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| 1 | Correlation between rpoB gene mutation in Mycobacterium avium subspecies paratuberculosis and clinical rifabutin and rifampicin resistance for treatment of Crohn’s disease显示文摘AIM: To investigate overlapping regions of the rpoB gene previously involved with rifamycin resistance in M. tuberculosis and seek correlation between rpoB mutations in clinical MAP strains with susceptibility to RIF and RFB. METHODS: We designed a molecular-based PCR method for the evaluation of rifabutin (RFB) and rifampicin (RIF) resistance based on probable determinant regions within the rpoB gene of MAP, including the 81 bp variable site located between nucleotides 1363 and 1443. The minimum inhibitory concentration (MIC) for RIF was also determined against 11 MAP isolates in attempt to seek correlation with rpoB sequences. RESULTS: We determined that MAP strain 18 had an MIC of > 30 mg/L and ≤ 5 mg/L for RIF and RFB respectively, and a significant and novel rpoB mutation C1367T, compared to an MIC of ≤ 1.0 mg/L for both drugs in the wild type MAP. The 30-fold increase in the MIC was a direct result of the rpoB mutation C1367T, which caused an amino acid change Thr456 to Ile456 in the drug’s binding site. In addition, MAP strain 185 contained five silent rpoB mutations and exhibited an MIC comparable to the wild-type. Moreover, our in vitroselected mutation in MAP strain UCF5 resulted in the generation of a new resistant strain (UCF5-RIF16r) that possessed T1442C rpoB mutation and an MIC > 30 mg/L and > 10 mg/L for RIF and RFB respectively. Sequencing of the entire rpoB gene in MAP strains UCF4, 18, and UCF5-RIF16r revealed an rpoB mutation A2284C further downstream of the 81 bp variable region in UCF4, accounting for observed slight increase in MIC. In addition, no other significant mutations were found in strains 18 and UCF-RIF16r. CONCLUSION: The data clearly illustrates that clinical and in vitro-selected MAP mutants with rpoB mutations result in resistance to RIF and RFB, and that a single amino acid change in the beta subunit may have a significant impact on RIF resistance. Unconventional drug susceptibility testing such as our molecular approach will be beneficial for evaluation of antibiotic effectiveness. This molecular approach may also serve as a model for other drugs used for treatment of MAP infections. | Daniel R Beckler Sammer Elwasila George Ghobrial John F Valentine Saleh A Naser | 2008 | World Journal of Gastroenterology2008，14，17： | 2 |
| 2 | Amphireg-ulin exosomes increase cancer cell invasion 显示文摘 | Higginbotham JN Demory Beckler M Gephart JD | 2011 | CurrBiol2011，21，： | 1 |
| 3 | Activa- tion of the insulin-like growth factor-1 receptor induces resistance to epidermal growth factor receptor antago- nism in head and neck squamous carcinoma cells显示文摘 | Jameson MJ Beckler AD Taniguchi LE | 2011 | Mol Cancer Ther2011，10，11： | 1 |
| 4 | Decreased abundance of trefoil factor 1 transcript in the majority Of gastric carcinomas 显示文摘 | Beckler AD Roche JK Harper JC | 2003 | Cancer2003，98，10： | 1 |
| 5 | Proteomic analysis of exosomes from mutant KRAS colon cancer ceils identifies intercellular transfer of mutant KRAS 显示文摘 | Beckler MD Higginbotham JN Franklin JL | 2013 | Mol Cell Proteomics2013，12，： | 1 |
| 6 | Amphiregulin Exosomes Increase Cancer Cell Invasion显示文摘 | James N. Higginbotham Michelle Demory Beckler Jonathan D. Gephart Jeffrey L. Franklin Galina Bogatcheva Gert-Jan Kremers David W. Piston Gregory D. Ayers Russell E. McConnell Matthew J. Tyska Robert J. Coffey | 2011 | Current Biology2011，，9： | 1 |
| 7 | Amphiregulin exosomes increase cancer cell invasion 显示文摘 | Higginbotham JN Demory Beckler M Gephart JD | 2011 | Curr Biol2011，21，9： | 1 |
| 8 | Decreased abundance of trefoil factor 1 transcript in the majority of gastric carcinomas显示文摘 | Beckler AD Roche JK Harper JC | | 0，，10： | 1 |
| 9 | Am-phiregulin exosomes increase cancer cell invasion显示文摘 | Higginbotham JN Demory Beckler M Gephart JD | 2011 | Curr Biol2011，21，9： | 1 |
| 10 | Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS 显示文摘 | DEMORY BECKLER M HIGGINBOTHAM IN FRANKLIN JL | 2013 | Mol Cell Proteomics2013，12，2： | 1 |
| 11 | Structure and sequence divergence of two archaebacterial genes 显示文摘 | Cue D Beckler G S Reeve J N | 1985 | Proc Natl Acad Sci USA1985，82，： | 1 |
| 12 | Structure and organization of the hisA gene of the thermophilic archaebacterium Methanococcus thermolithotrophicus 显示文摘 | Weil C F Beckler G S Reeve J N | 1987 | Journal of Bacteriology1987，169，10： | 1 |
| 13 | Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS显示文摘 | Demory Beckler M Higginbotham JN Franklin JL | | 0，，2： | 1 |
| 14 | Pro- teomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS 显示文摘 | Demory Beckler M Higginbotham JN Franklin JL | 2013 | Mol Cell Pro- teomics2013，12，2： | 1 |
| 15 | Shewanella putre faciens produces an Fe(Ⅲ )-solubilizing organic ligand dur- ing anaerobic respiration on insoluble Fe( Ⅲ ) oxides 显示文摘 | Taillefert M Beckler J S Carey E | 2007 | Journal of Inorganic Biochemistry2007，101，1112： | 1 |
| 16 | Amphiregulin exosomes increase cancer cell invasion显示文摘 | Higginbotham JN Demory Beckler M Gephart JD | 2011 | Curr Biol2011，21，9： | 1 |
| 17 | Pro- teomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS 显示文摘 | Beckler MD Higginbotham JN Franklin JL | 2013 | Mol Cell Proteomics2013，12，2： | 1 |
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