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Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

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Poster number: 06<br />

Impact of non-fermentative growth on the C. albicans cell<br />

wall and dynamic responses to osmotic stress<br />

Iuliana V. Ene, Alistair J. P. Brown<br />

Aberdeen Fungal Group, School of Medical Sciences, University of Aberdeen, Foresterhill,<br />

Aberdeen AB25 2ZD, UK<br />

<strong>Candida</strong> albicans displays considerable metabolic flexibility and robust stress<br />

responses in vivo. Both contribute to the virulence of this pathogen. C. albicans<br />

assimilates both fermentative and non-fermentative carbon sources in vivo, often<br />

occupying poor glucose niches in its mammalian host. We reasoned that changes<br />

in carbon source might influence stress adaptation, but stress responses are<br />

generally studied during growth on glucose.<br />

We found that the C. albicans cell wall is extremely dynamic and susceptible to<br />

variations in carbon source. Growth on lactate rather than glucose has a major<br />

impact on cell wall structure and flexibility. Although the relative proportions of<br />

chitin, -glucan and mannan are similar within the wall of lactate-grown cells, they<br />

display increased porosity and decreased cell wall biomass. TEM confirmed major<br />

differences in cell wall architecture, underlying the importance of the carbon source<br />

in the cell biology of this pathogen. This in turn influences the responses of this<br />

pathogen to stresses as these differences were reflected in the cell wall-related<br />

phenotypes. Lactate-grown cells displayed higher resistance to Congo Red and<br />

Calcofluor White and showed significantly increased resistance to various doses<br />

of osmotic stress. This change was independent of Hog1 and Mkc1, but correlated<br />

with large changes in cell volume following exposure to NaCl. Growth on lactate<br />

also increased resistance to anti<strong>fungal</strong>s such as Caspofungin, Tunicamycin and<br />

Amphotericin B, which is likely to have a major impact upon the behavior of C.<br />

albicans during infection.<br />

The impact of carbon source on stress and drug resistance was confirmed in other<br />

pathogenic <strong>Candida</strong> species and for other carbon sources, resulting in variations<br />

in resistance when compared to a glucose-grown control. Clearly carbon source<br />

strongly influences cell wall architecture and the resistance of C. albicans to certain<br />

stresses, which is likely to have a major impact on its in vivo behavior.<br />

We are grateful to the European Commission for funding the <strong>FINSysB</strong> Marie Curie Initial<br />

Training Network (PITN-GA-2008-214004).<br />

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