Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival.
Protozoan parasites, such as Leishmania, still pose an enormous public health problem in many countries throughout the world. Current measures are outdated and have some associated drug resistance, prompting the search into novel therapies. Several innovative approaches are under investigation, incl...
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ftdoajarticles:oai:doaj.org/article:3adc307bd3a247b38435df30043617b3 2023-05-15T15:14:23+02:00 Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. Miriam A Lynn Jason Kindrachuk Alexandra K Marr Håvard Jenssen Nelly Panté Melissa R Elliott Scott Napper Robert E Hancock W Robert McMaster 2011-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001141 https://doaj.org/article/3adc307bd3a247b38435df30043617b3 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3104953?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001141 https://doaj.org/article/3adc307bd3a247b38435df30043617b3 PLoS Neglected Tropical Diseases, Vol 5, Iss 5, p e1141 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001141 2022-12-31T12:03:29Z Protozoan parasites, such as Leishmania, still pose an enormous public health problem in many countries throughout the world. Current measures are outdated and have some associated drug resistance, prompting the search into novel therapies. Several innovative approaches are under investigation, including the utilization of host defence peptides (HDPs) as emerging anti-parasitic therapies. HDPs are characterised by their small size, amphipathic nature and cationicity, which induce permeabilization of cell membranes, whilst modulating the immune response of the host. Recently, members of the cathelicidin family of HDPs have demonstrated significant antimicrobial activities against various parasites including Leishmania. The cathelicidin bovine myeloid antimicrobial peptide 28 (BMAP-28) has broad antimicrobial activities and confers protection in animal models of bacterial infection or sepsis. We tested the effectiveness of the use of BMAP-28 and two of its isomers the D-amino acid form (D-BMAP-28) and the retro-inverso form (RI-BMAP-28), as anti-leishmanial agents against the promastigote and amastigote intracellular Leishmania major lifecycle stages.An MTS viability assay was utilized to show the potent antiparasitic activity of BMAP-28 and its protease resistant isomers against L. major promastigotes in vitro. Cell membrane permeability assays, caspase 3/7, Tunel assays and morphologic studies suggested that this was a late stage apoptotic cell death with early osmotic cell lysis caused by the antimicrobial peptides. Furthermore, BMAP-28 and its isomers demonstrated anti-leishmanial activities against intracellular amastigotes within a macrophage infection model.Interestingly, D-BMAP-28 appears to be the most potent antiparasitic of the three isomers against wild type L. major promastigotes and amastigotes. These exciting results suggest that BMAP-28 and its protease resistant isomers have significant therapeutic potential as novel anti-leishmanials. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 5 e1141 |
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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 Miriam A Lynn Jason Kindrachuk Alexandra K Marr Håvard Jenssen Nelly Panté Melissa R Elliott Scott Napper Robert E Hancock W Robert McMaster Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Protozoan parasites, such as Leishmania, still pose an enormous public health problem in many countries throughout the world. Current measures are outdated and have some associated drug resistance, prompting the search into novel therapies. Several innovative approaches are under investigation, including the utilization of host defence peptides (HDPs) as emerging anti-parasitic therapies. HDPs are characterised by their small size, amphipathic nature and cationicity, which induce permeabilization of cell membranes, whilst modulating the immune response of the host. Recently, members of the cathelicidin family of HDPs have demonstrated significant antimicrobial activities against various parasites including Leishmania. The cathelicidin bovine myeloid antimicrobial peptide 28 (BMAP-28) has broad antimicrobial activities and confers protection in animal models of bacterial infection or sepsis. We tested the effectiveness of the use of BMAP-28 and two of its isomers the D-amino acid form (D-BMAP-28) and the retro-inverso form (RI-BMAP-28), as anti-leishmanial agents against the promastigote and amastigote intracellular Leishmania major lifecycle stages.An MTS viability assay was utilized to show the potent antiparasitic activity of BMAP-28 and its protease resistant isomers against L. major promastigotes in vitro. Cell membrane permeability assays, caspase 3/7, Tunel assays and morphologic studies suggested that this was a late stage apoptotic cell death with early osmotic cell lysis caused by the antimicrobial peptides. Furthermore, BMAP-28 and its isomers demonstrated anti-leishmanial activities against intracellular amastigotes within a macrophage infection model.Interestingly, D-BMAP-28 appears to be the most potent antiparasitic of the three isomers against wild type L. major promastigotes and amastigotes. These exciting results suggest that BMAP-28 and its protease resistant isomers have significant therapeutic potential as novel anti-leishmanials. |
format |
Article in Journal/Newspaper |
author |
Miriam A Lynn Jason Kindrachuk Alexandra K Marr Håvard Jenssen Nelly Panté Melissa R Elliott Scott Napper Robert E Hancock W Robert McMaster |
author_facet |
Miriam A Lynn Jason Kindrachuk Alexandra K Marr Håvard Jenssen Nelly Panté Melissa R Elliott Scott Napper Robert E Hancock W Robert McMaster |
author_sort |
Miriam A Lynn |
title |
Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. |
title_short |
Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. |
title_full |
Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. |
title_fullStr |
Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. |
title_full_unstemmed |
Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. |
title_sort |
effect of bmap-28 antimicrobial peptides on leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001141 https://doaj.org/article/3adc307bd3a247b38435df30043617b3 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 5, p e1141 (2011) |
op_relation |
http://europepmc.org/articles/PMC3104953?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001141 https://doaj.org/article/3adc307bd3a247b38435df30043617b3 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001141 |
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PLoS Neglected Tropical Diseases |
container_volume |
5 |
container_issue |
5 |
container_start_page |
e1141 |
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