The enemy within: Targeting host-parasite interaction for antileishmanial drug discovery.
The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites' intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2017
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0005480 https://doaj.org/article/6b02853876834728bc8c2635a58c3d34 |
id |
ftdoajarticles:oai:doaj.org/article:6b02853876834728bc8c2635a58c3d34 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:6b02853876834728bc8c2635a58c3d34 2023-05-15T15:04:23+02:00 The enemy within: Targeting host-parasite interaction for antileishmanial drug discovery. Suzanne Lamotte Gerald F Späth Najma Rachidi Eric Prina 2017-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005480 https://doaj.org/article/6b02853876834728bc8c2635a58c3d34 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5464532?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005480 https://doaj.org/article/6b02853876834728bc8c2635a58c3d34 PLoS Neglected Tropical Diseases, Vol 11, Iss 6, p e0005480 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005480 2022-12-31T00:18:51Z The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites' intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host-parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 6 e0005480 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Suzanne Lamotte Gerald F Späth Najma Rachidi Eric Prina The enemy within: Targeting host-parasite interaction for antileishmanial drug discovery. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites' intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host-parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival. |
format |
Article in Journal/Newspaper |
author |
Suzanne Lamotte Gerald F Späth Najma Rachidi Eric Prina |
author_facet |
Suzanne Lamotte Gerald F Späth Najma Rachidi Eric Prina |
author_sort |
Suzanne Lamotte |
title |
The enemy within: Targeting host-parasite interaction for antileishmanial drug discovery. |
title_short |
The enemy within: Targeting host-parasite interaction for antileishmanial drug discovery. |
title_full |
The enemy within: Targeting host-parasite interaction for antileishmanial drug discovery. |
title_fullStr |
The enemy within: Targeting host-parasite interaction for antileishmanial drug discovery. |
title_full_unstemmed |
The enemy within: Targeting host-parasite interaction for antileishmanial drug discovery. |
title_sort |
enemy within: targeting host-parasite interaction for antileishmanial drug discovery. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005480 https://doaj.org/article/6b02853876834728bc8c2635a58c3d34 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 6, p e0005480 (2017) |
op_relation |
http://europepmc.org/articles/PMC5464532?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005480 https://doaj.org/article/6b02853876834728bc8c2635a58c3d34 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005480 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
6 |
container_start_page |
e0005480 |
_version_ |
1766336165310365696 |