Novel Ehrlichia Strain Infecting Cattle Tick Amblyomma neumanni, Argentina, 2018.

In 2018, we detected a novel Ehrlichia strain infecting Amblyomma neumanni ticks in Argentina. The novel strain is phylogenetically related to the ruminant pathogen E. ruminantium and represents a potential risk for veterinary and public health because A. neumanni ticks parasitize domestic and wild ruminants and bite humans.

Evaluation of proline analogs as trypanocidal agents through the inhibition of a Trypanosoma cruzi proline transporter.

BACKGROUND: Trypanosoma cruzi, the etiological agent of Chagas disease, uses proline as its main carbon source, essential for parasite growth and stage differentiation in epimastigotes and amastigotes. Since proline is involved in many essential biological processes in T. cruzi, its transport and metabolism are interesting drug targets. METHODS: Four synthetic proline analogues (ITP-1B/1C/1D/1G) were evaluated as inhibitors of proline transport mediated through the T. cruzi proline permease TcAAAP069. The trypanocidal activity of the compounds was also assessed. RESULTS: The compounds ITP-1B and ITP-1G inhibited proline transport mediated through TcAAAP069 permease in a dose-dependent manner. The analogues ITP-1B, -1D and -1G had trypanocidal effect on T. cruzi epimastigotes with IC50 values between 30 and 40µM. However, only ITP-1G trypanocidal activity was related with its inhibitory effect on TcAAAP069 proline transporter. Furthermore, this analogue strongly inhibited the parasite stage differentiation from epimastigote to metacyclic trypomastigote. Finally, compounds ITP-1B and ITP-1G were also able to inhibit the transport mediated by other permeases from the same amino acid permeases family, TcAAAP. CONCLUSIONS: It is possible to design synthetic amino acid analogues with trypanocidal activity. The compound ITP-1G is an interesting starting point for new trypanocidal drug design which is also an inhibitor of transport of amino acids and polyamines mediated by permeases from the TcAAAP family, such as proline transporter TcAAAP069 among others. GENERAL SIGNIFICANCE: The Trypanosoma cruzi amino acid transporter family TcAAAP constitutes a multiple and promising therapeutic target for the development of new treatments against Chagas disease.

A putative novel strain of Ehrlichia infecting Amblyomma tigrinum associated with Pampas fox (Lycalopex gymnocercus) in Esteros del Iberá ecoregion, Argentina.

The current work evaluated road-killed Pampas foxes (Lycalopex gymnocercus) and their ticks for the presence of vector-borne agents in the ecoregion Esteros del Iberá in northeastern Argentina. Spleen, lung and blood samples and Amblyomma tigrinum adult ticks collected from the foxes were tested by polymerase chain reaction (PCR) assays targeting bacteria of the genera Ehrlichia, Anaplasma, and Rickettsia. All foxes tested were negative for the three genera, but evidence of Ehrlichia and Rickettsia infection was detected in the ticks. One A. tigrinum (out of 12 tested) was infected by an ehrlichial agent, here named Ehrlichia sp. strain Iberá, related to ehrlichial agents recently detected in platypuses in Tasmania (Ornithorhynchus anatinus) and in voles (Myodes rutilus and Myodes rufocanus) and shrews (Sorex araneus) in the Russian Far East. Regarding Rickettsia, all A. tigrinum ticks (100%) were infected by ´Candidatus Rickettsia andeanae´, a member of the spotted fever group rickettsia of unknown pathogenicity. Further research is necessary to unveil the ecology of Ehrlichia sp. strain Iberá as well as its zoonotic relevance. The species of the genus Ehrlichia are known to be pathogenic to mammals, including humans and domestic animals, thus the presence of this ehrlichial agent in A. tigrinum is a potential risk for veterinary and public health, as the adults of A. tigrinum are common parasites of dogs in rural and peri-urban environments, and humans are also frequently bitten by this tick species.

Targeting L-Proline Uptake as New Strategy for Anti-chagas Drug Development.

L-Proline is an important amino acid for the pathogenic protists belonging to Trypanosoma and Leishmania genera. In Trypanosoma cruzi, the etiological agent of Chagas disease, this amino acid is involved in fundamental biological processes such as ATP production, differentiation of the insect and intracellular stages, the host cell infection and the resistance to a variety of stresses. In this study, we explore the L-Proline uptake as a chemotherapeutic target for T. cruzi. Novel inhibitors have been proposed containing the amino acid with a linker and a variable region able to block the transporter. A series of sixteen 1,2,3-triazolyl-proline derivatives have been prepared for in vitro screening against T. cruzi epimastigotes and proline uptake assays. We successfully obtained inhibitors that interfere with the amino acid internalization, which validated our design targeting the metabolite's transport. The presented structures are one of few examples of amino acid transporter inhibitors. The unprecedent application of this strategy on the development of new chemotherapy against Chagas disease, opens a new horizon on antiparasitic drug development against parasitic diseases and other pathologies.

A minimalistic approach to develop new anti-apicomplexa polyamines analogs.

The development of new chemical entities against the major diseases caused by parasites is highly desired. A library of thirty diamines analogs following a minimalist approach and supported by chemoinformatics tools have been prepared and evaluated against apicomplexan parasites. Different member of the series of N,N'-disubstituted aliphatic diamines shown in vitro activities at submicromolar concentrations and high levels of selectivity against Toxoplasma gondii and in chloroquine-sensitive and resistant-strains of Plasmodium falciparum. In order to demonstrate the importance of the secondary amines, ten N,N,N',N'-tetrasubstituted aliphatic diamines derivatives were synthesized being considerably less active than their disubstituted counterpart. Theoretical studies were performed to establish the electronic factors that govern the activity of the compounds.