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Contrasting patterns of gene expression indicate differing pyrethroid resistance mechanisms across the range of the New World malaria vector Anopheles albimanus

Mackenzie-Impoinvil, L, Weedall, GD, Lol, JC, Pinto, J, Vizcaino, L, Dzuris, N, Riveron, J, Padilla, N, Wondji, C and Lenhart, A (2019) Contrasting patterns of gene expression indicate differing pyrethroid resistance mechanisms across the range of the New World malaria vector Anopheles albimanus. PLoS One, 14 (1). ISSN 1932-6203

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Abstract

Decades of unmanaged insecticide use and routine exposure to agrochemicals have left many populations of malaria vectors in the Americas resistant to multiple classes of insecticides, including pyrethroids. The molecular basis of pyrethroid resistance is relatively uncharacterised in American malaria vectors, preventing the design of suitable resistance management strategies. Using whole transcriptome sequencing, we characterized the mechanisms of pyrethroid resistance in Anopheles albimanus from Peru and Guatemala. An. albimanus were phenotyped as either deltamethrin or alpha-cypermethrin resistant. RNA from 1) resistant, 2) unexposed, and 3) a susceptible laboratory strain of An. Albimanus was sequenced and analyzed using RNA-Seq. Expression profiles of the three groups were compared based on the current annotation of the An. albimanus reference genome. Several candidate genes associated with pyrethroid resistance in other malaria vectors were found to be overexpressed in resistant An. albimanus. In addition, gene ontology terms related to serine-type endopeptidase activity, extracellular activity and chitin metabolic process were also commonly overexpressed in the field caught resistant and unexposed samples from both Peru and Guatemala when compared to the susceptible strain. The cytochrome P450 CYP9K1 was overexpressed 14x in deltamethrin and 8x in alpha-cypermethrin-resistant samples from Peru and 2x in deltamethrin-resistant samples from Guatemala, relative to the susceptible laboratory strain. CYP6P5 was overexpressed 68x in deltamethrin-resistant samples from Peru but not in deltamethrin-resistant samples from Guatemala. When comparing overexpressed genes between deltamethrin-resistant and alpha-cypermethrin-resistant samples from Peru, a single P450 gene, CYP4C26, was overexpressed 9.8x (p<0.05) in alpha-cypermethrin-resistant samples. In Peruvian deltamethrin-resistant samples, the knockdown resistance mutation (kdr) variant alleles at position 1014 were rare, with approximately 5% frequency, but in the alpha-cypermethrin-resistant samples, the frequency
of these alleles was approximately 15–30%. Functional validation of the candidate genes and the kdr mutation as a resistance marker for alpha-cypermethrin will confirm the
role of these mechanisms in conferring pyrethroid resistance.

Item Type: Article
Uncontrolled Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; MICROPLATE ASSAY ANALYSIS; SCALE FIELD TRIAL; INSECTICIDE RESISTANCE; MANAGEMENT STRATEGIES; SEQUENCE ALIGNMENT; GAMBIAE; CYTOCHROME-P450; MOSQUITOS; SUSCEPTIBILITY; VISUALIZATION
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
S Agriculture > S Agriculture (General)
Divisions: Biological & Environmental Sciences (new Sep 19)
Publisher: Public Library of Science
Related URLs:
Date Deposited: 03 Oct 2019 09:06
Last Modified: 03 Oct 2019 09:15
DOI or Identification number: 10.1371/journal.pone.0210586
URI: http://researchonline.ljmu.ac.uk/id/eprint/11448

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