Comparative analysis and supragenome modeling of twelve Moraxella catarrhalis clinical isolates View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-01-26

AUTHORS

Jeremiah J Davie, Josh Earl, Stefan PW de Vries, Azad Ahmed, Fen Z Hu, Hester J Bootsma, Kim Stol, Peter WM Hermans, Robert M Wadowsky, Garth D Ehrlich, John P Hays, Anthony A Campagnari

ABSTRACT

BackgroundM. 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.ResultsThe 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.ConclusionsM. 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. More... »

PAGES

70

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2164-12-70

DOI

http://dx.doi.org/10.1186/1471-2164-12-70

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1036426417

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21269504


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25 schema:description BackgroundM. 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.ResultsThe 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.ConclusionsM. 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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31 schema:keywords M. catarrhalis
32 M. catarrhalis clinical isolates
33 M. catarrhalis pathogenesis
34 Moraxella catarrhalis
35 Organization data
36 United States
37 analysis
38 antibiotics
39 available genomes
40 bacterial pathogens
41 beta-lactam antibiotics
42 catarrhalis
43 chronic obstructive pulmonary disease
44 clinical isolates
45 clusters
46 comparative analysis
47 conditions
48 content
49 contrast
50 cost
51 data
52 development
53 disease
54 distributed genome hypothesis
55 diversity
56 exacerbation
57 findings
58 gene cluster
59 gene content
60 genes
61 genic diversity
62 genome
63 genome hypothesis
64 genomic sequences
65 greater number
66 greater understanding
67 heterogeneity
68 highlights
69 human pathogens
70 hypothesis
71 important insights
72 indirect costs
73 insights
74 isolates
75 medium
76 modeling
77 novel therapeutic regimens
78 number
79 obstructive pulmonary disease
80 opportunistic human pathogen
81 otitis media
82 pathogen genomes
83 pathogenesis
84 pathogenic potential
85 pathogens
86 potential
87 predictive analysis
88 pulmonary disease
89 regimens
90 resistance
91 sequence
92 single isolate
93 species
94 species genomes
95 stark contrast
96 state
97 supragenome
98 therapeutic regimens
99 total
100 ubiquitous resistance
101 understanding
102 variability
103 wells
104 whole
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