Cargando…

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Loc...

Descripción completa

Detalles Bibliográficos
Autores principales: Firdessa, Rebuma, Good, Liam, Amstalden, Maria Cecilia, Chindera, Kantaraja, Kamaruzzaman, Nor Fadhilah, Schultheis, Martina, Röger, Bianca, Hecht, Nina, Oelschlaeger, Tobias A., Meinel, Lorenz, Lühmann, Tessa, Moll, Heidrun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592236/
https://www.ncbi.nlm.nih.gov/pubmed/26431058
http://dx.doi.org/10.1371/journal.pntd.0004041
_version_ 1782393183956631552
author Firdessa, Rebuma
Good, Liam
Amstalden, Maria Cecilia
Chindera, Kantaraja
Kamaruzzaman, Nor Fadhilah
Schultheis, Martina
Röger, Bianca
Hecht, Nina
Oelschlaeger, Tobias A.
Meinel, Lorenz
Lühmann, Tessa
Moll, Heidrun
author_facet Firdessa, Rebuma
Good, Liam
Amstalden, Maria Cecilia
Chindera, Kantaraja
Kamaruzzaman, Nor Fadhilah
Schultheis, Martina
Röger, Bianca
Hecht, Nina
Oelschlaeger, Tobias A.
Meinel, Lorenz
Lühmann, Tessa
Moll, Heidrun
author_sort Firdessa, Rebuma
collection PubMed
description BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS: Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB’s DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS: Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators.
format Online
Article
Text
id pubmed-4592236
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-45922362015-10-09 Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB) Firdessa, Rebuma Good, Liam Amstalden, Maria Cecilia Chindera, Kantaraja Kamaruzzaman, Nor Fadhilah Schultheis, Martina Röger, Bianca Hecht, Nina Oelschlaeger, Tobias A. Meinel, Lorenz Lühmann, Tessa Moll, Heidrun PLoS Negl Trop Dis Research Article BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS: Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB’s DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS: Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators. Public Library of Science 2015-10-02 /pmc/articles/PMC4592236/ /pubmed/26431058 http://dx.doi.org/10.1371/journal.pntd.0004041 Text en © 2015 Firdessa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Firdessa, Rebuma
Good, Liam
Amstalden, Maria Cecilia
Chindera, Kantaraja
Kamaruzzaman, Nor Fadhilah
Schultheis, Martina
Röger, Bianca
Hecht, Nina
Oelschlaeger, Tobias A.
Meinel, Lorenz
Lühmann, Tessa
Moll, Heidrun
Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)
title Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)
title_full Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)
title_fullStr Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)
title_full_unstemmed Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)
title_short Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)
title_sort pathogen- and host-directed antileishmanial effects mediated by polyhexanide (phmb)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592236/
https://www.ncbi.nlm.nih.gov/pubmed/26431058
http://dx.doi.org/10.1371/journal.pntd.0004041
work_keys_str_mv AT firdessarebuma pathogenandhostdirectedantileishmanialeffectsmediatedbypolyhexanidephmb
AT goodliam pathogenandhostdirectedantileishmanialeffectsmediatedbypolyhexanidephmb
AT amstaldenmariacecilia pathogenandhostdirectedantileishmanialeffectsmediatedbypolyhexanidephmb
AT chinderakantaraja pathogenandhostdirectedantileishmanialeffectsmediatedbypolyhexanidephmb
AT kamaruzzamannorfadhilah pathogenandhostdirectedantileishmanialeffectsmediatedbypolyhexanidephmb
AT schultheismartina pathogenandhostdirectedantileishmanialeffectsmediatedbypolyhexanidephmb
AT rogerbianca pathogenandhostdirectedantileishmanialeffectsmediatedbypolyhexanidephmb
AT hechtnina pathogenandhostdirectedantileishmanialeffectsmediatedbypolyhexanidephmb
AT oelschlaegertobiasa pathogenandhostdirectedantileishmanialeffectsmediatedbypolyhexanidephmb
AT meinellorenz pathogenandhostdirectedantileishmanialeffectsmediatedbypolyhexanidephmb
AT luhmanntessa pathogenandhostdirectedantileishmanialeffectsmediatedbypolyhexanidephmb
AT mollheidrun pathogenandhostdirectedantileishmanialeffectsmediatedbypolyhexanidephmb