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Comparative analysis and supragenome modeling of twelve Moraxella catarrhalis clinical isolates.

Davie JJ, Earl J, de Vries SP, Ahmed A, Hu FZ, Bootsma HJ, Stol K, Hermans PW, Wadowsky RM, Ehrlich GD, Hays JP, Campagnari AA - BMC Genomics (2011)

Bottom Line: These findings are consistent with the distributed genome hypothesis (DGH), which posits that the species genome possesses a far greater number of genes than any single isolate.Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement.M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology and Immunology, University at Buffalo, Buffalo, New York, USA.

ABSTRACT

Background: M. catarrhalis is a gram-negative, gamma-proteobacterium and an opportunistic human pathogen associated with otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD). With direct and indirect costs for treating these conditions annually exceeding $33 billion in the United States alone, and nearly ubiquitous resistance to beta-lactam antibiotics among M. catarrhalis clinical isolates, a greater understanding of this pathogen's genome and its variability among isolates is needed.

Results: The genomic sequences of ten geographically and phenotypically diverse clinical isolates of M. catarrhalis were determined and analyzed together with two publicly available genomes. These twelve genomes were subjected to detailed comparative and predictive analyses aimed at characterizing the supragenome and understanding the metabolic and pathogenic potential of this species. A total of 2383 gene clusters were identified, of which 1755 are core with the remaining 628 clusters unevenly distributed among the twelve isolates. These findings are consistent with the distributed genome hypothesis (DGH), which posits that the species genome possesses a far greater number of genes than any single isolate. Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement.

Conclusions: M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity. These findings are in stark contrast with the reported heterogeneity of the species as a whole, as wells as to other bacterial pathogens mediating OM and COPD, providing important insight into M. catarrhalis pathogenesis that will aid in the development of novel therapeutic regimens.

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Comparison of GC3 s plotted against Nc. Representative sequences from each cluster present in the core (blue triangles) and distributed genomes (green squares) were graphed following the of removal of clusters whose sequences were incompatible with the analysis as described in the Methods.
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Figure 5: Comparison of GC3 s plotted against Nc. Representative sequences from each cluster present in the core (blue triangles) and distributed genomes (green squares) were graphed following the of removal of clusters whose sequences were incompatible with the analysis as described in the Methods.

Mentions: Genes stably maintained within a species tend to exhibit similar codon usage, whereas recently acquired genes often use less frequent or rarely utilized codons (reviewed in [28]). This difference in codon usage may result from selective pressure towards optimal translational efficiency in each organism, shaped by differences in the iso-accepting tRNA pools available to the donor and recipient bacterial species [29-31]. To this end, a comprehensive analysis of codon usage was undertaken. The total codon usage of the supragenome demonstrates that leucine and cysteine are the most and least encoded amino acids, respectively, while five amino acids (Asn, Lys, Val, Ala, and Gly) demonstrated minor alterations in usage within proteins encoded by the core and distributed genomes (data not shown). A plot of GC usage in the synonymously variable third position (GC3s) against the effective number of codons (Nc) encoded for in each gene present in the core and distributed genome subsets identified a spherical distribution approximately centered at 35% GC3 s for the core genes, whereas the distributed genes were more diffuse, with no central location (Figure 5). These data highlight a preference in the core genome for codons with adenosine or thymidine in the synonymously variable third position, as >80% of core sequences have a GC3 s between 30 and 45%. Conversely, no such bias appears among the distributed genome.


Comparative analysis and supragenome modeling of twelve Moraxella catarrhalis clinical isolates.

Davie JJ, Earl J, de Vries SP, Ahmed A, Hu FZ, Bootsma HJ, Stol K, Hermans PW, Wadowsky RM, Ehrlich GD, Hays JP, Campagnari AA - BMC Genomics (2011)

Comparison of GC3 s plotted against Nc. Representative sequences from each cluster present in the core (blue triangles) and distributed genomes (green squares) were graphed following the of removal of clusters whose sequences were incompatible with the analysis as described in the Methods.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3045334&req=5

Figure 5: Comparison of GC3 s plotted against Nc. Representative sequences from each cluster present in the core (blue triangles) and distributed genomes (green squares) were graphed following the of removal of clusters whose sequences were incompatible with the analysis as described in the Methods.
Mentions: Genes stably maintained within a species tend to exhibit similar codon usage, whereas recently acquired genes often use less frequent or rarely utilized codons (reviewed in [28]). This difference in codon usage may result from selective pressure towards optimal translational efficiency in each organism, shaped by differences in the iso-accepting tRNA pools available to the donor and recipient bacterial species [29-31]. To this end, a comprehensive analysis of codon usage was undertaken. The total codon usage of the supragenome demonstrates that leucine and cysteine are the most and least encoded amino acids, respectively, while five amino acids (Asn, Lys, Val, Ala, and Gly) demonstrated minor alterations in usage within proteins encoded by the core and distributed genomes (data not shown). A plot of GC usage in the synonymously variable third position (GC3s) against the effective number of codons (Nc) encoded for in each gene present in the core and distributed genome subsets identified a spherical distribution approximately centered at 35% GC3 s for the core genes, whereas the distributed genes were more diffuse, with no central location (Figure 5). These data highlight a preference in the core genome for codons with adenosine or thymidine in the synonymously variable third position, as >80% of core sequences have a GC3 s between 30 and 45%. Conversely, no such bias appears among the distributed genome.

Bottom Line: These findings are consistent with the distributed genome hypothesis (DGH), which posits that the species genome possesses a far greater number of genes than any single isolate.Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement.M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology and Immunology, University at Buffalo, Buffalo, New York, USA.

ABSTRACT

Background: M. catarrhalis is a gram-negative, gamma-proteobacterium and an opportunistic human pathogen associated with otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD). With direct and indirect costs for treating these conditions annually exceeding $33 billion in the United States alone, and nearly ubiquitous resistance to beta-lactam antibiotics among M. catarrhalis clinical isolates, a greater understanding of this pathogen's genome and its variability among isolates is needed.

Results: The genomic sequences of ten geographically and phenotypically diverse clinical isolates of M. catarrhalis were determined and analyzed together with two publicly available genomes. These twelve genomes were subjected to detailed comparative and predictive analyses aimed at characterizing the supragenome and understanding the metabolic and pathogenic potential of this species. A total of 2383 gene clusters were identified, of which 1755 are core with the remaining 628 clusters unevenly distributed among the twelve isolates. These findings are consistent with the distributed genome hypothesis (DGH), which posits that the species genome possesses a far greater number of genes than any single isolate. Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement.

Conclusions: M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity. These findings are in stark contrast with the reported heterogeneity of the species as a whole, as wells as to other bacterial pathogens mediating OM and COPD, providing important insight into M. catarrhalis pathogenesis that will aid in the development of novel therapeutic regimens.

Show MeSH
Related in: MedlinePlus