Ecotope-Based Entomological Surveillance and Molecular Xenomonitoring of Multidrug Resistant Malaria Parasites in Anopheles Vectors

Table 1

Putative drug resistance genes as molecular markers for molecular xenomonitoring of MDR malaria parasites in Anopheles vectors.

Class/antimalarial drugs^a—specific resistance	Annotated drug resistance protein	Annotated orthologous gene	Accession number^g	Reference
Quinolines and derivatives	Chloroquine resistance; transporter^b	Pfcrt	AF030694	[55, 56]
Chloroquine, primaquine, amodiaquine,			AF495378	[57]
and mefloquine		Pvcrt	AF314649	[58]
Cinchona alkaloids			EU333972	[59]
Quinine
Phenanthrenes and derivatives
Halofantrine, lumefantrine
Quinolines and derivatives	Multidrug resistance protein^b	Pfmdr 1	M29154	[60]
Amodiaquine, mefloquine			FJ477805	[61]
Phenanthrenes and derivatives		Pvmdr 1	EU333979	[59]
Lumefantrine	Calcium-dependent	Pfatp6	AB576306	[62]
Sequiterpene lactone	sarcoplasmic/endoplasmic		KC577117	[63]
Artemisinin and derivatives (artesunate,	reticulum ATPase^b
artemether)	GTP-cyclohydrolase I^b	Pfgch 1	AF043557	[64]
Artemisinin-based combination therapies^d	K13-propeller (Kelch protein)^c	PF13_0238	AL844509
(artesunate-amodiaquine, artesunate-			XM001350122
mefloquine, and artemether-lumefantrine)
Diazines	Dihydrofolate reductase^e	Pfdhfr	J03028	[65]
Pyrimethamine			J03772	[66]
Benzene and derivatives		Pvdhfr	X98123	[67]
Proguanil			DQ514918	[68]
Benzene and derivatives	Dihydropteroate synthase^e	Pfdhps	Z231584	[69]
Sulfadoxine			U07706	[70]
		Pvdhps	AY186730	[71]
Acenes and derivatives	Cytochrome	Pfcytb	M9946	[72]
Atovaquone, atovaquone-proguanil		Pvcytb	AF055587	[73]

Further details are available at websites: PubChem, http://pubchem.ncbi.nlm.nih.gov/; and DrugBank, http://www.drugbank.ca/.
Molecular mechanism for resistance: ^bintraparasitic pumps involved in modulation of transporting the drugs across the membranes; ^emetabolic enzymes involved in decreased selectivity of antifolates and sulfonamides; and ^fcytochrome bc₁ complex (complex III) involved in decreased selectivity of mitochondrial electron transport inhibitors or ubiquinone analogs.
^cP. falciparum Kelch protein (encoded by a locus PF13_0238) conferring a single point mutation at the position Met476Ile is involved in molecular mechanism for artemisinin resistance [74] as its propensity to the mutation is believed to be the result of the selection under pressures of ^dACTs.
^gComplete genomic DNA sequences served as molecular markers of which design of specific primer sets has been used in monitoring MDR falciparum or vivax malaria parasites present in the patients or Anopheles vectors and assessing treatment failure in the patients.