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Gene expression analysis of anti-tuberculous drug responses in a whole blood transcriptome model

ABSTRACT: Gene expression analysis of anti-tuberculous drug responses in a whole blood transcriptome model

PROVIDER: PRJNA598207 | ENA |

REPOSITORIES: ENA

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Gene expression analysis of anti-tuberculous drug responses in a whole blood transcriptome model

Project description: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 response. Microarray analysis was performed on Mycobacterium tuberculosis (Mtb) RNA extracted from whole blood cultures, sputum from TB patients on combination treatment, and drug-free broth cultures

2020-03-23 | GSE142756 | GEO

Gene expression responses to anti-tuberculous drugs in a whole blood model.

Project description:BackgroundThere 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.Results1422 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.ConclusionsSubstantial 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.

| S-EPMC7140558 | biostudies-literature

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