Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Unsaturated Iso-Type Fatty Acids from the Marine Bacterium Mesoflavibacter zeaxanthinifaciens with Antitrypanosomal Potential

Version 1 : Received: 19 February 2024 / Approved: 21 February 2024 / Online: 22 February 2024 (12:33:09 CET)

A peer-reviewed article of this Preprint also exists.

Santos Ferreira, D.A.; de Castro Levatti, E.V.; Santa Cruz, L.M.; Costa, A.R.; Migotto, Á.E.; Yamada, A.Y.; Camargo, C.H.; Christodoulides, M.; Lago, J.H.G.; Tempone, A.G. Saturated Iso-Type Fatty Acids from the Marine Bacterium Mesoflavibacter zeaxanthinifaciens with Anti-Trypanosomal Potential. Pharmaceuticals 2024, 17, 499. Santos Ferreira, D.A.; de Castro Levatti, E.V.; Santa Cruz, L.M.; Costa, A.R.; Migotto, Á.E.; Yamada, A.Y.; Camargo, C.H.; Christodoulides, M.; Lago, J.H.G.; Tempone, A.G. Saturated Iso-Type Fatty Acids from the Marine Bacterium Mesoflavibacter zeaxanthinifaciens with Anti-Trypanosomal Potential. Pharmaceuticals 2024, 17, 499.

Abstract

Chagas disease is a Neglected Tropical Disease with limited and ineffective therapy. In a search for new antitrypanosomal compounds, we investigated the potential of metabolites from bacteria living in corals and sediments of the Southeastern Brazilian coast. Three corals Tubastraea coccinea, Mussismilia hispida, Madracis decactis and sediments yielded 11 bacterial strains, that were fully identified by MALDI-ToF/MS or gene sequencing, resulting in six genera - Vibrio, Shewanella, Mesoflavibacter, Halomonas, Bacillus and Alteromonas. To conduct this study, EtOAc extracts were prepared and tested against Trypanosoma cruzi. Crude extracts showed IC50 values ranging from 15 to 51 μg/mL against trypomastigotes. The bacterium Mesoflavibacter zeaxanthinifaciens was selected for fractionation, resulting in an active fraction (FII) with IC50 values of 17.7 μg/mL and 23.8 μg/mL against the trypomastigotes and amastigotes, respectively, with neither mammalian cytotoxicity nor hemolytic activity. Using NMR and ESI-HRMS analysis, FII revealed the presence of unsaturated iso-type fatty acids. Its lethal action was investigated, leading to a protein spectral profile of the parasite altered after treatment. FII also induced a rapid permeabilization of the plasma membrane of the parasite, leading to cell death. These findings demonstrate these unsaturated iso-type fatty acids as possible new hits against T. cruzi.

Keywords

marine bacteria; Trypanosoma cruzi; iso-fatty acids; metabolites; antimicrobial

Subject

Biology and Life Sciences, Biology and Biotechnology

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