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

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 additionall...

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Bibliographic Details
Published in:BMC microbiology 2020-04, Vol.20 (1), p.81-9, Article 81
Main Authors: Kwan, Philip Kam Weng, Lin, Wenwei, Naim, Ahmad Nazri Mohamed, Periaswamy, Balamurugan, De Sessions, Paola Florez, Hibberd, Martin L, Paton, Nicholas I
Format: Article
Language:English
Subjects:
Amoxicillin
Anti-tuberculosis drugs
Antitubercular agents
Antitubercular Agents - pharmacology
Assaying
Bacterial Proteins - genetics
Bactericidal activity
Biosynthesis
Blood
Blood - microbiology
Blood tests
Clavulanic acid
Drug Combinations
Drug development
Drug Repositioning
Drugs
Ethambutol
Ethambutol - pharmacology
Fatty acids
Gene expression
Gene Expression Profiling - methods
Gene Expression Regulation, Bacterial - drug effects
Genes
Humans
Isoniazid
Isoniazid - pharmacology
Mechanism of action
Models, Biological
Moxifloxacin
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - growth & development
Oligonucleotide Array Sequence Analysis
Pyrazinamide
Pyrazinamide - pharmacology
Rifampin
Rifampin - pharmacology
Sputum
Sputum - microbiology
Studies
Transcription
Transcriptome
Tuberculosis
Whole blood assay
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Summary: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. 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 
ISSN:1471-2180
1471-2180
DOI:10.1186/s12866-020-01766-y