Dados do Trabalho

Título

ANTI-TRYPANOSOMA CRUZI POTENTIAL OF METABOLITES FROM A SEDIMENT BACTERIUM FROM THE BITTER LAGOON IN CHILEAN PATAGONIA

Introdução

<p>Bitter Lagoon is a small, shallow, saline lagoon in Torres del Paine National Park in Chilean Patagonia, that gather a combination of extreme environments including cold water (6ºC), strongly alkaline water (pH 9.4), and high salinity of 77 g/L. The microorganisms present in this extreme environment developed adaptation strategies at the cellular, biochemical, and molecular levels, producing a diverse array of molecules and metabolites that could be studied as potential pharmaceutical prototypes. Affecting 8 million people mainly in the Americas with a single available drug, Chagas disease is a potentially life-threatening neglected tropical disease, caused by the protozoan parasite <em>Trypanosoma cruzi</em>. The development of new therapies is urgent.&nbsp;</p>

Objetivo (s)

<p>To isolate bacteria from sediments of the Bitter Lagoon in Chilean Patagonia and to evaluate the anti-<em>Trypanosoma cruzi </em>potential of organic extracts containing microbial metabolites.</p>

Material e Métodos

<p>Sediments of the Bitter Lagoon were plated in different media and cultivated for 10 days at 23 ºC. The isolated bacteria were identified by MALDI-TOF MS. The metabolites of one bacterium were extracted with ethyl acetate and the organic extract (PLASE 2.0) was incubated with trypomastigote forms of <em>Trypanosoma cruzi </em>(Y strain) for 24h at 37 ºC. The 50% Effective Concentration was performed, and the viability detected by the mitochondrial activity using the colorimetric assay of resazurin.</p>

Resultados e Conclusão

<p>Sediments of the Bitter Lagoon yielded 14 isolates of bacteria, all Gram-negative, with different morphologies. One orange-coloured Gram-negative bacilli isolate (PLASE 2.0) was cultivated in Marine Agar for 7 days at 23 ºC and the metabolites extracted with ethyl acetate. The extract presented a trypanocidal effect, observed by the lack of mitochondrial activity and no motility of the parasites at the maximal tested concentration of 150 µg/mL. The 50% Inhibitory Concentration (IC50) of PLASE 2.0 resulted in a value of 4.5 µg/mL (SD± 2.1) and using thin-layer chromatography, the extract demonstrated different compounds with different retention factors (Rf values). This result reveals&nbsp;a potent trypanocidal effect of PLASE 2.0,&nbsp;which is promising for the search for a new drug against Chagas disease. Further bio-guided fractionation studies will be conducted to isolate the potential active metabolite(s).</p>

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Palavras Chave

Chagas disease; Trypanosoma cruzi; Bioprospecting