 6, MLST candidates, C. muridarum (MoPn). Colors in circles 3, 4, 5 and 6 are consistent for each gene across genomes i.e., “blue” gene in each circle is ortholog in that genome for “blue” gene in C. trachomatis. Blue, glyA, serine hydroxymethyl-transferase; red, tryptophanyl-tRNA synthetase; yellow, mdhC, malate dehydrogenase; green, V-type ATPase, subunit A; cyan, pdhA, pyruvate dehydrogenase; black, GTP-binding protein lepa; magenta, transcription termination factor rho; brown, yhbG, probable ABC transporter ATP-binding protein; orange, pykF, pyruvate kinase; olive green, conserved hypothetical protein; gray, acetyl-CoA carboxylase beta subunit; pink, threonyl-tRNA synthetase; violet, lysS, lysyl-tRNA synthetase; light green, leuS, leucyl-tRNA synthetase. Those denoted in boldface above were used for C. trachomatis MLST. ompA gene location is shown for C. trachomatis (dark green).

Mentions: We genome-sequenced 7 strains from 4 species of the 2 genera of Chlamydiaceae: C. trachomatis (strains D/UW-3/CX [18] and A/Har-13 [19]), Chlamydia muridarum (rodent strain MoPn [20]), Chlamydophila pneumoniae (human strains AR39 [20]; CWL029 [21], and J138 [21]), and Chlamydophila caviae (guinea pig inclusion conjunctivitis strain [22]), the most distantly related species of Chlamydiaceae. On the basis of comparative genomics (20) and comparisons generated by CGView (23), we identified an initial candidate pool of 14 housekeeping genes (Figure 1) present in all 7 genomes with an average BLAST score ratio (BSR) (24) >0.5 for orthologs queried against C. caviae relative to the BLAST score of each sequence against itself. The BSR of >0.5 provides a cutoff to select genes that have lower levels of nucleotide sequence divergence in the genome (i.e., putative housekeeping genes). We then selected 7 genes (Figure 1) on the basis of i) diverse chromosomal regions where a single recombinational exchange would be unlikely to co-introduce >1 selected gene; ii) regions where several contiguous genes were involved in metabolic or key functions; iii) essential metabolic enzymes (e.g., tRNA synthases); iv) genes without similarity to human genes; and v) no genes under diversifying selection.


Predicting phenotype and emerging strains among Chlamydia trachomatis infections.

Dean D, Bruno WJ, Wan R, Gomes JP, Devignot S, Mehari T, de Vries HJ, Morré SA, Myers G, Read TD, Spratt BG - Emerging Infect. Dis. (2009)

Comparison of 14 housekeeping genes among genome sequences of 4 Chlamydiaceae species and 7 strains. Circle 1, genes on forward Chlamydia trachomatis strand, color coded by role category; Circle 2, genes on reverse C. trachomatis strand; Circle 3, multilocus sequence typing (MLST) candidates, C. trachomatis; Circle 4, MLST candidates, C. pneumoniae AR39; Circle 5, MLST candidates, C. caviae (GPIC); Circle 6, MLST candidates, C. muridarum (MoPn). Colors in circles 3, 4, 5 and 6 are consistent for each gene across genomes i.e., “blue” gene in each circle is ortholog in that genome for “blue” gene in C. trachomatis. Blue, glyA, serine hydroxymethyl-transferase; red, tryptophanyl-tRNA synthetase; yellow, mdhC, malate dehydrogenase; green, V-type ATPase, subunit A; cyan, pdhA, pyruvate dehydrogenase; black, GTP-binding protein lepa; magenta, transcription termination factor rho; brown, yhbG, probable ABC transporter ATP-binding protein; orange, pykF, pyruvate kinase; olive green, conserved hypothetical protein; gray, acetyl-CoA carboxylase beta subunit; pink, threonyl-tRNA synthetase; violet, lysS, lysyl-tRNA synthetase; light green, leuS, leucyl-tRNA synthetase. Those denoted in boldface above were used for C. trachomatis MLST. ompA gene location is shown for C. trachomatis (dark green).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2819883&req=5

Figure 1: Comparison of 14 housekeeping genes among genome sequences of 4 Chlamydiaceae species and 7 strains. Circle 1, genes on forward Chlamydia trachomatis strand, color coded by role category; Circle 2, genes on reverse C. trachomatis strand; Circle 3, multilocus sequence typing (MLST) candidates, C. trachomatis; Circle 4, MLST candidates, C. pneumoniae AR39; Circle 5, MLST candidates, C. caviae (GPIC); Circle 6, MLST candidates, C. muridarum (MoPn). Colors in circles 3, 4, 5 and 6 are consistent for each gene across genomes i.e., “blue” gene in each circle is ortholog in that genome for “blue” gene in C. trachomatis. Blue, glyA, serine hydroxymethyl-transferase; red, tryptophanyl-tRNA synthetase; yellow, mdhC, malate dehydrogenase; green, V-type ATPase, subunit A; cyan, pdhA, pyruvate dehydrogenase; black, GTP-binding protein lepa; magenta, transcription termination factor rho; brown, yhbG, probable ABC transporter ATP-binding protein; orange, pykF, pyruvate kinase; olive green, conserved hypothetical protein; gray, acetyl-CoA carboxylase beta subunit; pink, threonyl-tRNA synthetase; violet, lysS, lysyl-tRNA synthetase; light green, leuS, leucyl-tRNA synthetase. Those denoted in boldface above were used for C. trachomatis MLST. ompA gene location is shown for C. trachomatis (dark green).
Mentions: We genome-sequenced 7 strains from 4 species of the 2 genera of Chlamydiaceae: C. trachomatis (strains D/UW-3/CX [18] and A/Har-13 [19]), Chlamydia muridarum (rodent strain MoPn [20]), Chlamydophila pneumoniae (human strains AR39 [20]; CWL029 [21], and J138 [21]), and Chlamydophila caviae (guinea pig inclusion conjunctivitis strain [22]), the most distantly related species of Chlamydiaceae. On the basis of comparative genomics (20) and comparisons generated by CGView (23), we identified an initial candidate pool of 14 housekeeping genes (Figure 1) present in all 7 genomes with an average BLAST score ratio (BSR) (24) >0.5 for orthologs queried against C. caviae relative to the BLAST score of each sequence against itself. The BSR of >0.5 provides a cutoff to select genes that have lower levels of nucleotide sequence divergence in the genome (i.e., putative housekeeping genes). We then selected 7 genes (Figure 1) on the basis of i) diverse chromosomal regions where a single recombinational exchange would be unlikely to co-introduce >1 selected gene; ii) regions where several contiguous genes were involved in metabolic or key functions; iii) essential metabolic enzymes (e.g., tRNA synthases); iv) genes without similarity to human genes; and v) no genes under diversifying selection.

Bottom Line: Twenty-nine of 52 alleles had nonuniform distributions of frequencies across regions (p<0.001).Recombinant strains were observed among STI clusters.Single nucleotide polymorphisms (SNPs) were predictive of disease specificity.

View Article: PubMed Central - PubMed

Affiliation: Children's Global Health Initiativ, Children's Hospital Oakland Research Institute, Oakland, California 94609, USA. ddean@chori.org

ABSTRACT
Chlamydia trachomatis is a global cause of blinding trachoma and sexually transmitted infections (STIs). We used comparative genomics of the family Chlamydiaceae to select conserved housekeeping genes for C. trachomatis multilocus sequencing, characterizing 19 reference and 68 clinical isolates from 6 continental/subcontinental regions. There were 44 sequence types (ST). Identical STs for STI isolates were recovered from different regions, whereas STs for trachoma isolates were restricted by continent. Twenty-nine of 52 alleles had nonuniform distributions of frequencies across regions (p<0.001). Phylogenetic analysis showed 3 disease clusters: invasive lymphogranuloma venereum strains, globally prevalent noninvasive STI strains (ompA genotypes D/Da, E, and F), and nonprevalent STI strains with a trachoma subcluster. Recombinant strains were observed among STI clusters. Single nucleotide polymorphisms (SNPs) were predictive of disease specificity. Multilocus and SNP typing can now be used to detect diverse and emerging C. trachomatis strains for epidemiologic and evolutionary studies of trachoma and STI populations worldwide.

Show MeSH
Related in: MedlinePlus