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

Mackenzie-Impoinvil, Lucy, Weedall, Gareth ORCID: https://orcid.org/0000-0002-8927-1063, Lol, Juan C, Pinto, Jesus, Vizcaino, Lucrecia, Dzuris, Nicole, Riveron, Jacob ORCID: https://orcid.org/0000-0002-5395-767X, Padilla, Norma, Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673 and Lenhart, Audrey (2019) 'Contrasting patterns of gene expression indicate differing pyrethroid resistance mechanisms across the range of the New World malaria vector Anopheles albimanus'. PLoS ONE, Vol 14, Issue 1.

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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
Subjects:	QU Biochemistry > Genetics > QU 450 General Works QU Biochemistry > Genetics > QU 470 Genetic structures QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.pone.0210586
Depositing User:	Stacy Murtagh
Date Deposited:	04 Feb 2019 11:53
Last Modified:	13 Sep 2019 15:48
URI:	https://archive.lstmed.ac.uk/id/eprint/10019

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