Aggregation and Filamentation of Candida albicans in Response to Pressure Asymmetry.
Abstract: The human
opportunistic pathogen Candida albicans colonizes biotic and abiotic surfaces, grows
within tissue, and proliferates in blood. C. albicans alters its morphology, growing as
yeast or elongated filamentous hyphae, and its colony structure, forming dispersed
suspensions, colonies or biofilms, to exploit its surroundings and to spread to
additional areas. Understanding the ... read moreresponses and their environmental triggers grants
valuable insight into pathogenesis. In a phenotype reminiscent of the invasive
filamentation of human tissue during candidiasis, C. albicans filaments in response to
growth in contact with a semi-solid agar matrix. The transmembrane protein Dfi1p is
required for this response. To better understand the role of Dfi1p, the cues that
promote Dfi1p-dependent filamentation were identified and analyzed. Different aspects of
the physical environment, such as pressure and viscosity, were independently varied and
tested to identify the physical features of the environment that trigger Dfi1p-dependent
filamentation. As a result of this testing, the asymmetric application of pressure due
to depletion attraction was found to cause Dfi1p-dependent filamentation. This finding
implies that Dfi1p senses contact when there is an imbalance of compressive pressure
around the cell. Thus, for the first time asymmetric pressure has been identified as a
physical mechanism to which C. albicans can respond. Further studies of Dfi1p
interaction with the cell wall and of the contribution of different portions of the
putative extracellular domain revealed a complex and intimate association with the cell
wall. Physiologically, depletion attraction is notable as the mechanism of rouleaux
formation, the aggregation of red blood cells into linear stacks. C. albicans cells also
initially aggregate in blood, plasma, or serum due to depletion attraction. This
behavior may impact pathogenesis during disseminated candidiasis and is the first time
that aggregation of a microbial pathogen in blood has been shown to be driven by
depletion attraction in blood. The findings here indicate that asymmetric pressure
promotes hyphal morphogenesis and that depletion attraction causes rapid, reversible
aggregation of C. albicans in blood.
Thesis (Ph.D.)--Tufts University, 2014.
Submitted to the Dept. of Molecular Microbiology.
Advisors: Carol Kumamoto, and Linden Hu.
Committee: Abraham Sonenshein, Andrew Wright, and Ariel Amir.
Keywords: Microbiology, Biology, and Molecular biology.read less