biomedical and healthCAre Data Discovery Index Ecosystem
biomedical and healthCAre Data Discovery Index Ecosystem
| Title: | Mutation of the RNA polymerase β-subunit gene promotes hetero-to-homo conversion of ß-lactam resistance of methicillin-resistant Staphylococcus aureus
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| dateReleased: |
08-27-2013
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| description: |
Three types of phenotypic expression of ß-lactam resistance has been reported in MRSA: heterogeneous-, homogeneous-, and Eagle-type resistance. Heterogeneous to homogeneous (hetero-to-homo) conversion of ß-lactam resistance is postulated to be caused by a chromosomal mutation (chr*) together with mecA-gene expression. The Eagle-type resistance is a special pattern of chr* expression in the pre-MRSA strain N315 under the strong mecI-gene mediated repression of mecA gene transcription. Here, for the identification of chr*, experiments were conducted using an in-vitro derived homogeneously imipenem-resistant MRSA strain N315∆IPH5 (∆IPH5). The strain was selected with imipenem 8 mg/L from the heterogeneously imipenem-resistant MRSA strain N315∆IP (∆IP). The whole genome sequencing of ∆IPH5 revealed the presence of a unique mutation in the rpoB gene, rpoB(N967I), causing the amino-acid (AA) substitution of Asp by Ile at the 967th AA position of the RNA polymerase ß subunit. The effect of the mutation on the phenotypic change was confirmed by constructing and studying the phenotype of the strains H5rpoB(I967N), a ∆IPH5-derived strain cured of the rpoB mutation, and N315rpoB(N967I), a N315-derived strain introduced with the mutated rpoB gene. H5rpoB(I967N) regained the hetero-MRSA phenotype, and the mutant strain N315rpoB(N967I) showed an Eagle-type phenotype similar to that of N315h4. Furthermore, subsequent whole genome sequencing revealed that N315h4 also had a missense mutation in the rpoB gene rpoB(R644H). The rpoB mutations caused decreased autolysis, prolonged doubling-time, and tolerance to bactericidal concentrations of methicillin. We concluded that the certain rpoB mutations are chr* responsible for the hetero-to-homo phenotypic conversion of MRSA. We compared the gene expression profiles of the wild-type strain and rpoB mutant (N967I) using a 60mer oligo array.
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| privacy: |
not applicable
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| aggregation: |
instance of dataset
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| ID: |
E-GEOD-42218
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| refinement: |
raw
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| alternateIdentifiers: |
42218
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| keywords: |
functional genomics
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| dateModified: |
05-03-2014
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| availability: |
available
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| types: |
gene expression
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| name: |
Staphylococcus aureus
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| ID: |
A-GEOD-16176
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| name: |
NimbleGen Staphylococcus aureus 3.8K oligo array [2009_08_03_RDKK206_Saur_60mer_expr]
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| accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-42218/E-GEOD-42218.raw.1.zip |
| storedIn: |
ArrayExpress
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| qualifier: |
gzip compressed
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| format: |
TXT
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| accessType: |
download
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| authentication: |
none
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| authorization: |
none
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| accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-42218/E-GEOD-42218.processed.1.zip |
| storedIn: |
ArrayExpress
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| qualifier: |
gzip compressed
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| format: |
TXT
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| accessType: |
download
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| authentication: |
none
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| authorization: |
none
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| accessURL: | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42218 |
| storedIn: |
Gene Expression Omnibus
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| qualifier: |
not compressed
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| format: |
HTML
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| accessType: |
landing page
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| primary: |
true
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| authentication: |
none
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| authorization: |
none
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| abbreviation: |
EBI
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| homePage: | http://www.ebi.ac.uk/ |
| ID: |
SCR:004727
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| name: |
European Bioinformatics Institute
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| homePage: | https://www.ebi.ac.uk/arrayexpress/ |
| ID: |
SCR:002964
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| name: |
ArrayExpress
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