Effect of Physical and Chemical Cues on Candida albicans Morphological Expression and Biofilm Formation

Abstract

Adherent microbial communities, known as biofilms, are a major contributing factor in the incidence of healthcare-associated infections (HCAIs). HCAIs are responsible for annually causing 100,000 deaths and medical expenses estimated to be $35-45 billion. Physical and chemical surface modification techniques are thought to be critical in the fight against biofilm formation within medical settings. Nanoscale structural features have been found to have significant effects on bacterial adhesion and biofilm formation, but their effects on fungal pathogens are less explored. This thesis systematically explores the effect of surface topography in the form of nano and microscale polymeric fibers (~0.4-1.2 µm in diameter) on biofilm formation and virulence of a common HCAI-causing fungal pathogen, Candida albicans. We show that both C. albicans attachment density and differentiation to its virulent phenotype significantly vary with fiber diameter and spacing on polymeric fiber-coated surfaces. We further show that high throughput and high content techniques, such as Raman spectroscopy, can be used to track environmental and physical effects on the organism's resulting morphology and associated virulence. Findings from this thesis will inform the design of antifouling surfaces including implantable medical devices. In a prototypical example, we demonstrate the use of fiber coating to modulate C. albicans attachment on polyurethane, silicone, and latex catheters.