HPPD: A Druggable Metabolic Node in Blood-Feeding Arthropods

Mgr. Matěj KUČERA

Disertační práce

Abstract:

The present doctoral thesis addresses vector-borne diseases and explores novel chemical control strategies targeting blood-feeding arthropods, including mosquitoes and ticks. The research is motivated by the pressing need for selective, efficient, and sustainable interventions in the face of rising resistance to conventional insecticides. The primary focus is the biochemical and molecular characterization of the tyrosine degradation pathway and its key enzyme, 4-hydroxyphenylpyruvate dioxygenase (HPPD), as a potential target for vector control. The thesis integrates a literature review of vector physiology, blood digestion mechanisms, and pigment biosynthesis pathways in arthropods, highlighting how tyrosine-derived metabolites contribute to cuticle formation, pigmentation, and survival. Using a combination of biochemical assays, molecular analyses, and analytical chemistry, the work investigates the susceptibility of blood feeders to HPPD inhibition. The work of this thesis demonstrates that pharmacological targeting of HPPD disrupts tyrosine metabolism, leading to impaired pigment formation, developmental arrest, and increased mortality in blood-feeding arthropods. These findings confirm HPPD as a druggable enzyme and reveal a mechanistic link between metabolic pathways and physiological vulnerability in vectors. The scientific novelty of this thesis lies in establishing HPPD inhibition as a selective strategy for controlling disease vectors, offering an alternative to neurotoxic insecticides and growth regulators. The work also provides comparative insights into pigment biosynthesis pathways, evolutionary diversity, and potential molecular targets across arthropod species. Practically, the findings suggest avenues for designing selective inhibitors with minimal off-target effects, contributing to integrated vector management strategies.

Abstract:

The present doctoral thesis addresses vector-borne diseases and explores novel chemical control strategies targeting blood-feeding arthropods, including mosquitoes and ticks. The research is motivated by the pressing need for selective, efficient, and sustainable interventions in the face of rising resistance to conventional insecticides. The primary focus is the biochemical and molecular characterization of the tyrosine degradation pathway and its key enzyme, 4-hydroxyphenylpyruvate dioxygenase (HPPD), as a potential target for vector control. The thesis integrates a literature review of vector physiology, blood digestion mechanisms, and pigment biosynthesis pathways in arthropods, highlighting how tyrosine-derived metabolites contribute to cuticle formation, pigmentation, and survival. Using a combination of biochemical assays, molecular analyses, and analytical chemistry, the work investigates the susceptibility of blood feeders to HPPD inhibition. The work of this thesis demonstrates that pharmacological targeting of HPPD disrupts tyrosine metabolism, leading to impaired pigment formation, developmental arrest, and increased mortality in blood-feeding arthropods. These findings confirm HPPD as a druggable enzyme and reveal a mechanistic link between metabolic pathways and physiological vulnerability in vectors. The scientific novelty of this thesis lies in establishing HPPD inhibition as a selective strategy for controlling disease vectors, offering an alternative to neurotoxic insecticides and growth regulators. The work also provides comparative insights into pigment biosynthesis pathways, evolutionary diversity, and potential molecular targets across arthropod species. Practically, the findings suggest avenues for designing selective inhibitors with minimal off-target effects, contributing to integrated vector management strategies.

Keywords

vector-borne diseases, blood-feeding arthropods, tyrosine degradation, HPPD, pigment biosynthesis, chemical control, insecticide resistance, haem

Jazyk práce: angličtina

Datum vytvoření / odevzdání či podání práce: 15. 4. 2026

Obhajoba závěrečné práce

• Vedoucí: Mgr. Jan Perner, Ph.D.

JIHOČESKÁ UNIVERZITA V ČESKÝCH BUDĚJOVICÍCH

Přírodovědecká fakulta

Doktorský studijní program / obor:
Integrativní biologie / Integrativní biologie