Metabolism and pH modulation in Candida spp. biofilms

Hyphal morphogenesis is critical for proper biofilm development, since mutants unable to form hyphae fail to produce robust biofilms (Ramsdale et al., Mol Cell Biol 2008; Klassert et al., Med Microbiol Immunol, 2014). Mature biofilms differ from planktonic growth in their limited diffusion of nutrients, oxygen and water and their resistance to antimicrobial agents and host immune responses. Moreover, Candida biofilm growth is linked to activation of the tricarboxylic acid (TCA) cycle and amino acid metabolism, conditions that promote modulation of environmental pH and hyphal morphogenesis by this organism (Kraidlova et al., Eukaryot Cell, 2011; Hernday et al., Mol Microbiol 2013). Other relevant to host niches alternative carbon sources, such as lactate and galactose, promote biofilm adherence, biomass and cellular dispersion (Gutbier et al., Am J Physiol Lung Cell Mol Physiol, 2015).

Thus, the objective of this project is to test if pH modulation and the metabolic state of the cells play role in biofilm formation, growth and dispersal. The proposed approach is to develop a methodology to monitor pH changes during biofilm growth and to test the requirement of nutrient utilization in this process. The successful completion of the proposed research will contribute to a missing component in our knowledge about metabolic and pH adaptation by C. albicans.

HFI Figure 3

The role of environmental neutralization in Candida spp. biofilm formation and virulence. The fungal pathogen C. albicans forms thick biofilms, consisting of yeast and hyphal cells encased in extracellular matrix (A). Mature biofilms are characterized by limited diffusion of nutrients, oxygen and water and their resistance to antimicrobial agents, and host immune responses. Our goal is to test if pH modulation contributes to biofilm formation and dispersal. Currently, we are developing microscopy-based methods for pH measurement within C. albicans biofilms (B).