Details

Autor(en) / Beteiligte

• Lagunas-Rangel, Francisco Alejandro
• Bazán-Tejeda, María Luisa
• García-Villa, Enrique
• Bermúdez-Cruz, Rosa María

Titel

Nicotinamide induces G2 cell cycle arrest in Giardia duodenalis trophozoites and promotes changes in sirtuins transcriptional expression

Ist Teil von

• Experimental parasitology, 2020-02, Vol.209 (2508), p.107822-107822, Article 107822

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Giardia duodenalis is a flagellated unicellular eukaryotic microorganism that commonly causes diarrheal disease throughout the world. Treatment of giardiasis is limited to nitroheterocyclic compounds as metronidazole and benzimidazoles as albendazole, where remarkably treatment failure is relatively common. Consequently, the need for new options to treat this disease is underscored. We predicted by a bioinformatic approach that nicotinamide inhibits Giardia sirtuins by the nicotinamide exchange pathway, and since sirtuins are involved in cell cycle control, they could be related with arrest and decrease of viability. When trophozoites were treated with nicotinamide (NAM), a strong arrest of Giardia trophozoites in G2 phase was observed and at the same time changes in transcriptional expression of sirtuins were produced. Interestingly, the G2 arrest is not related to double-strand breaks, which strengthens the role of sirtuins in the control of the Giardia cell cycle. Results with NAM-treated trophozoites as predicted demonstrate antigiardial effects and thus open new options for the treatment of giardiasis, either with the combination of nicotinamide with another antigiardial drug, or with the design of specific inhibitors for Giardia sirtuins. [Display omitted] •Nicotinamide induces a strong G2 arrest in Giardia trophozoites and decreases viability alone or in combination with MTZ.•We predicted that NAM inhibits Giardia sirtuins through the nicotinamide exchange pathway.•NAM promotes changes in the transcriptional expression of Giardia sirtuins.•These findings open new options for the treatment of giardiasis.