Biological Significance of selected Ixodes scapularis Transcription Factors regulating Tick Hematophagy and Development

Abstract

Lyme disease is one of the most prominent vector-borne diseases, which is transmitted by the Ixodes scapularis tick and related species, and the causative agent is the bacterial pathogen Borrelia burgdorferi. Besides I. scapularis, many other tick species are also prolific vectors of several bacterial, viral, or eukaryotic pathogens affecting humans and animals. I. scapularis possess a large genome of 2.26 Gbp, predominantly featuring repetitive DNA or transposomal elements. Although many orthologous genes are present in other arthropods and blood-borne vectors, the genome also encodes numerous unique tick-specific genes. Despite many advances in Ixodes biology and genomics, the molecular basis of their hematophagy and development remains unknown. During feeding on the host, a major tick organ like the gut undergoes remarkable yet poorly understood episodes of cell division and differentiation, accommodating a huge blood meal that can be up to 100-fold greater than their body weight. The gut, therefore, plays a vital role in blood meal acquisition, digestion, and storage, supporting the long-term survival of ticks during prolonged off-host periods of nutrient deprivation. Understanding the molecular mechanism of gut physiology, including cell division and differentiation, is an essential area of research. As transcription factors are central to the biology and development of metazoan organisms yet remain largely uncharacterized in ticks, the goal of this dissertation is to decipher the biological significance of representative groups of major development-associated transcription factors in I. scapularis that are expressed in the gut, especially during blood meal engorgement process. Among them, two of the highly upregulated transcription factors in the gut were chosen for further characterization. We show that both transcription factors, Immunoglobin-fold transcription factor (SuH) and POU domain transcription factor (Nubbin), play essential roles in tick physiology, as their knockdowns impart phenotypic defects, impacting tick feeding, development and life cycle. The latter part of the dissertation will highlight the molecular mechanism of their functions. A fundamental understanding of the molecular basis of tick biology, hematophagy, and development may contribute to developing novel strategies to curb the spread of tick-infection.