Understanding Biofilm Formation in Co-Cultures of Candida Albicans and Candida Glabrata
Abstract
Candida spp. are commensal opportunistic fungal pathogens that often colonize
and infect mucosal surfaces of the human body. Candida, along with other microbes in
the microbiota, generally grow as biofilms in a polymicrobial environment. Due to the
nature of cellular growth in a biofilm (such as production of a protective extracellular
matrix) and the recalcitrance of biofilms, infections involving biofilms are very difficult
to treat with antibiotics and perpetuate the cycle of infection. The two most commonly
isolated Candida spp. from Candida infections are Candida albicans and Candida
glabrata, and the presence of both of these species results in increased patient
inflammation and overall biofilm formation. In this work, we investigate the interspecies
interactions between C. albicans (Ca) and C. glabrata (Cg) in co-culture through
understanding biofilm formation, transcriptomic analysis, and the involvement of the
quorum-sensing molecule farnesol in biofilm formation. We report that biofilm formation
in co-culture populations of Ca and Cg is dependent on the relative starting concentrations
of each species, with the highest biofilm formation in a ratio of Ca:Cg 1:3. Confocal
microscopy analysis revealed increased biofilm heterogeneity and Ca hyphae length in co
culture biofilm compared to mono-culture biofilms. Several genes involved in Ca adhesion
(HWP1 and ALS3) were up-regulated in Ca:Cg 1:3 co-culture biofilms and there was also
an increase in resistance to the antifungal drug caspofungin in co-culture biofilms. Next,
we utilized transcriptomic analysis to further understand Ca:Cg interspecies interactions
within co-culture biofilms. We found that, in co-culture biofilms, lipid and cell wall
biosynthesis genes were significantly down-regulated and perturbed in both Ca and Cg,
and it was demonstrated that cell wall lipid content is increased in co-culture biofilms in
C. albicans via confocal microscopy. Finally, we investigated the relationship and
mechanisms of farnesol with C. glabrata cultures and also the impact of farnesol on co
culture biofilm formation. Results show possible Cg sequestration of farnesol and that
there are other factors likely at play during co-culture biofilm formation that leads to
increased biofilm formation, especially in the highest biofilm former Ca:Cg 1:3.
Citation
Olson, Michelle Lynn (2018). Understanding Biofilm Formation in Co-Cultures of Candida Albicans and Candida Glabrata. Doctoral dissertation, Texas A & M University. Available electronically from https : / /hdl .handle .net /1969 .1 /174409.