Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline
© 2015 Gaillard et al. Background: Doxycycline is an antibiotic used in combination with quinine or artesunate for malaria treatment or alone for malaria chemoprophylaxis. Recently, one prophylactic failure has been reported, and several studies have highlighted in vitro doxycycline decreased suscep...
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th-mahidol.360752018-11-23T17:36:18Z Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline Tiphaine Gaillard Nathalie Wurtz Sandrine Houzé Kanlaya Sriprawat Chirapat Wangsing Véronique Hubert Jacques Lebras François Nosten Sébastien Briolant Bruno Pradines Institut de recherche biomedicale des armees Unite de Recherche sur les Maladies Infectieuses et Tropicales emergentes HIA Sainte-Anne a Toulon Centre National de Référence du Paludisme Hopital Bichat-Claude-Bernard AP-HP IRD Institut de Recherche pour le Developpement Universite Paris Descartes Mahidol University University of Oxford Institut Pasteur de la Guyane Immunology and Microbiology Medicine © 2015 Gaillard et al. Background: Doxycycline is an antibiotic used in combination with quinine or artesunate for malaria treatment or alone for malaria chemoprophylaxis. Recently, one prophylactic failure has been reported, and several studies have highlighted in vitro doxycycline decreased susceptibility in Plasmodium falciparum isolates from different areas. The genetic markers that contribute to detecting and monitoring the susceptibility of P. falciparum to doxycycline, the pfmdt and pftetQ genes, have recently been identified. However, these markers are not sufficient to explain in vitro decreased susceptibility of P. falciparum to doxycycline. In this paper, the association between polymorphism of the small sub-unit ribosomal RNA apicoplastic gene pfssrRNA (PFC10-API0057) and in vitro susceptibilities of P. falciparum isolates to doxycycline were investigated. Methods: Doxycycline IC<inf>50</inf> determinations using the hypoxanthine uptake inhibition assay were performed on 178 African and Thai P. falciparum isolates. The polymorphism of pfssrRNA was investigated in these samples by standard PCR followed by sequencing. Results: No point mutations were found in pfssrRNA in the Thai or African isolates, regardless of the determined IC<inf>50</inf> values. Conclusions: The pfssrRNA gene is not associated with in vitro decreased susceptibility of P. falciparum to doxycycline. Identifying new in vitro molecular markers associated with reduced susceptibility is needed, to survey the emergence of doxycycline resistance. 2018-11-23T10:15:35Z 2018-11-23T10:15:35Z 2015-09-17 Article Malaria Journal. Vol.14, No.1 (2015) 10.1186/s12936-015-0878-x 14752875 2-s2.0-84941800361 https://repository.li.mahidol.ac.th/handle/123456789/36075 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84941800361&origin=inward |
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Immunology and Microbiology Medicine Tiphaine Gaillard Nathalie Wurtz Sandrine Houzé Kanlaya Sriprawat Chirapat Wangsing Véronique Hubert Jacques Lebras François Nosten Sébastien Briolant Bruno Pradines Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline |
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© 2015 Gaillard et al. Background: Doxycycline is an antibiotic used in combination with quinine or artesunate for malaria treatment or alone for malaria chemoprophylaxis. Recently, one prophylactic failure has been reported, and several studies have highlighted in vitro doxycycline decreased susceptibility in Plasmodium falciparum isolates from different areas. The genetic markers that contribute to detecting and monitoring the susceptibility of P. falciparum to doxycycline, the pfmdt and pftetQ genes, have recently been identified. However, these markers are not sufficient to explain in vitro decreased susceptibility of P. falciparum to doxycycline. In this paper, the association between polymorphism of the small sub-unit ribosomal RNA apicoplastic gene pfssrRNA (PFC10-API0057) and in vitro susceptibilities of P. falciparum isolates to doxycycline were investigated. Methods: Doxycycline IC<inf>50</inf> determinations using the hypoxanthine uptake inhibition assay were performed on 178 African and Thai P. falciparum isolates. The polymorphism of pfssrRNA was investigated in these samples by standard PCR followed by sequencing. Results: No point mutations were found in pfssrRNA in the Thai or African isolates, regardless of the determined IC<inf>50</inf> values. Conclusions: The pfssrRNA gene is not associated with in vitro decreased susceptibility of P. falciparum to doxycycline. Identifying new in vitro molecular markers associated with reduced susceptibility is needed, to survey the emergence of doxycycline resistance. |
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Institut de recherche biomedicale des armees |
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Institut de recherche biomedicale des armees Tiphaine Gaillard Nathalie Wurtz Sandrine Houzé Kanlaya Sriprawat Chirapat Wangsing Véronique Hubert Jacques Lebras François Nosten Sébastien Briolant Bruno Pradines |
format |
Article |
author |
Tiphaine Gaillard Nathalie Wurtz Sandrine Houzé Kanlaya Sriprawat Chirapat Wangsing Véronique Hubert Jacques Lebras François Nosten Sébastien Briolant Bruno Pradines |
author_sort |
Tiphaine Gaillard |
title |
Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline |
title_short |
Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline |
title_full |
Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline |
title_fullStr |
Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline |
title_full_unstemmed |
Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline |
title_sort |
absence of association between plasmodium falciparum small sub-unit ribosomal rna gene mutations and in vitro decreased susceptibility to doxycycline |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/36075 |
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1763491803835662336 |