Mechanisms Affecting the Acquisition, Persistence and Transmission of Francisella tularensis in Ticks

Abstract

Over 600,000 vector-borne disease cases were reported in the United States (U.S.) in the past 13 years, of which more than three-quarters were tick-borne diseases. Although Lyme disease accounts for the majority of tick-borne disease cases in the U.S., tularemia cases have been increasing over the past decade, with >220 cases reported yearly. However, when comparing Borrelia burgdorferi (causative agent of Lyme disease) and Francisella tularensis (causative agent of tularemia), the low infectious dose (<10 bacteria), high morbidity and mortality rates, and potential transmission of tularemia by multiple tick vectors have raised national concerns about future tularemia outbreaks. Despite these concerns, little is known about how F. tularensis is acquired by, persists in, or is transmitted by ticks. Moreover, the role of one or more tick vectors in transmitting F. tularensis to humans remains a major question. Finally, virtually no studies have examined how F. tularensis adapts to life in the tick (vs. the mammalian host), how tick endosymbionts affect F. tularensis infections, or whether other factors (e.g., tick immunity) impact the ability of F. tularensis to infect ticks. This review will assess our current understanding of each of these issues and will offer a framework for future studies, which could help us better understand tularemia and other tick-borne diseases.

Keywords: Francisella tularensis; tick-borne disease; tularemia.

Figure 1

Possible factors affecting F. tularensis infection, persistence, and transmission in ticks. Ticks acquire F. tularensis (Ft) by taking a blood meal from an infected host (e.g., mouse, cat, squirrel, vole, rabbit, or opossum). Upon infecting ticks, F. tularensis likely regulates gene expression based on changes in temperature (37 to 27 °C) and iron (low to high). Following processing of the blood meal, nutrients are likely limited in the tick. However, during the tick molting process, chitin fragments may be made available via chitin remodeling and/or breakdown of the peritrophic matrix. Subsequently, F. tularensis must overwinter in ticks, a process which may require biofilm formation, evasion/modulation of the tick immune system, and/or interactions with tick endosymbionts. However, previous studies have not examined any of these factors. Upon transmission from infected ticks to a new mammalian host, F. tularensis likely senses mammalian cues (e.g., increased temperature, low iron, higher concentrations of amino acids) and may alter its gene expression, including virulence genes, to promote infection. Figure created using Biorender.com.