Cross resistance to brevetoxin-3 by kdr and super-kdr mutations in house flies.

Autor: Swale DR; Emerging Pathogens Institute, Department of Entomology and Nematology, University of Florida, Gainesville, FL, 32610, USA. Electronic address: dswale@epi.ufl.edu., Bloomquist JR; Emerging Pathogens Institute, Department of Entomology and Nematology, University of Florida, Gainesville, FL, 32610, USA., McComic SE; Emerging Pathogens Institute, Department of Entomology and Nematology, University of Florida, Gainesville, FL, 32610, USA., Burgess ER 4th; Emerging Pathogens Institute, Department of Entomology and Nematology, University of Florida, Gainesville, FL, 32610, USA.
Jazyk: angličtina
Zdroj: Pesticide biochemistry and physiology [Pestic Biochem Physiol] 2024 May; Vol. 201, pp. 105898. Date of Electronic Publication: 2024 Apr 08.
DOI: 10.1016/j.pestbp.2024.105898
Abstrakt: The dinoflagellate Karenia brevis is a causative agent of red tides in the Gulf of Mexico and generates a potent family of structurally related brevetoxins that act via the voltage-sensitive Na + channel. This project was undertaken to better understand the neurotoxicology and kdr cross-resistance to brevetoxins in house flies by comparing the susceptible aabys strain to ALkdr (kdr) and JPskdr (super-kdr). When injected directly into the hemocoel, larvae exhibited rigid, non-convulsive paralysis consistent with prolongation of sodium channel currents, the known mechanism of action of brevetoxins. In neurophysiological studies, the firing frequency of susceptible larval house fly central nervous system preparations showed a > 200% increase 10 min after treatment with 1 nM brevetoxin-3. This neuroexcitation is consistent with the spastic paralytic response seen after hemocoel injections. Target site mutations in the voltage-sensitive sodium channel of house flies, known to confer knockdown resistance (kdr and super-kdr) against pyrethroids, attenuated the effect of brevetoxin-3 in baseline firing frequency and toxicity assays. The rank order of sensitivity to brevetoxin-3 in both assays was aabys > ALkdr > JPskdr. At the LD 50 level, resistance ratios for the knockdown resistance strains were 6.9 for the double mutant (super-kdr) and 2.3 for the single mutant (kdr). The data suggest that knockdown resistance mutations may be one mechanism by which flies survive brevetoxin-3 exposure during red tide events.
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Databáze: MEDLINE