Investigations of Lyme spirochete transmission as a complex network of microbial and ecological interactions

点击翻译按钮获取中文摘要

Borrelia burgdorferi (Bb), transmitted via the blacklegged tick (Ixodes scapularis), is of growing public health importance as the etiologic agent of the most prevalent vector-borne disease in North America, Lyme disease (LD), which continues to increase in incidence. Although often framed as a pathogen in the Enzootic Transmission Cycle (ETC), there is no evidence that Bb elicits disease in either the reservoir or tick hosts between which it cycles. Here, we conceptualize Bb-infection in I. scapularis ticks as a facultative mutualism that is influenced by microbial dynamics within ticks and the broader context of ecological interactions between ticks and vertebrate hosts comprising the ETC. Ixodes scapularis is a valuable candidate to study networks of ecological interactions, as its microbiome encompasses the spectrum of relationships in which microbes can engage with arthropod hosts from transitory, commensal environmentally-acquired microbes to heritable obligate, intracellular endosymbionts, the most predominant of which is Rickettsia buchneri (Rb). Focusing on interactions hypothesized to influence the Bb-ETC, the proposed study will characterize Bb colonization in ticks, evaluating changes in Bb abundance and gene expression as a function of the presence of the putative nutritional endosymbiont Rb and the tick microbiome as characterized by 1) the relative abundance of bacterial taxa (16S ribosomal RNA) and 2) manipulated, categorical microbiome assemblages (i.e., natural-field collected ticks; artificial-lab reared; and disrupted-lab reared in sterile-containers (SA1). Bb effects on tick life-history traits, survival, metabolism and behavior and associated gene expression (of Bb and tick) will be measured, estimating the benefits/costs of Bb-tick associations, and testing potential mechanisms (SA2). Finally, the cumulative impacts of within-ticks, tick-microbe, and tick-microbiome interactions (Bb-Rb interactions and categorical assemblages) will be estimated and evaluated for the Bb-ETC using two modeling frameworks. An agent based model will focus on microbe-mediated differences in tick bloodmeal engorgement, development, survival, behavior, and fecundity (SA3.1). A compartmental model of Bb-ETC dynamics over a broader time scale will also consider seasonality across multiple cycles. Models, developed in parallel with and informed by field and lab experiments and empirical data will be leveraged to develop a formal tick vectorial capacity definition inclusive of important components and effects of the tick microbiome (SA3.2). These results then will be leveraged to improve understanding of Bb-ETC and prediction of LD risk indicators.