Mitochondrial dysfunction in Trypanosoma cruzi: the role of Serratia marcescens prodigiosin in the alternative treatment of Chagas disease

Abstract

BackgroundChagas disease is a health threat for many people, mostly those living in Latin America. One of the most important problems in treatment is the limitation of existing drugs. Prodigiosin, produced by Serratia marcescens (Rhodnius prolixus endosymbiont), belongs to the red-pigmented bacterial prodiginine family, which displays numerous biological activities, including antibacterial, antifungal, antiprotozoal, antimalarial, immunosuppressive, and anticancer properties. Here we describe its effects on Trypanosoma cruzi mitochondria belonging to Tc I and Tc II.ResultsParasites exposed to prodigiosin altered the mitochondrial function and oxidative phosphorylation could not have a normal course, probably by inhibition of complex III. Prodigiosin did not produce cytotoxic effects in lymphocytes and Vero cells and has better effects than benznidazole. Our data suggest that the action of prodigiosin on the parasites is mediated by mitochondrial structural and functional disruptions that could lead the parasites to an apoptotic-like cell death process.ConclusionsHere, we propose a potentially useful trypanocidal agent derived from knowledge of an important aspect of the natural life cycle of the parasite: the vector-parasite interaction. Our results indicate that prodigiosin could be a good candidate for the treatment of Chagas disease.

Genome sequencing and assessment of plant growth-promoting properties of a Serratia marcescens strain isolated from vermicompost

“…the pig operon), the notorious red pigment, which is widely-conserved across several Serratia isolates [ 38 ]. Prodigiosin is most commonly found in environmental S. marcescens isolates and has been proposed to suppress growth of various fungi [ 47 ], bacteria [ 97 ], protozoans [ 98 ] and even viruses [ 99 ]. It has been recently suggested that prodigiosin has affinity for the lipid bilayer of the plasma membrane, causing outer membrane damage [ 100 ].…”

Characterization of the microbiota in the guts of Triatoma brasiliensis and Triatoma pseudomaculata infected by Trypanosoma cruzi in natural conditions using culture independent methods

“…The facultative anaerobe S. marcescens biotype A1 isolated from the gut of R. prolixus has been reported to have trypanolitic activity, especially on the Y strain [ 85 ]. Prodigiosin, a pigment in some strains of these bacteria, has been proposed to be responsible for trypanocidal activity [ 85 , 86 ]. However, Castro et al [ 87 , 88 ] proposed that mannose sensitive fimbriae might be directly involved in the trypanocidal activity by connecting bacteria to the surface of the parasite and promoting their adhesion to the protozoan cellular membrane.…”

Invertebrates Mitochondrial Function and Energetic Challenges

“…An interesting example is the study about the control of Chagas disease, which severely affects the health of the human population in Latin America and which is caused by the protozoan parasite Trypanosoma cruzi. Genes et al (2011) reported such bacteria species as Serratia marcescens biotype A1a, which is regularly found in the gut of the vector insect Rhodnius prolixus, and which demonstrates the trypanolytic activity conferred by prodigiosin. Prodigiosin is a potent bacterial tripyrrolic compound with various biological activities.…”