Gene expression analysis of anti-tuberculous drug responses in a whole blood transcriptome 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 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 Microarray analysis was performed on Mtb RNA taken from whole blood cultures from 4 volunteers, 9 sputum of TB patients on standard combination treatment, and 5 drug-free broth cultures. Mtb (H37Rv strain) was incubated in whole blood cultures for one hour with rifampicin, isoniazid, pyrazinamide, ethambutol individually and in 4-drug combination; with moxifloxacin, faropenem (with amoxicillin and clavulanic acid), and a drug-free control (drugs at Cmax concentrations; each replicate assay prepared from the blood of one of the 4 healthy volunteers).