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Mycobacterium avium genotype is associated with the therapeutic response to lung infection.

Kikuchi T, Kobashi Y, Hirano T, Tode N, Santoso A, Tamada T, Fujimura S, Mitsuhashi Y, Honda Y, Nukiwa T, Kaku M, Watanabe A, Ichinose M - Clin. Microbiol. Infect. (2013)

Bottom Line: In phylogenetic analysis using the genotypic distance aggregated from 16-dimensional VNTR data, 59 M. avium isolates were divided into three clusters, which showed a nearly significant association with therapeutic responses (p 0.06).We then subjected the raw 16-dimensional VNTR data directly to principal component analysis, and identified the genetic features that were significantly associated with the therapeutic response (p <0.05).By further analysis of logistic regression with a stepwise variable-selection, we constructed the highest likelihood multivariate model, adjusted for age, to predict a therapeutic response, using VNTR data from only four minisatellite loci.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Japan.

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VNTR profiles of clinical Mycobacterium avium isolates. M. avium genomic DNA was isolated from 59 subjects: subjects 1–30 with M. avium lung disease responsive to clarithromycin-based multidrug regimens, and subjects 31–59 with lung disease refractory to treatment. The minisatellite loci, MATR-1 to -16, were amplified from mycobacterial DNA by PCR. From the size of the PCR product, the number of repeat units in each minisatellite locus was calculated. The numbers of tandem repeat units at 16 minisatellite loci are shown for each M. avium isolate. Boxes of the same colour represent the same number of tandem repeats.
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fig01: VNTR profiles of clinical Mycobacterium avium isolates. M. avium genomic DNA was isolated from 59 subjects: subjects 1–30 with M. avium lung disease responsive to clarithromycin-based multidrug regimens, and subjects 31–59 with lung disease refractory to treatment. The minisatellite loci, MATR-1 to -16, were amplified from mycobacterial DNA by PCR. From the size of the PCR product, the number of repeat units in each minisatellite locus was calculated. The numbers of tandem repeat units at 16 minisatellite loci are shown for each M. avium isolate. Boxes of the same colour represent the same number of tandem repeats.

Mentions: To evaluate the association of mycobacterial genotype with therapeutic response, we obtained the VNTR profiling data of all M. avium isolates, determining the numbers of tandemly repeated motifs at minisatellite loci in the genome (Fig.1). The VNTR profile of M. avium isolated from each subject consists of 16 integer values from 16 minisatellite loci, MATR-1 to -16; subjects 1–30 had responsive M. avium lung disease, while subjects 31–59 had refractory disease. The 16 × 59 seemingly unrelated data points permit further evaluation of the association between mycobacterial genotype and the clinical response to anti-mycobacterial treatment.


Mycobacterium avium genotype is associated with the therapeutic response to lung infection.

Kikuchi T, Kobashi Y, Hirano T, Tode N, Santoso A, Tamada T, Fujimura S, Mitsuhashi Y, Honda Y, Nukiwa T, Kaku M, Watanabe A, Ichinose M - Clin. Microbiol. Infect. (2013)

VNTR profiles of clinical Mycobacterium avium isolates. M. avium genomic DNA was isolated from 59 subjects: subjects 1–30 with M. avium lung disease responsive to clarithromycin-based multidrug regimens, and subjects 31–59 with lung disease refractory to treatment. The minisatellite loci, MATR-1 to -16, were amplified from mycobacterial DNA by PCR. From the size of the PCR product, the number of repeat units in each minisatellite locus was calculated. The numbers of tandem repeat units at 16 minisatellite loci are shown for each M. avium isolate. Boxes of the same colour represent the same number of tandem repeats.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231998&req=5

fig01: VNTR profiles of clinical Mycobacterium avium isolates. M. avium genomic DNA was isolated from 59 subjects: subjects 1–30 with M. avium lung disease responsive to clarithromycin-based multidrug regimens, and subjects 31–59 with lung disease refractory to treatment. The minisatellite loci, MATR-1 to -16, were amplified from mycobacterial DNA by PCR. From the size of the PCR product, the number of repeat units in each minisatellite locus was calculated. The numbers of tandem repeat units at 16 minisatellite loci are shown for each M. avium isolate. Boxes of the same colour represent the same number of tandem repeats.
Mentions: To evaluate the association of mycobacterial genotype with therapeutic response, we obtained the VNTR profiling data of all M. avium isolates, determining the numbers of tandemly repeated motifs at minisatellite loci in the genome (Fig.1). The VNTR profile of M. avium isolated from each subject consists of 16 integer values from 16 minisatellite loci, MATR-1 to -16; subjects 1–30 had responsive M. avium lung disease, while subjects 31–59 had refractory disease. The 16 × 59 seemingly unrelated data points permit further evaluation of the association between mycobacterial genotype and the clinical response to anti-mycobacterial treatment.

Bottom Line: In phylogenetic analysis using the genotypic distance aggregated from 16-dimensional VNTR data, 59 M. avium isolates were divided into three clusters, which showed a nearly significant association with therapeutic responses (p 0.06).We then subjected the raw 16-dimensional VNTR data directly to principal component analysis, and identified the genetic features that were significantly associated with the therapeutic response (p <0.05).By further analysis of logistic regression with a stepwise variable-selection, we constructed the highest likelihood multivariate model, adjusted for age, to predict a therapeutic response, using VNTR data from only four minisatellite loci.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Japan.

Show MeSH
Related in: MedlinePlus