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Journal of Infectious Diseases and Therapy ISSN: 2332-0877 | Volume: 6
Infectious Diseases
4
th
Annual Congress on
Neglected Tropical & Infectious Diseases
5
th
International Conference on
August 29-30, 2018 | Boston, USA
&
Role of FoxO in the regulation of Metformin-stimulated energy stress in
Echinococcus spp
Julia A Loos, Valeria A Dávila
and
Andrea C Cumino
The University of Yaoundé I, Yaoundé, Cameroon
W
e have previously shown that Metformin (Met), an anti-hyperglycemic and anti-proliferative drug, exhibits considerable
in vitro and in vivo activity against
E. granulosus
metacestodes. Here, we extended the study and demonstrated that the
drug also possess chemopreventive properties against alveolar echinococcosis in mice. As drug administration was shown to
induce the Eg-AMPK activation, its anti-echinococcal effects might be a consequence of cellular energy charge depletion in
the parasite. Based on this and the fact that only one FoxO transcription factor is present in the genome of
Echinococcus spp,
the aim of this work is investigate the activation state of FoxO and its relation with the expression of genes encoding sirtuins
and key autophagy-related proteins in parasites incubated under both control and energy-stress conditions. Eg-FoxO sequence
reveals several post-translationally modifiable residues highly conserved. By in totoimmunolocalization assays, we detected the
expression and subcellular localization of a phosphorylated (Ser352) and an acetylated (Lys373) form of Eg-FoxO in control
and Met-treated protoscoleces. Interestingly, similar expression patterns were observed in both samples. Additionally, by qPCR
analysis, we found that Met produced an increase in the transcriptional expression of sirt and/or atg genes in
E. granulosus
protoscoleces and metacestodes and in
E. multilocularis
primary cells. In this regards, BLASTn analysis of the upstream
sequences in putative promoters of several of these genes showed the conserved binding motif described for FoxO-activated
genes. These results suggest a possible role of FoxO in the transcriptional regulation of
Echinococcus spp
. under energy stress
conditions. We also detected expression of Atg8 polypeptide (LC3) with both a diffuse and punctate staining in control and
Met-treated
E. granulosus
protoscoleces and
E. multilocularis
vesicles. However, western blot analysis demonstrated higher
levels of Eg-Atg8-PE (LC3-II) in Met-treated protoscoleces, suggesting a possible induction of autophagy under this condition.
Altogether, our data indicate that FoxO, Sirt and autophagy might participate in the regulation of Met-stimulated energy stress
in
Echinococcus spp
.
Biography
Julia A Loos has a PhD in Biological Science (National University of Mar del Plata, 2017) and she is currently working as a postdoc under the direction of Prof. Dr.
Andrea Cumino. She has been serving as assistant teacher for subjects such as Histology, General Microbiology and Pharmacology that are part of the Biology,
Biochemistry and Medicine courses of study. She participates in several research projects on Parasitology and has published original articles. Currently, her
research is focused on the study of intermediary metabolism and energy control in the larval stage of
Echinococcus spp
.
julialoos@hotmail.com,
acumino@gmail.comJulia A Loos, J Infect Dis Ther 2018, Volume 6
DOI: 10.4172/2332-0877-C3-045