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EuroSciCon Conference on Virology and Infectious Diseases
April 22-23, 2019 | Athens, Greece
Page 39
Archives of Clinical Microbiology
ISSN: 1989-8436
Virology and Infectious Diseases 2019
Wanderley de Souza et al., Arch Clin Microbiol 2019, Volume:10
DOI: 10.4172/1989-8436-C1-016
pathway to ingest molecules required for various metabolic pathways
which are subsequently processed in organelles of the endosome-
lysosome pathways where proteolytic enzymes play a key role. Indeed,
inhibitors of cysteine proteinases are very active in Trypanosoma cruzi;
Trypanosomatids present a contractile vacuole, also localized close to the
flagellar pocket, and that plays a vital role on parasite ionic homeostasis.
Further studies are in progress to identify key molecules involved on this
process; most of the trypanosomatids require mitochondrial activity to
survive. They have only on single and highly ramified mitochondrion.
Compounds that interfere with themitochondrial membrane and/or some
of the key proteins involved in ATP synthesis kill the parasite. Examples
include phospholipid analogues and several inhibitors of the sterol
biosynthesis pathway. We have analyzed several compounds interfering
with these two key metabolic pathways and some of them are able to kill
the parasites at nanomolar concentrations. These compounds are active
against all developmental stages and are, therefore, potential compounds
for further analysis in experimental infected animal models. We will
show some of the first experiments; members of the Trypanosomatidae
family present a special type of peroxisome, known as glycosome, since
most of the glycolytic pathway takes place within this organelle while
in other eukaryotic cells, it takes place in the cytosol. This organelle is
also a potential drug target; they also have a special organelle known
as acidocalcisome, which is vital for the parasite and is involved in the
control of Calcium, which is accumulated as pyrophosphate complexes. It
is also a potential drug target and some compounds have been identified
that interfere with this organelle; another characteristic feature of the
parasite is the presence of a complex array of microtubules localized just
below the plasma membrane (known as sub-pellicular microtubules).
These microtubules are highly stable and have low sensitivity to drugs
such as colchicine, vinblastine, etc. However, they are vital for the
parasite. Due to this fact, we are testing all new compounds that interfere
with microtubule assembly and disassembly