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. Loca...
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ftdoajarticles:oai:doaj.org/article:7b08001768d847378d35e2a6103f602e 2023-05-15T15:09:04+02:00 Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB). Rebuma Firdessa Liam Good Maria Cecilia Amstalden Kantaraja Chindera Nor Fadhilah Kamaruzzaman Martina Schultheis Bianca Röger Nina Hecht Tobias A Oelschlaeger Lorenz Meinel Tessa Lühmann Heidrun Moll 2015-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004041 https://doaj.org/article/7b08001768d847378d35e2a6103f602e EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4592236?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004041 https://doaj.org/article/7b08001768d847378d35e2a6103f602e PLoS Neglected Tropical Diseases, Vol 9, Iss 10, p e0004041 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004041 2022-12-31T12:29:36Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 10 e0004041 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Rebuma Firdessa Liam Good Maria Cecilia Amstalden Kantaraja Chindera Nor Fadhilah Kamaruzzaman Martina Schultheis Bianca Röger Nina Hecht Tobias A Oelschlaeger Lorenz Meinel Tessa Lühmann Heidrun Moll Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB). |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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 |
Article in Journal/Newspaper |
author |
Rebuma Firdessa Liam Good Maria Cecilia Amstalden Kantaraja Chindera Nor Fadhilah Kamaruzzaman Martina Schultheis Bianca Röger Nina Hecht Tobias A Oelschlaeger Lorenz Meinel Tessa Lühmann Heidrun Moll |
author_facet |
Rebuma Firdessa Liam Good Maria Cecilia Amstalden Kantaraja Chindera Nor Fadhilah Kamaruzzaman Martina Schultheis Bianca Röger Nina Hecht Tobias A Oelschlaeger Lorenz Meinel Tessa Lühmann Heidrun Moll |
author_sort |
Rebuma Firdessa |
title |
Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB). |
title_short |
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_sort |
pathogen- and host-directed antileishmanial effects mediated by polyhexanide (phmb). |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0004041 https://doaj.org/article/7b08001768d847378d35e2a6103f602e |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 10, p e0004041 (2015) |
op_relation |
http://europepmc.org/articles/PMC4592236?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004041 https://doaj.org/article/7b08001768d847378d35e2a6103f602e |
op_doi |
https://doi.org/10.1371/journal.pntd.0004041 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
9 |
container_issue |
10 |
container_start_page |
e0004041 |
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1766340293477531648 |