Rao M, et al. - The potential of the histone deacetylase inhibitors (HDIs) valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) in enhancing the effects of first-line tuberculosis (TB) drugs against intracellular Mycobacterium tuberculosis (M. tb) was investigated. In this work, VPA treatment showed superior bactericidal activity to SAHA, while both HDIs moderately improved the activity of rifampicin (RIF) against extracellular M. tb. Against intracellular M. tb, the bactericidal effect of VPA was greater than SAHA and equalled that of isoniazid (INH). INH/RIF and VPA/SAHA combination treatment resulted in inhibition of intracellular M. tb survival in a shorter time span than monotherapy. Findings thereby suggest that VPA and SAHA have an adjunctive potential to WHO-recommended TB treatment regimens.