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Evaluation of the efficacy of valproic acid and suberoylanilide hydroxamic acid (vorinostat) in enhancing the effects of first-line tuberculosis drugs against intracellular Mycobacterium tuberculosis.
- Source :
-
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases [Int J Infect Dis] 2018 Apr; Vol. 69, pp. 78-84. Date of Electronic Publication: 2018 Mar 02. - Publication Year :
- 2018
-
Abstract
- Background: New tuberculosis (TB) drug treatment regimens are urgently needed. This study evaluated the potential of the histone deacetylase inhibitors (HDIs) valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) to enhance the effects of first-line anti-TB drugs against intracellular Mycobacterium tuberculosis.<br />Methods: M. tuberculosis H37Rv cultures were exposed to VPA or SAHA over 6 days, in the presence or absence of isoniazid (INH) and rifampicin (RIF). The efficacy of VPA and SAHA against intracellular M. tuberculosis with and without INH or RIF was tested by treating infected macrophages. Bactericidal activity was assessed by counting mycobacterial colony-forming units (CFU).<br />Results: VPA treatment exhibited superior bactericidal activity to SAHA (2-log CFU reduction), while both HDIs moderately improved the activity of RIF against extracellular M. tuberculosis. The bactericidal effect of VPA against intracellular M. tuberculosis was greater than that of SAHA (1-log CFU reduction) and equalled that of INH (1.5-log CFU reduction). INH/RIF and VPA/SAHA combination treatment inhibited intracellular M. tuberculosis survival in a shorter time span than monotherapy (3days vs. 6 days).<br />Conclusions: VPA and SAHA have adjunctive potential to World Health Organization-recommended TB treatment regimens. Clinical evaluation of the two drugs with regard to reducing the treatment duration and improving treatment outcomes in TB is warranted.<br /> (Copyright © 2018. Published by Elsevier Ltd.)
- Subjects :
- Histone Deacetylase Inhibitors pharmacology
Humans
Isoniazid pharmacology
Macrophages cytology
Macrophages microbiology
Mycobacterium tuberculosis drug effects
Rifampin pharmacology
THP-1 Cells
Vorinostat
Antitubercular Agents pharmacology
Hydroxamic Acids pharmacology
Tuberculosis drug therapy
Valproic Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3511
- Volume :
- 69
- Database :
- MEDLINE
- Journal :
- International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
- Publication Type :
- Academic Journal
- Accession number :
- 29501835
- Full Text :
- https://doi.org/10.1016/j.ijid.2018.02.021