Version 2 2023-02-02, 17:05Version 2 2023-02-02, 17:05
Version 1 2023-01-26, 19:07Version 1 2023-01-26, 19:07
journal contribution
posted on 2023-02-02, 17:05authored byKaiyang Liu, Shuyue Ma, Kun Zhang, Ruibo Gao, Haifeng Jin, Peng Cao, Zhiguang Yuchi, Shaoying Wu
The
effectiveness of pyrethroid insecticides is seriously threatened
by knockdown resistance (kdr), which is induced in
insects by inherited single-nucleotide polymorphisms in the voltage-gated
sodium channel (VGSC) gene. VGSC’s L1014F substitution results
in the classic kdr mutation, which is found in many
pest species. Other substitutions of the L1014 locus, such as L1014S,
L1014C, L1014W, and L1014H, were also reported. In 2022, a new amino
acid substitute L1014S of Blattella germanica was first discovered in China. We modified the BgNav1-1
sodium channel from cockroaches with the L1014S mutation to study
how pyrethroid sensitivity and channel gating were affected in Xenopus oocytes. The L1014S mutation reduced the half-maximal
activation voltage (V1/2,act) from −19.0
(wild type) to −15.5 mV while maintaining the voltage dependency
of activation. Moreover, the voltage dependence of inactivation in
the hyperpolarizing shifts from −48.3 (wild type) to −50.9
mV. However, compared with wild type, the mutation L1014S did not
cause a significant shift in the half activation voltage (V1/2,act). Notably, the voltage dependency of
activation was unaffected greatly by the L1014S mutation. Tail currents
are induced by two types of pyrethroids (1 μM): type I (permethrin,
bifenthrin) and type II (deltamethrin, λ-cyhalothrin). All four
pyrethroids produced tail currents, and significant differences were
found in the percentages of channel modifications between variants
and wild types. Further computer modeling showed that the L1014S mutation
allosterically modifies pyrethroid binding and action on B. germanica VGSC, with some residues playing a critical
role in pyrethroid binding. This study elucidated the pyrethroid resistance
mechanism of B. germanica and predicted
the residues that may confer the risk of pyrethroid resistance, providing
a molecular basis for understanding the resistance mechanisms conferred
by mutations at the 1014 site in VGSC.