Please use this identifier to cite or link to this item: https://doi.org/10.1186/s12866-020-01766-y
Title: Gene expression responses to anti-tuberculous drugs in a whole blood model
Authors: Kwan, P.K.W. 
Lin, W. 
Naim, A.N.M.
Periaswamy, B.
De Sessions, P.F.
Hibberd, M.L. 
Paton, N.I. 
Keywords: Anti-tuberculosis drugs
Faropenem
Gene expression
Mechanism of action
Microarray
Transcriptome
Tuberculosis
Whole blood assay
Issue Date: 2020
Publisher: BioMed Central Ltd.
Citation: Kwan, P.K.W., Lin, W., Naim, A.N.M., Periaswamy, B., De Sessions, P.F., Hibberd, M.L., Paton, N.I. (2020). Gene expression responses to anti-tuberculous drugs in a whole blood model. BMC Microbiology 20 (1) : 81. ScholarBank@NUS Repository. https://doi.org/10.1186/s12866-020-01766-y
Rights: Attribution 4.0 International
Abstract: 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. © 2020 The Author(s).
Source Title: BMC Microbiology
URI: https://scholarbank.nus.edu.sg/handle/10635/199214
ISSN: 1471-2180
DOI: 10.1186/s12866-020-01766-y
Rights: Attribution 4.0 International
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1186_s12866_020_01766_y.pdf1.22 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

1
checked on Nov 20, 2021

Page view(s)

23
checked on Nov 18, 2021

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons