Disruption of chitin synthases impairs tick feeding and reproduction, validating a broad-spectrum acaricide target

Chitin, a major structural component of arthropods, is synthesized by chitin synthases (CHSs), which polymerize N-acetylglucosamine and extrude chitin into the extracellular matrix. CHSs are essential for cuticle formation and peritrophic matrix (PM) biogenesis and represent validated targets of several acaricides, yet their roles in ticks remain poorly defined. Here, we functionally characterize CHSs in the tick Ixodes ricinus, a major European vector of Lyme borreliosis. We identify three CHS genes with distinct expression patterns. RNA interference-mediated silencing of individual CHS genes reduced chitin deposition in the cuticle and PM, impaired feeding, survival, molting, and oviposition, and caused high post-feeding mortality. Artificial feeding with etoxazole, a non-catalytic CHS inhibitor, phenocopied these defects at nanomolar concentrations. While CHS silencing did not affect Borrelia afzelii transmission, it increased pathogen acquisition by feeding nymphs. Together, our findings establish CHSs as essential regulators of tick physiology and highlight their potential as selective molecular targets for tick control strategies.