Suchergebnisse

BACKGROUND: To combat malaria transmission, the Ugandan government has embarked upon an ambitious programme of indoor residual spraying (IRS) with a carbamate class insecticide, bendiocarb. In preparation for this campaign, we characterized bendiocarb resistance and associated transcriptional variation among Anopheles gambiae s.s. mosquitoes from two sites in Uganda. RESULTS: Gene expression in two mosquito populations displaying some resistance to bendiocarb (95% and 79% An. gambiae s.l. WHO tube bioassay mortality in Nagongera and Kihihi, respectively) was investigated using whole-genome microarrays. Significant overexpression of several genes encoding salivary gland proteins, including D7r2 and D7r4, was detected in mosquitoes from Nagongera. In Kihihi, D7r4, two detoxification-associated genes (Cyp6m2 and Gstd3) and an epithelial serine protease were among the genes most highly overexpressed in resistant mosquitoes. Following the first round of IRS in Nagongera, bendiocarb-resistant mosquitoes were collected, and real-time quantitative PCR analyses detected significant overexpression of D7r2 and D7r4 in resistant mosquitoes. A single nucleotide polymorphism located in a non-coding transcript downstream of the D7 genes was found at a significantly higher frequency in resistant individuals. In silico modelling of the interaction between D7r4 and bendiocarb demonstrated similarity between the insecticide and serotonin, a known ligand of D7 proteins. A meta-analysis of published microarray studies revealed a recurring association between D7 expression and insecticide resistance across Anopheles species and locations. CONCLUSIONS: A whole-genome microarray approach identified an association between novel insecticide resistance candidates and bendiocarb resistance in Uganda. In addition, a single nucleotide polymorphism associated with this resistance mechanism was discovered. The use of such impartial screening methods allows for discovery of resistance candidates that have no previously-ascribed function in insecticide binding or detoxification. Characterizing these novel candidates will broaden our understanding of resistance mechanisms and yield new strategies for combatting widespread insecticide resistance among malaria vectors.

Background: The Government of Senegal has initiated the ''Projet de lutte contre les glossines dans les Niayes'' to remove the trypanosomosis problem from this area in a sustainable way. Due to past failures to sustainably eradicate Glossina palpalis gambiensis from the Niayes area, controversies remain as to the best strategy implement, i.e. ''eradication'' versus ''suppression.'' To inform this debate, we used population genetics to measure genetic differentiation between G. palpalis gambiensis from the Niayes and those from the southern tsetse belt (Missira). Methodology/Principal Findings: Three different markers (microsatellite DNA, mitochondrial CO1 DNA, and geometric morphometrics of the wings) were used on 153 individuals and revealed that the G. p. gambiensis populations of the Niayes were genetically isolated from the nearest proximate known population of Missira. The genetic differentiation measured between these two areas (h = 0.12 using microsatellites) was equivalent to a between-taxa differentiation. We also demonstrated that within the Niayes, the population from Dakar - Hann was isolated from the others and had probably experienced a bottleneck. Conclusion/Significance: The information presented in this paper leads to the recommendation that an eradication strategy for the Niayes populations is advisable. This kind of study may be repeated in other habitats and for other tsetse species to (i) help decision on appropriate tsetse control strategies and (ii) find other possible discontinuities in tsetse distribution.