Interactions between haemoglobin and Candida albicans and the dynamics of biofilm formation on airway management devices

This thesis is formed of two distinct research projects: An investigation into polymicrobial biofilm formation on tracheal tubing; and the characterisation of an interaction between methaemoglobin, and the human fungal pathogen Candida albicans. In place of a traditional introduction, Chapter 1 is book chapter, published in a Springer series on fungal biofilm formation. (1) This review provides the sufficient context for chapters 2 and 3. Chapter 2 is systematic review published in Wiley MicrobiologyOpen. (2) Chapter 3 documents research conducted in collaboration with ICU Medical Inc as a series of research reports submitted to ICU Medical Inc throughout the project. Chapter 4 will provide the context required for Chapters 5 and 6, which are written in traditional chapter format. Chapter 7 is a broad discussion of the complete thesis. Throughout this thesis, and within Chapter 6 particularly, the terms “tolerance” and “resistance” are used in the context of susceptibility to antimicrobial therapies. In the current field of mycology, different laboratories apply different definitions for each of these terms which can cause confusion. Here we define “tolerance” as the inefficacy of an antimicrobial therapy due to a non-hereditable phenotypic trait (e.g the production of an extracellular matrix physically shielding normally susceptible planktonic cells). We define “resistance” as a hereditable trait driven by selection or mobile genetic elements (e.g the production of beta-lactamases to degrade beta-lactam containing antibiotics). A single bibliography combines references from all chapters.