Ecological mediators of pyrethroid resistance evolution in Aedes aegypti Pubblico

Abstract

Chemical insecticides are used globally to prevent the transmission of vector-borne pathogens to humans. Due to the strong selective pressures insecticides exert on target vector populations, insecticide resistance has evolved in all major vector species. Resistance is of particular concern for the prevention of dengue, chikungunya, and Zika, diseases that are transmitted by the Aedes aegypti mosquito, since insecticides are currently the only way to prevent and curtail outbreaks. One prevalent form of resistance in Ae. aegypti, called "knock-down resistance" (kdr), confers resistance to pyrethroid insecticides through point mutations in the sodium channel gene. Research on insecticide resistance in Ae. aegypti has largely focused on determining the underlying genes and molecular mechanisms responsible for resistance, and has mostly overlooked the ecological processes that mediate the evolution of resistance. For example, little is known about how resistance genes spread within and between populations, and whether there exists a fitness cost to resistance. These knowledge gaps limit our ability to effectively manage resistance at the population level. The objective of my dissertation is to understand some of the ecological processes underlying resistance evolution in natural populations of Ae. aegypti. Chapter 1 describes the spatial and temporal patterns of kdr allele frequencies in a small city in the Yucatán, Mexico, and shows that allele frequencies are highly heterogeneous between city blocks, a spatial scale that had not been previously assessed. Furthermore, kdr allele frequencies were significantly lower after the dry season, suggesting that there may be a fitness cost to pyrethroid resistance in the absence of strong insecticide pressure. Chapter 2 provides empirical evidence of a fitness cost to pyrethroid resistance in Ae. aegypti, measured through various life history traits, and shows that density-dependent intraspecific competition can mediate resistance phenotype and genotype. Chapter 3 provides further evidence of a fitness cost to resistance and shows that pyrethroid susceptibility can be restored in just over 10 generations without insecticide pressure. These results lend support to vector control strategies that vary insecticide application in time and/or space, leveraging the fitness cost of resistance in the absence of insecticides to regain susceptibility in populations.

Table of Contents

Introduction.............................................................................................................. 1

Chapter 1: Fine-scale spatial and temporal dynamics of knock-down resistance evolution in Aedes aeygpti............................................................................................................................. 7

Introduction.......................................................................................................................... 7

Methods............................................................................................................................. 10

Results............................................................................................................................... 14

Discussion......................................................................................................................... 18

Figures and Tables............................................................................................................. 21

Figure 1.1.......................................................................................................................... 21

Figure 1.2.......................................................................................................................... 22

Table 1.1........................................................................................................................... 22

Figure 1.3.......................................................................................................................... 23

Figure 1.4.......................................................................................................................... 23

Figure 1.5.......................................................................................................................... 24

Figure 1.6.......................................................................................................................... 25

Figure 1.7.......................................................................................................................... 26

Figure 1.9.......................................................................................................................... 28

Figure 1.10........................................................................................................................ 29

References.......................................................................................................................... 29

Supplemental Information.................................................................................................. 35

Table S1.1......................................................................................................................... 35

Table S1.2......................................................................................................................... 35

Table S1.3......................................................................................................................... 36

Table S1.4......................................................................................................................... 37

Table S1.5......................................................................................................................... 37

Table S1.6......................................................................................................................... 37

Table S1.7......................................................................................................................... 38

Table S1.8......................................................................................................................... 38

Table S1.9......................................................................................................................... 38

Table S1.10....................................................................................................................... 38

Table S1.11....................................................................................................................... 39

Table S1.12....................................................................................................................... 39

Figure S1.1........................................................................................................................ 40

Chapter 2: Intraspecific competition mediates evolution of insecticide resistance in Aedes aegypti 41

Introduction........................................................................................................................ 41

Methods............................................................................................................................. 44

Results............................................................................................................................... 49

Discussion......................................................................................................................... 52

Figures and Tables............................................................................................................. 57

Table 2.1........................................................................................................................... 57

Figure 2.2.......................................................................................................................... 59

Figure 2.4.......................................................................................................................... 61

Figure 2.5.......................................................................................................................... 62

References.......................................................................................................................... 62

Supplementary information................................................................................................ 65

Table S2.1......................................................................................................................... 65

Figure S2.1........................................................................................................................ 66

Figure S2.2........................................................................................................................ 67

Table S2.2......................................................................................................................... 68

Table S2.3......................................................................................................................... 68

Table S2.4......................................................................................................................... 68

Chapter 3: Selection dynamics of the knock-down resistant mutations in Aedes aegypti 69

Introduction........................................................................................................................ 69

Methods............................................................................................................................. 71

Results............................................................................................................................... 74

Discussion......................................................................................................................... 77

Figures and Tables............................................................................................................. 80

Figure 3.1.......................................................................................................................... 80

Figure 3.2.......................................................................................................................... 81

Table 3.1........................................................................................................................... 81

Figure 3.3.......................................................................................................................... 82

References.......................................................................................................................... 82

Conclusion................................................................................................................. 87

About this Dissertation

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Subfield / Discipline	Population Biology, Ecology & Evolution
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Biology, Evolution and Development Biology, Ecology Biology, Entomology
Parola chiave	pyrethroid insecticides Aedes aegypti Insecticide resistance knock-down resistance
Committee Chair / Thesis Advisor	Vazquez Prokopec, Gonzalo, Emory University
Committee Members	Brosi, Berry J, Emory University Waller, Lance, Emory University Zwick, Michael, Emory University Morran, Levi T, Emory University

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