Investigating in vivo and in vitro trade-offs of antifungal resistance in Candida albicans Open Access

Abstract

Biological trade-offs occur when an adaptive trait comes at the cost of another. In microbes, it has historically been thought that resistance to antifungals and antibiotics comes with costs to traits such as growth and virulence. However, recent work demonstrates that antibiotic resistance can often come at no cost to the organism, suggesting there may not be trade-offs due to resistance. As well, it remains largely unknown if there are trade-offs with drug resistance in fungal pathogens such as Candida albicans. Here, I measured the growth rates and virulence of caspofungin resistant C. albicans in the absence of antifungal. Our results show that caspofungin resistant C. albicans did not have attenuated in vitro growth rates or virulence in a C. elegans host compared to susceptible C. albicans. I also measured the minimum inhibitory concentrations (MIC) of C. albicans to another common antifungal fluconazole to determine if evolution in caspofungin conferred an advantage in cross-adaptation. Interestingly, evolved tetraploids, but not diploids were better adapted to fluconazole than ancestral C. albicans. Together, this work demonstrates that caspofungin resistance does not at a cost to growth and virulence in C. albicans and that long term evolution in caspofungin in tetraploids allows for adaptation to fluconazole. 

Table of Contents

Table of Contents

Abstract.................................................................................................................................................5 Introduction...........................................................................................................................................7 Methods................................................................................................................................................11

C. albicans strains, media and experimental evolution...............................................................................11

Microbroth dilution assay........................................................................................................................12

Growth rate and analysis .........................................................................................................................12

C. elegans strains and media....................................................................................................................12

Seeding plates for liquid virulence assay and lineage expansion assay.........................................................13

Population synchronization for liquid virulence and lineage expansion assays.............................................13

Liquid virulence assay..............................................................................................................................14

Lineage expansion assay..........................................................................................................................14

Statistical analysis...................................................................................................................................15

Results ...................................................................................................................................................15

Evolved diploid and tetraploids have varied resistance to caspofungin.........................................................15

Resistance to caspofungin does not lead to decreased growth rate in the absence of antifungal .....................18

Evolved diploids are less resistant to fluconazole than ancestral C. albicans..................................................19

There is not a trade-off between caspofungin resistance and virulence in C. albicans.....................................22

Discussion ...............................................................................................................................................25 References................................................................................................................................................28 

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Microbiology
Keyword	virulence growth rate Candida albicans tradeoffs antifungal resistance
Committee Chair / Thesis Advisor	Hickman, Meleah, Emory University
Committee Members	McBride, Shonna, Emory University Morran, Levi, Emory University

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