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
Copyright © 2018. Published by Elsevier Ltd..
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.
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).
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).
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:69 |
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| Enthalten in: |
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases - 69(2018) vom: 15. Apr., Seite 78-84 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rao, Martin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.07.2018 Date Revised 02.12.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijid.2018.02.021 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM281589763 |
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| 100 | 1 | |a Rao, Martin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |
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| 500 | |a Date Revised 02.12.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018. Published by Elsevier Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adjunct host-directed therapy | |
| 650 | 4 | |a Histone deacetylase inhibitors | |
| 650 | 4 | |a Mycobacterium tuberculosis | |
| 650 | 4 | |a Repurposed drugs | |
| 650 | 4 | |a Tuberculosis | |
| 650 | 7 | |a Antitubercular Agents |2 NLM | |
| 650 | 7 | |a Histone Deacetylase Inhibitors |2 NLM | |
| 650 | 7 | |a Hydroxamic Acids |2 NLM | |
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| 650 | 7 | |a Valproic Acid |2 NLM | |
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| 700 | 1 | |a Valentini, Davide |e verfasserin |4 aut | |
| 700 | 1 | |a Zumla, Alimuddin |e verfasserin |4 aut | |
| 700 | 1 | |a Maeurer, Markus |e verfasserin |4 aut | |
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