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Entomopathogenic bacteria Photorhabdus luminescens as drug source against Leishmania amazonensis

Published online by Cambridge University Press:  21 November 2017

Ana Maria Antonello ,
Thaís Sartori ,
Ana Paula Folmer Correa ,
Adriano Brandelli ,
Ralf Heermann ,
Luiz Carlos Rodrigues Júnior ,
Alessandra Peres ,
Pedro Roosevelt Torres Romão  and
Onilda Santos Da Silva
Ana Maria Antonello
Affiliation:
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal do Rio Grande do Sul, UFRGS, Rua Sarmento Leite 500 – 90050-170, Porto Alegre, RS, Brazil Laboratório de Imunologia Celular e Molecular, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite 245 – 90050-170, Porto Alegre, RS, Brazil
Thaís Sartori
Affiliation:
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal do Rio Grande do Sul, UFRGS, Rua Sarmento Leite 500 – 90050-170, Porto Alegre, RS, Brazil Laboratório de Imunologia Celular e Molecular, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite 245 – 90050-170, Porto Alegre, RS, Brazil
Ana Paula Folmer Correa
Affiliation:
Departamento de Ciência dos Alimentos, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, Brazil
Adriano Brandelli
Affiliation:
Departamento de Ciência dos Alimentos, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, Brazil
Ralf Heermann
Affiliation:
Biozentrum, Bereich Mikrobiologie, Ludwig-Maximilians-Universität München, Munich, Germany
Luiz Carlos Rodrigues Júnior
Affiliation:
Laboratório de Imunologia Celular e Molecular, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite 245 – 90050-170, Porto Alegre, RS, Brazil
Alessandra Peres
Affiliation:
Laboratório de Imunologia Celular e Molecular, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite 245 – 90050-170, Porto Alegre, RS, Brazil Programa de Pós-Graduação em Reabilitação, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite 245 – 90050-170, Porto Alegre, RS, Brazil
Pedro Roosevelt Torres Romão*
Affiliation:
Laboratório de Imunologia Celular e Molecular, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite 245 – 90050-170, Porto Alegre, RS, Brazil Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite 245 – 90050-170, Porto Alegre, RS, Brazil Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Rua Sarmento Leite 245 – 90050-170, Porto Alegre, RS, Brazil
Onilda Santos Da Silva*
Affiliation:
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal do Rio Grande do Sul, UFRGS, Rua Sarmento Leite 500 – 90050-170, Porto Alegre, RS, Brazil
*
Author for correspondence: Pedro Roosevelt Torres Romão and Onilda Santos da Silva, E-mail: pedror@ufcspa.edu.br and onilda.silva@ufrgs.br
Author for correspondence: Pedro Roosevelt Torres Romão and Onilda Santos da Silva, E-mail: pedror@ufcspa.edu.br and onilda.silva@ufrgs.br
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Abstract

Leishmaniasis is a widely spread and zoonotic disease with serious problems as low effectiveness of drugs, emergence of parasite resistance and severe adverse reactions. In recent years, considerable attention has been given to secondary metabolites produced by Photorhabdus luminescens, an entomopathogenic bacterium. Here, we assessed the leishmanicidal activity of P. luminescens culture fluids. Initially, promastigotes of Leishmania amazonensis were incubated with cell free conditioned medium of P. luminescens and parasite survival was monitored. Different pre-treatments of the conditioned medium revealed that the leishmanicidal activity is due to a secreted peptide smaller than 3 kDa. The Photorhabdus-derived leishmanicidal toxin (PLT) was enriched from conditioned medium and its effect on mitochondrial membrane potential of promastigotes, was determined. Moreover, the biological activity of PLT against amastigotes was evaluated. PLT inhibited the parasite growth and showed significant leishmanicidal activity against promastigote and amastigotes of L. amazonensis. PLT also caused mitochondrial dysfunction in parasites, but low toxicity to mammalian cell and human erythrocytes. Moreover, the anti-amastigote activity was independent of nitric oxide production. In summary, our results highlight that P. luminescens secretes Leishmania-toxic peptide(s) that are promising novel drugs for therapy against leishmaniasis.

Keywords

Secondary metabolitesleishmaniasisleishmanicidal activitymacrophagesmitochondrial dysfunction
Type
Research Article
Information
Parasitology , Volume 145 , Issue 8 , July 2018 , pp. 1065 - 1074
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Copyright
Copyright © Cambridge University Press 2017 

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