Permethrin resistance is widespread in Aedes aegypti (L.), the main dengue, zika, and chikungunya virus vector in Latin America and the Caribbean. A common mechanism of resistance to pyrethroids-knockdown resistance (kdr)-is conferred through mutations in the insect's voltage-dependent sodium channel. In this mosquito, around 10 replacement substitutions in the voltage-gated sodium channel gene (vgsc) have been reported in pyrethroid-resistant strains. Two of these mutations, named Ile1,016 and Cys1,534, are widespread in mosquito populations from Latin America and the Caribbean. This study assessed the levels of permethrin resistance and the frequency of two kdr mutations in eight Ae. aegypti populations collected in Puerto Rico in 2013. Permethrin resistance factors ranged from 33-214-fold relative to the New Orleans reference strain. The frequency of kdr mutation Ile1,016 ranged from 0.65 to fixation (1.0), and for Cys1,534 frequencies varied from 0.8 to fixation. Alarmingly, two populations-Carolina and Caguas-reached fixation at both loci. Our results suggest that permethrin effectiveness for Ae. aegypti control is compromised in these collections from Puerto Rico.

Segmental identity along the anteroposterior axis of bilateral animals is specified by Hox genes. These genes encode transcription factors, harboring the conserved homeodomain and, generally, a YPWM motif, which binds Hox cofactors and increases Hox transcriptional specificity in vivo. Here we derive synthetic Drosophila Antennapedia genes, consisting only of the YPWM motif and homeodomain, and investigate their functional role throughout development. Synthetic peptides and full-length Antennapedia proteins cause head-to-thorax transformations in the embryo, as well as antenna-to-tarsus and eye-to-wing transformations in the adult, thus converting the entire head to a mesothorax. This conversion is achieved by repression of genes required for head and antennal development and ectopic activation of genes promoting thoracic and tarsal fates, respectively. Synthetic Antennapedia peptides bind DNA specifically and interact with Extradenticle and Bric-à-brac interacting protein 2 cofactors in vitro and ex vivo. Substitution of the YPWM motif by alanines abolishes Antennapedia homeotic function, whereas substitution of YPWM by the WRPW repressor motif, which binds the transcriptional corepressor Groucho, allows all proteins to act as repressors only. Finally, naturally occurring variations in the size of the linker between the homeodomain and YPWM motif enhance Antennapedia repressive or activating efficiency, emphasizing the importance of linker size, rather than sequence, for specificity. Our results clearly show that synthetic Antennapedia genes are functional in vivo and therefore provide powerful tools for synthetic biology. Moreover, the YPWM motif is necessary-whereas the entire N terminus of the protein is dispensable-for Antennapedia homeotic function, indicating its dual role in transcriptional activation and repression by recruiting either coactivators or corepressors.Hox specificity | synthetic genes | homeotic transformations | antenna-to-tarsus transformation

This study showed that high frequencies of kdr mutations V1016I and F1534C are reflected in the results of F-RDT and I-RDT tests. Bioassays in conjunction with the characterization of genetic resistance mechanisms are indispensable in the strategic and rational management of resistance in mosquitoes. © 2018 Society of Chemical Industry.

Alterations in life parameters could be due to the accumulation of noxious effects or deleterious genes related to detoxifying enzymes, specifically those coding for mixed-function oxidases, along with the presence of recessive alleles of the V1016I and F1534C mutations, associating deltamethrin resistance with fitness cost in Ae. aegypti. © 2017 Society of Chemical Industry.

Aedes aegypti (L.) is the primary vector of the viruses that cause dengue, Zika, and chikungunya, for which effective vaccines and drugs are still lacking. Current strategies for suppressing arbovirus outbreaks based on insecticide use pose a challenge because of the rapid increase in resistance. The widespread and excessive use of pyrethroid-based insecticides has created a large selection pressure for a kdr-type resistance, caused by mutations in the para gene of the voltage-gated sodium channel (vgsc). Our objective was to evaluate the allelic frequency of natural populations of Ae. aegypti of Mexico at codon 410 of the para gene. Twenty-six Ae. aegypti populations from east and southern Mexico were genotyped for the codon 410 using allele-specific PCR. The frequencies of the L410 allele in Ae. aegypti ranged from 0.10 to 0.99; however, most of the frequencies were in the range of 0.36 to 0.64. The highest frequencies were found in three populations from the state of Veracruz, namely, Minatitlan with 0.99, Poza Rica with 0.82, and Jose Cardel with 0.97, along with populations from Cancun in Quintana Roo with 0.93, Frontera in Tabasco with 0.91, and Ciudad del Carmen in Campeche with 0.86. The frequency of the L410 allele was high in all populations of Ae. aegypti with higher values in populations of the southeast of the country. The knowledge of specific substitutions in vgsc and their interaction to confer resistance is essential to predict and develop future strategies for resistance management in Ae. aegypti in Mexico.