Exploring the Effects of Inequities in Treatment Access on Resistance Emergence in C. elegans.
Open Access
- Author:
- Aluquin, Anton
- Area of Honors:
- Immunology and Infectious Disease
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- David A Kennedy, Thesis Supervisor
Robert Paulson, Thesis Honors Advisor - Keywords:
- antimicrobial resistance
Caenorhabditis elegans
health inequities
treatment access
resistance evolution
experimental evolution - Abstract:
- Antimicrobial resistance is a problem of increasing global concern. Access to proper treatments such as antimicrobial drugs and vaccines is one way by which we can mitigate the disease burden of these resistant infections. However, inequitable and patchwork treatment of these infections at the individual and population level may impose serious consequences for the severity of this growing problem. While there have been observational and epidemiological studies documenting the effects of differences in antimicrobial prescription rates as well as differences in antimicrobial resistant disease burden between advantaged and disadvantaged groups, experimental studies involving inequitable access on drug resistance have only been investigated through the lens of host jumps. Previous work in bacterial models has established evolving bacteriophages in mixed populations of susceptible and non-susceptible bacterial strains, resulting in the bacteriophage better infecting the non-susceptible hosts. While the effects of intermediate population ratios on host jump have been studied, the effects of intermediate population ratios on the resistance evolution dynamics of a pathogen to a therapeutic treatment have not been well documented. This thesis investigates the effects of intermediate population ratios on treatment resistance emergence in Caenorhabditis elegans and its recently discovered natural pathogen Orsay virus. Using a treatment that primes the RNA-interference response of C. elegans, various population ratios of RNAi-treated strains and non-RNAi-treated strains were mixed and infected with Orsay virus. This virus was passage through 10 sequential generations of worm populations. A modified Tissue Culture Infectious Dose 50 assay was then used to assess the 10th passage virus’s relative resistance to the treatment. We hypothesize that intermediate ratios will lend to an increased emergence of treatment resistance in the virus populations, due to the combined effects of maximum selection pressure with the maximum amount of available susceptible hosts. The results of this experiment present suggestive evidence to support this hypothesis, showing a suggestive significant increase in the model estimate average of the 20% group compared to the 0% and 100%. However, skewed omission of undefined TCID50 measures, and the high variation of the data muddle the relationship that was expected. Continuing the experiment with more passages and documenting the other effects on the fitness of the virus will help further explore the work done here on the relationship between health inequities and antimicrobial resistance.