Molecular Drivers of Multiple and Elevated Resistance to Insecticides in a Population of the Malaria Vector Anopheles gambiae in Agriculture Hotspot of West Cameroon

被引:17
作者
Tepa, Arnaud [1 ,2 ]
Kengne-Ouafo, Jonas A. [1 ]
Djova, Valdi S. [1 ,3 ]
Tchouakui, Magellan [1 ]
Mugenzi, Leon M. J. [1 ]
Djouaka, Rousseau [4 ]
Pieme, Constant A. [2 ]
Wondji, Charles S. [1 ,5 ,6 ]
机构
[1] Ctr Res Infect Dis CRID, Med Entomol Dept, POB 13591, Yaounde, Cameroon
[2] Univ Yaounde I, Fac Med & Biomed Sci, Dept Biochem, POB 1364, Yaounde, Cameroon
[3] Univ Bamenda, Dept Biochem, POB 39, Bambili, Cameroon
[4] Int Inst Trop Agr, POB 0932, Cotonou, Benin
[5] Int Inst Trop Agr, POB 2008, Yaounde, Cameroon
[6] Univ Liverpool Liverpool Sch Trop Med, Vector Biol Dept, Pembroke Pl, Liverpool L3 5QA, Merseyside, England
基金
英国惠康基金;
关键词
Anopheles gambiae; Cameroon; malaria; pyrethroids; resistance escalation; cytochrome P450s; PYRETHROID RESISTANCE; MECHANISMS; SELECTION; SEQUENCE; COLUZZII; YAOUNDE;
D O I
10.3390/genes13071206
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
(1) Background: Malaria remains a global public health problem. Unfortunately, the resistance of malaria vectors to commonly used insecticides threatens disease control and elimination efforts. Field mosquitoes have been shown to survive upon exposure to high insecticide concentrations. The molecular mechanisms driving this pronounced resistance remain poorly understood. Here, we elucidated the pattern of resistance escalation in the main malaria vector Anopheles gambiae in a pesticide-driven agricultural hotspot in Cameroon and its impact on vector control tools; (2) Methods: Larval stages and indoor blood-fed female mosquitoes (F-0) were collected in Mangoum in May and November and forced to lay eggs; the emerged mosquitoes were used for WHO tube, synergist and cone tests. Molecular identification was performed using SINE PCR, whereas TaqMan-based PCR was used for genotyping of L1014F/S and N1575Y kdr and the G119S-ACE/ resistance markers. The transcription profile of candidate resistance genes was performed using qRT-PCR methods. Characterization of the breeding water and soil from Mangoum was achieved using the HPLC technique; (3) Results: An. gambiae s.s. was the only species in Mangoum with 4.10% infection with Plasmodium. These mosquitoes were resistant to all the four classes of insecticides with mortality rates <7% for pyrethroids and DDT and <54% for carbamates and organophophates. This population also exhibited high resistance intensity to pyrethroids (permethrin, alpha-cypermethrin and deltamethrin) after exposure to 5 x and 10 x discriminating doses. Synergist assays with PBO revealed only a partial recovery of susceptibility to permethrin, alpha-cypermethrin and deltamethrin. Only PBO-based nets (Olyset plus and permaNet 3.0) and Royal Guard showed an optimal efficacy. A high amount of alpha-cypermethrin was detected in breeding sites (5.16-fold LOD) suggesting ongoing selection from agricultural pesticides. The 1014F-kdr allele was fixed (100%) whereas the 1575Y-kdr (37.5%) and the 119S Ace-1(R) (51.1%) were moderately present. Elevated expression of P450s, respectively, in permethrin and deltamethrin resistant mosquitoes LCYP6M2 (10 and 34-fold), CYP6Z1(17 and 29-fold), CYP6Z2 (13 and 65-fold), CYP9K1 (13 and 87-fold)] supports their role in the observed resistance besides other mechanisms including chemosensory genes as SAP1 (28 and 13-fold), SAP2 (5 and 5-fold), SAP3 (24 and 8-fold) and cuticular genes as CYP4G16 (6 and 8-fold) and CYP4G17 (5 and 27-fold). However, these candidate genes were not associated with resistance escalation as the expression levels did not differ significantly between 1 x, 5 x and 10 x surviving mosquitoes; (4) Conclusions: Intensive and multiple resistance is being selected in malaria vectors from a pesticide-based agricultural hotspot of Cameroon leading to loss in the efficacy of pyrethroid-only nets. Further studies are needed to decipher the molecular basis underlying such resistance escalation to better assess its impact on control interventions.
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页数:17
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