Candida albicans is an important opportunistic yeast causing infections in susceptible host, but in healthy conditions is an harmless commensal. The pathogenicity of C. albicans is associated to either genomic or phenotypic characteristics that enable it to rapidly adapt to changing environmental, external signals, and help it in colonizing the host. The cell-hyphal transition is an example of virulence switching of C. albicans that promote tissue invasion and evasion of the host immune system. To investigate the intra-species variability in the phenotypical changes and immunoreactivity of C. albicans, we analyzed the whole genome sequences of 2 clinical strains (YL1 and YQ2). Whole genome analysis showed an intriguing genomic plasticity, an extreme variability and divergence between strains. Indeed, over the high polymorphism, strain-specific gene losses, acquisition, and several miss-sense genes were found. The most polymorphic genes codify proteins related to the cell wall and hyphal formation, suggesting a continuous adaptation to adverse environments or stress conditions. Genomic data were confirmed by phenotypical characterization showing changes in virulence related traits. Furthermore the fungal isolates were evaluated for their susceptibility and killing to microglia cells, and phagosome maturation in the BV2 microglia cells, used as an in vitro infection model. Although comparable in their susceptibility to phagocytosis by BV2 cells, these strains showed striking differences in term of intracellular survival. The YL1 isolate, in contrast to YQ2, resisted indeed to intracellular killing and eventually replicated inside the microglia. Moreover, we found a significantly lower percentage of YL1-containing acidic phagosomes, as compared to those observed in the YQ2-infected BV2 cells. These data suggest that YL1 may impair bactericidal activities of the microglia by inhibiting phagosome maturation. The increased virulence of YL1 shown in in vitro model appears to correlate with a different genetic makeup of this strain, particularly in genes involved in the pathogenesis of C. albicans. Our observations demonstrate that the nature and genomic features of C. albicans isolates dictate their adaptation to host environment generating phenotypic variability, which will translate into differential processing by phagocytes. Overall these results provide significant insights regarding the link between host adaptation, pathogenesis and evolution.
|Citation:||Rizzetto L.; Di Paola M.; Colombari B.; De Filippo C.; Ardizzoni A.; Berná L.; Tocci N.; Lionetti P.; Blasi E.; Cavalieri D.; Peppoloni S (2015-09). C. albicans with different genomic background reveal diverse host adaptation and differential processing by phagocytes. In: 27th International Conference on Yeast Genetics and Molecular Biology, Levico Terme (TN), 6-12 September 2015: S218 (PS11-12). url: http://onlinelibrary.wiley.com/doi/10.1002/yea.3092/epdf handle: http://hdl.handle.net/10449/26486|
|Organization unit:||Computational Biology # CRI_2011-JAN2016|
|Authors:||Rizzetto L.; Di Paola M.; Colombari B.; De Filippo C.; Ardizzoni A.; Berná L.; Tocci N.; Lionetti P.; Blasi E.; Cavalieri D.; Peppoloni S|
|Title:||C. albicans with different genomic background reveal diverse host adaptation and differential processing by phagocytes|
|Scientific Disciplinary Area:||Settore BIO/19 - Microbiologia Generale|
|Keywords ENG:||C. albicans|
|Appears in Collections:||03 - Conference object|