دورية أكاديمية
Gene expression responses to anti-tuberculous drugs in a whole blood model.
| العنوان: | Gene expression responses to anti-tuberculous drugs in a whole blood model. |
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| المؤلفون: | Kwan PKW; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore., Lin W; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore., Naim ANM; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore., Periaswamy B; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore., De Sessions PF; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore., Hibberd ML; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.; London School of Hygiene & Tropical Medicine, London, UK.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Paton NI; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore. nick_paton@nuhs.edu.sg.; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore. nick_paton@nuhs.edu.sg.; London School of Hygiene & Tropical Medicine, London, UK. nick_paton@nuhs.edu.sg.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. nick_paton@nuhs.edu.sg. |
| المصدر: | BMC microbiology [BMC Microbiol] 2020 Apr 07; Vol. 20 (1), pp. 81. Date of Electronic Publication: 2020 Apr 07. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 100966981 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2180 (Electronic) Linking ISSN: 14712180 NLM ISO Abbreviation: BMC Microbiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : BioMed Central, [2001- |
| مواضيع طبية MeSH: | Antitubercular Agents/*pharmacology , Bacterial Proteins/*genetics , Blood/*microbiology , Gene Expression Profiling/*methods , Mycobacterium tuberculosis/*growth & development , Sputum/*microbiology, Drug Combinations ; Drug Repositioning ; Ethambutol/pharmacology ; Gene Expression Regulation, Bacterial/drug effects ; Humans ; Isoniazid/pharmacology ; Models, Biological ; Mycobacterium tuberculosis/drug effects ; Oligonucleotide Array Sequence Analysis ; Pyrazinamide/pharmacology ; Rifampin/pharmacology |
| مستخلص: | Background: There is a need for better tools to evaluate new or repurposed TB drugs. The whole blood bactericidal activity (WBA) assay has been advocated for this purpose. We investigated whether transcriptional responses in the WBA assay resemble TB responses in vivo, and whether the approach might additionally reveal mechanisms of action. Results: 1422 of 1798 (79%) of differentially expressed genes in WBA incubated with the standard combination of rifampicin, isoniazid, pyrazinamide and ethambutol were also expressed in sputum (P < 0.0001) obtained from patients taking the same combination of drugs; these comprised well-established treatment-response genes. Gene expression profiles in WBA incubated with the standard drugs individually, or with moxifloxacin or faropenem (with amoxicillin and clavulanic acid) clustered by individual drug exposure. Distinct pathways were detected for individual drugs, although only with isoniazid did these relate to known mechanisms of drug action. Conclusions: Substantial agreement between whole blood cultures and sputum and the ability to differentiate individual drugs suggest that transcriptomics may add value to the whole blood assay for evaluating new TB drugs. |
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| معلومات مُعتمدة: | NMRC/CSA/0050/2013 International National Medical Research Council; NMRC/TCR/011-NUHS/2014 International National Medical Research Council |
| فهرسة مساهمة: | Keywords: Anti-tuberculosis drugs; Faropenem; Gene expression; Mechanism of action; Microarray; Transcriptome; Tuberculosis; Whole blood assay |
| المشرفين على المادة: | 0 (Antitubercular Agents) 0 (Bacterial Proteins) 0 (Drug Combinations) 2KNI5N06TI (Pyrazinamide) 8G167061QZ (Ethambutol) V83O1VOZ8L (Isoniazid) VJT6J7R4TR (Rifampin) |
| تواريخ الأحداث: | Date Created: 20200409 Date Completed: 20210406 Latest Revision: 20210406 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7140558 |
| DOI: | 10.1186/s12866-020-01766-y |
| PMID: | 32264819 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1471-2180 |
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| DOI: | 10.1186/s12866-020-01766-y |