Low polymorphisms in pfact, pfugt and pfcarl genes in African Plasmodium falciparum isolates and absence of association with susceptibility to common anti-malarial drugs.
Anti-malarial drug
In vitro
Malaria
Molecular marker
PfACT
PfCARL
PfUGT
Plasmodium falciparum
Resistance
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
28 Aug 2019
28 Aug 2019
Historique:
received:
22
03
2019
accepted:
17
08
2019
entrez:
29
8
2019
pubmed:
29
8
2019
medline:
18
12
2019
Statut:
epublish
Résumé
Resistance to all available anti-malarial drugs has emerged and spread including artemisinin derivatives and their partner drugs. Several genes involved in artemisinin and partner drugs resistance, such as pfcrt, pfmdr1, pfK13 or pfpm2, have been identified. However, these genes do not properly explain anti-malarial drug resistance, and more particularly clinical failures observed in Africa. Mutations in genes encoding for Plasmodium falciparum proteins, such as P. falciparum Acetyl-CoA transporter (PfACT), P. falciparum UDP-galactose transporter (PfUGT) and P. falciparum cyclic amine resistance locus (PfCARL) have recently been associated to resistance to imidazolopiperazines and other unrelated drugs. Mutations on pfugt, pfact and pfcarl were characterized on 86 isolates collected in Dakar, Senegal and 173 samples collected from patients hospitalized in France after a travel in African countries from 2015 and 2016 to assess their potential association with ex vivo susceptibility to chloroquine, quinine, lumefantrine, monodesethylamodiaquine, mefloquine, dihydroartemisinin, artesunate, doxycycline, pyronaridine and piperaquine. No mutations were found on the genes pfugt and pfact. None of the pfcarl described mutations were identified in these samples from Africa. The K784N mutation was found in one sample and the K734M mutation was identified on 7.9% of all samples for pfcarl. The only significant differences in ex vivo susceptibility according to the K734M mutation were observed for pyronaridine for African isolates from imported malaria and for doxycycline for Senegalese parasites. No evidence was found of involvement of these genes in reduced susceptibility to standard anti-malarial drugs in African P. falciparum isolates.
Sections du résumé
BACKGROUND
BACKGROUND
Resistance to all available anti-malarial drugs has emerged and spread including artemisinin derivatives and their partner drugs. Several genes involved in artemisinin and partner drugs resistance, such as pfcrt, pfmdr1, pfK13 or pfpm2, have been identified. However, these genes do not properly explain anti-malarial drug resistance, and more particularly clinical failures observed in Africa. Mutations in genes encoding for Plasmodium falciparum proteins, such as P. falciparum Acetyl-CoA transporter (PfACT), P. falciparum UDP-galactose transporter (PfUGT) and P. falciparum cyclic amine resistance locus (PfCARL) have recently been associated to resistance to imidazolopiperazines and other unrelated drugs.
METHODS
METHODS
Mutations on pfugt, pfact and pfcarl were characterized on 86 isolates collected in Dakar, Senegal and 173 samples collected from patients hospitalized in France after a travel in African countries from 2015 and 2016 to assess their potential association with ex vivo susceptibility to chloroquine, quinine, lumefantrine, monodesethylamodiaquine, mefloquine, dihydroartemisinin, artesunate, doxycycline, pyronaridine and piperaquine.
RESULTS
RESULTS
No mutations were found on the genes pfugt and pfact. None of the pfcarl described mutations were identified in these samples from Africa. The K784N mutation was found in one sample and the K734M mutation was identified on 7.9% of all samples for pfcarl. The only significant differences in ex vivo susceptibility according to the K734M mutation were observed for pyronaridine for African isolates from imported malaria and for doxycycline for Senegalese parasites.
CONCLUSION
CONCLUSIONS
No evidence was found of involvement of these genes in reduced susceptibility to standard anti-malarial drugs in African P. falciparum isolates.
Identifiants
pubmed: 31455301
doi: 10.1186/s12936-019-2919-3
pii: 10.1186/s12936-019-2919-3
pmc: PMC6712813
doi:
Substances chimiques
Antimalarials
0
Protozoan Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
293Subventions
Organisme : Délégation Générale pour l'Armement
ID : PDH-2-NRBC-4-B-4104
Organisme : Schéma directeur paludisme Etat major des armées
ID : LR 607
Organisme : Santé Publique France
ID : CNR Paludisme
Investigateurs
V Augis
(V)
D Basset
(D)
P Bastien
(P)
F Benoit-Vical
(F)
A Berry
(A)
P Brouqui
(P)
M Cividin
(M)
P Delaunay
(P)
L Delhaes
(L)
M Drancourt
(M)
T Gaillard
(T)
A Genin
(A)
E Garnotel
(E)
E Javelle
(E)
C L'Ollivier
(C)
M Leveque
(M)
D Malvy
(D)
P Marty
(P)
M Mechain
(M)
G Ménard
(G)
P Millet
(P)
P Minodier
(P)
A Mottard
(A)
P Parola
(P)
R Piarroux
(R)
C Pomares-Estran
(C)
M-C Receveur
(MC)
A Robin
(A)
E Sappa
(E)
H Savini
(H)
F Simon
(F)
Y Sterkers
(Y)
C Surcouf
(C)
E Varlet
(E)
A Wolff
(A)
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