Student Theses and Dissertations

Date of Award

2015

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Vosshall Laboratory

Abstract

Aedes aegypti mosquitoes are the principal vectors of two major infectious diseases that plague the developing world today: dengue fever and chikungunya, with dengue fever alone resulting in ~400 million total yearly infections, and ~24,000 deaths (Bhatt et al., 2013). Understanding the biology behind Ae. aegypti attraction to humans is critical for developing novel strategies to combat these diseases. Yet, even the basic act of how mosquitoes choose one human host over another is poorly understood. Many previous studies on differential attraction have focused on small, homogenous subject populations and addressed a single hypothesis. We took the opposite strategy and studied a large, diverse 150-subject cohort, capturing a multitude of variables that may be involved in host selection. Importantly, our study examined the previously unexplored possibility that mosquito preference may be correlated with differences blood metabolites between subjects. We developed the uniport olfactometer as a method for discriminating subject attraction. Within our study population we distinguished three clusters of subjects who were differentially attractive to mosquitoes. We performed metabolic profiling with subject plasma samples and acquired relative concentrations of 613 different metabolites. We also collected information pertaining to 41 other variables including demographic information, self-reported lifestyle factors, self-reported reaction to mosquito bites, vital signs, blood type, a complete blood count panel, and clinical blood analysis. Using a variety of statistical methods for feature selection, we narrowed this list of variables and arrived at two preliminary models for mosquito attraction. These models explain 24.1% of subject variation in mosquito attraction, and approximately 19.7% of this explanatory power is due to blood metabolites alone. Metabolites within the amino acid superpathway, and specifically the histidine subpathway were negatively correlated with mosquito attraction. Conversely, molecules within the lipid metabolism superpathway, specifically long chain fatty acids and monoacylglycerols, were positively correlated with mosquito attraction. This is the first study to correlate human blood metabolomic components with selective attraction of mosquitoes to hosts. Our work establishes a framework to study the causality of these correlates, and determine the mechanisms underlying their effect on mosquito choice.

Comments

A Thesis Presented to the Faculty of The Rockefeller University In Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

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