Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia
Abstract Background Plasmodium falciparum malaria is one of the most widespread parasitic infections in humans and remains a leading global health concern. Malaria elimination efforts are threatened by the emergence and spread of resistance to artemisinin-based combination therapy, the first-line tr...
Published in: | Malaria Journal |
---|---|
Main Authors: | , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
BMC
2017
|
Subjects: | |
Online Access: | https://doi.org/10.1186/s12936-017-2140-1 https://doaj.org/article/e53ac2f55d0b481c96652eb282159804 |
id |
ftdoajarticles:oai:doaj.org/article:e53ac2f55d0b481c96652eb282159804 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:e53ac2f55d0b481c96652eb282159804 2023-05-15T15:13:54+02:00 Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia Ankit Dwivedi Christelle Reynes Axel Kuehn Daniel B. Roche Nimol Khim Maxim Hebrard Sylvain Milanesi Eric Rivals Roger Frutos Didier Menard Choukri Ben Mamoun Jacques Colinge Emmanuel Cornillot 2017-12-01T00:00:00Z https://doi.org/10.1186/s12936-017-2140-1 https://doaj.org/article/e53ac2f55d0b481c96652eb282159804 EN eng BMC http://link.springer.com/article/10.1186/s12936-017-2140-1 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-017-2140-1 1475-2875 https://doaj.org/article/e53ac2f55d0b481c96652eb282159804 Malaria Journal, Vol 16, Iss 1, Pp 1-17 (2017) Plasmodium falciparum Malaria Cambodia Artemisinin resistance k13 Population fragmentation Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2017 ftdoajarticles https://doi.org/10.1186/s12936-017-2140-1 2022-12-31T09:22:46Z Abstract Background Plasmodium falciparum malaria is one of the most widespread parasitic infections in humans and remains a leading global health concern. Malaria elimination efforts are threatened by the emergence and spread of resistance to artemisinin-based combination therapy, the first-line treatment of malaria. Promising molecular markers and pathways associated with artemisinin drug resistance have been identified, but the underlying molecular mechanisms of resistance remains unknown. The genomic data from early period of emergence of artemisinin resistance (2008–2011) was evaluated, with aim to define k13 associated genetic background in Cambodia, the country identified as epicentre of anti-malarial drug resistance, through characterization of 167 parasite isolates using a panel of 21,257 SNPs. Results Eight subpopulations were identified suggesting a process of acquisition of artemisinin resistance consistent with an emergence-selection-diffusion model, supported by the shifting balance theory. Identification of population specific mutations facilitated the characterization of a core set of 57 background genes associated with artemisinin resistance and associated pathways. The analysis indicates that the background of artemisinin resistance was not acquired after drug pressure, rather is the result of fixation followed by selection on the daughter subpopulations derived from the ancestral population. Conclusions Functional analysis of artemisinin resistance subpopulations illustrates the strong interplay between ubiquitination and cell division or differentiation in artemisinin resistant parasites. The relationship of these pathways with the P. falciparum resistant subpopulation and presence of drug resistance markers in addition to k13, highlights the major role of admixed parasite population in the diffusion of artemisinin resistant background. The diffusion of resistant genes in the Cambodian admixed population after selection resulted from mating of gametocytes of sensitive and resistant parasite ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 16 1 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Plasmodium falciparum Malaria Cambodia Artemisinin resistance k13 Population fragmentation Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Plasmodium falciparum Malaria Cambodia Artemisinin resistance k13 Population fragmentation Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Ankit Dwivedi Christelle Reynes Axel Kuehn Daniel B. Roche Nimol Khim Maxim Hebrard Sylvain Milanesi Eric Rivals Roger Frutos Didier Menard Choukri Ben Mamoun Jacques Colinge Emmanuel Cornillot Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia |
topic_facet |
Plasmodium falciparum Malaria Cambodia Artemisinin resistance k13 Population fragmentation Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Plasmodium falciparum malaria is one of the most widespread parasitic infections in humans and remains a leading global health concern. Malaria elimination efforts are threatened by the emergence and spread of resistance to artemisinin-based combination therapy, the first-line treatment of malaria. Promising molecular markers and pathways associated with artemisinin drug resistance have been identified, but the underlying molecular mechanisms of resistance remains unknown. The genomic data from early period of emergence of artemisinin resistance (2008–2011) was evaluated, with aim to define k13 associated genetic background in Cambodia, the country identified as epicentre of anti-malarial drug resistance, through characterization of 167 parasite isolates using a panel of 21,257 SNPs. Results Eight subpopulations were identified suggesting a process of acquisition of artemisinin resistance consistent with an emergence-selection-diffusion model, supported by the shifting balance theory. Identification of population specific mutations facilitated the characterization of a core set of 57 background genes associated with artemisinin resistance and associated pathways. The analysis indicates that the background of artemisinin resistance was not acquired after drug pressure, rather is the result of fixation followed by selection on the daughter subpopulations derived from the ancestral population. Conclusions Functional analysis of artemisinin resistance subpopulations illustrates the strong interplay between ubiquitination and cell division or differentiation in artemisinin resistant parasites. The relationship of these pathways with the P. falciparum resistant subpopulation and presence of drug resistance markers in addition to k13, highlights the major role of admixed parasite population in the diffusion of artemisinin resistant background. The diffusion of resistant genes in the Cambodian admixed population after selection resulted from mating of gametocytes of sensitive and resistant parasite ... |
format |
Article in Journal/Newspaper |
author |
Ankit Dwivedi Christelle Reynes Axel Kuehn Daniel B. Roche Nimol Khim Maxim Hebrard Sylvain Milanesi Eric Rivals Roger Frutos Didier Menard Choukri Ben Mamoun Jacques Colinge Emmanuel Cornillot |
author_facet |
Ankit Dwivedi Christelle Reynes Axel Kuehn Daniel B. Roche Nimol Khim Maxim Hebrard Sylvain Milanesi Eric Rivals Roger Frutos Didier Menard Choukri Ben Mamoun Jacques Colinge Emmanuel Cornillot |
author_sort |
Ankit Dwivedi |
title |
Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia |
title_short |
Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia |
title_full |
Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia |
title_fullStr |
Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia |
title_full_unstemmed |
Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia |
title_sort |
functional analysis of plasmodium falciparum subpopulations associated with artemisinin resistance in cambodia |
publisher |
BMC |
publishDate |
2017 |
url |
https://doi.org/10.1186/s12936-017-2140-1 https://doaj.org/article/e53ac2f55d0b481c96652eb282159804 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 16, Iss 1, Pp 1-17 (2017) |
op_relation |
http://link.springer.com/article/10.1186/s12936-017-2140-1 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-017-2140-1 1475-2875 https://doaj.org/article/e53ac2f55d0b481c96652eb282159804 |
op_doi |
https://doi.org/10.1186/s12936-017-2140-1 |
container_title |
Malaria Journal |
container_volume |
16 |
container_issue |
1 |
_version_ |
1766344410111410176 |