International Journal for Parasitology: Drugs and Drug Resistance · Published 2026-08-01 · DOI 10.1016/j.ijpddr.2026.100664
Hae-Ahm Lee, Hye-Jeong Jo, Ji-Youn Hong, Fu-Shi Quan, Eun-Kyung Moon
Naegleria fowleri is a free-living amoeba that causes a rare but almost always fatal brain infection known as primary amoebic meningoencephalitis (PAM). Although amphotericin B (AmB) is considered the primary treatment for PAM, it is often recommended in combination with several other drugs due to side effects associated with high concentrations. In this study, we investigated whether histone deacetylase inhibitors (HDACis) enhance the amoebicidal activity of AmB against N. fowleri. Anti-proliferative and cytotoxic activities were assessed using the cell counting kit and lactate dehydrogenase assays, respectively, and apoptosis induction was evaluated by flow cytometry. Class-specific HDACis, including class I inhibitors MS275 and MGCD0103 and a class II inhibitor MC1568, showed minimal effects on trophozoite viability. In contrast, the pan-HDACis SAHA and JNJ significantly reduced trophozoite viability in a dose- and time-dependent manner. Furthermore, 10 μM SAHA and JNJ significantly reduced the encystation ratio of N. fowleri. Combined treatment with low doses of HDACi (1 μM) and AmB (0.5 μM) produced stronger amoebicidal and pro-apoptotic effects than either agent alone. These combination treatments also exhibited low cytopathic effects on human brain tumor cells. These findings suggest that SAHA and JNJ, particularly in combination with AmB, hold promise as therapeutic candidates against N. fowleri infection while potentially mitigating the severe side effects associated with AmB.
Abstract from DOAJ. Public domain (CC0 1.0).
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Lee, H., Jo, H., Hong, J., et al. (2026). Histone deacetylase inhibitors enhance the amoebicidal activity of amphotericin B against Naegleria fowleri. International Journal for Parasitology: Drugs and Drug Resistance. https://doi.org/10.1016/j.ijpddr.2026.100664