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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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Related in: MedlinePlus

M. catarrhalis CRISPR direct repeat consensus sequences cluster into two clades. The relationship of the direct repeat (DR) consensus sequences of the 15 identified CRISPR loci were analyzed by the Neighbor-Joining method with distances calculated from the absolute number of differences with proportionally distributed gaps, computed from 1000 boot-strapping replications with random tie-braking.
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Figure 6: M. catarrhalis CRISPR direct repeat consensus sequences cluster into two clades. The relationship of the direct repeat (DR) consensus sequences of the 15 identified CRISPR loci were analyzed by the Neighbor-Joining method with distances calculated from the absolute number of differences with proportionally distributed gaps, computed from 1000 boot-strapping replications with random tie-braking.

Mentions: Clustered regularly interspaced short palindromic repeat (CRISPR) elements serve as a means of bacterial self-defense against bacteriophage and plasmid infection (recently reviewed in [34] and [35]). An average prokaryotic genome contains one CRISPR element comprised of 28 repeat-spacer units. The genome of M. catarrhalis RH4 possesses a greater than average number of CRISPR loci, containing one putative and two known CRISPR elements [13]. We sought to determine if elevated numbers of CRISPR elements are common amongst isolates of M. catarrhalis by analyzing each genome for the number, placement and context of CRISPR loci. Of the twelve strains, only O35E did not contain a CRISPR element. The remaining eleven strains contained an average of 1.4 ± 0.5 CRISPR elements (Table 5). These elements were comprised of direct repeats of 28.1 ± 0.3 nucleotides separated by spacer sequences 32 ± 0.7 bp in length, consistent with previous reports [36,37]. Additional analysis of the direct repeat segments indicated that the direct repeat sequence consensus for each CRISPR element could be split into one of two clades, of which clade 1 contains 80% of the repeat sequences (12/15; Figure 6). While the length of the direct repeat and spacer sequence elements demonstrated only minor variation between strains, the number of spacer sequences varied substantially, ranging between 3 to 48 per element (18.3 ± 11.7 bp). No similarity could be found amongst the spacer consensus sequences between strains, nor does similarity exist between the spacer consensus sequences and a non-M. catarrhalis nucleic acid sequence, presently precluding the identification of the invading nucleic acid(s) these sequences defend against.


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)

M. catarrhalis CRISPR direct repeat consensus sequences cluster into two clades. The relationship of the direct repeat (DR) consensus sequences of the 15 identified CRISPR loci were analyzed by the Neighbor-Joining method with distances calculated from the absolute number of differences with proportionally distributed gaps, computed from 1000 boot-strapping replications with random tie-braking.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: M. catarrhalis CRISPR direct repeat consensus sequences cluster into two clades. The relationship of the direct repeat (DR) consensus sequences of the 15 identified CRISPR loci were analyzed by the Neighbor-Joining method with distances calculated from the absolute number of differences with proportionally distributed gaps, computed from 1000 boot-strapping replications with random tie-braking.
Mentions: Clustered regularly interspaced short palindromic repeat (CRISPR) elements serve as a means of bacterial self-defense against bacteriophage and plasmid infection (recently reviewed in [34] and [35]). An average prokaryotic genome contains one CRISPR element comprised of 28 repeat-spacer units. The genome of M. catarrhalis RH4 possesses a greater than average number of CRISPR loci, containing one putative and two known CRISPR elements [13]. We sought to determine if elevated numbers of CRISPR elements are common amongst isolates of M. catarrhalis by analyzing each genome for the number, placement and context of CRISPR loci. Of the twelve strains, only O35E did not contain a CRISPR element. The remaining eleven strains contained an average of 1.4 ± 0.5 CRISPR elements (Table 5). These elements were comprised of direct repeats of 28.1 ± 0.3 nucleotides separated by spacer sequences 32 ± 0.7 bp in length, consistent with previous reports [36,37]. Additional analysis of the direct repeat segments indicated that the direct repeat sequence consensus for each CRISPR element could be split into one of two clades, of which clade 1 contains 80% of the repeat sequences (12/15; Figure 6). While the length of the direct repeat and spacer sequence elements demonstrated only minor variation between strains, the number of spacer sequences varied substantially, ranging between 3 to 48 per element (18.3 ± 11.7 bp). No similarity could be found amongst the spacer consensus sequences between strains, nor does similarity exist between the spacer consensus sequences and a non-M. catarrhalis nucleic acid sequence, presently precluding the identification of the invading nucleic acid(s) these sequences defend against.

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