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Cell wall stress elicits a conserved response in Candida
albicans
Alice G. Sorgo, Clemens J. Heilmann, Sepehr Mohammady, Henk L.
Dekker, Stanley Brul, Chris de Koster, Leo J. de Koning and Frans M. Klis
Swammerdam Institute for Life Sciences, Universiteit van Amsterdam, Science Park 904,
1098 XH Amsterdam, The Netherlands
Both cell wall proteins and secreted proteins of C. albicans are critical for fitness,
virulence and adaptation to environmental challenges. We have recently shown that
fluconazole, an antifungal drug that affects ergosterol synthesis and increases
membrane fluidity, also causes cell wall stress as evidenced by decreased
resistance to wall-perturbing compounds and higher chitin levels in the wall (1). This
is accompanied by substantial changes in the wall proteome and secretome. We
found that the abundance of proteins mainly involved in wall biosynthesis and
integrity increased (Crh11, Pga4, Pir1, Phr1, Phr2, Sap9). However, the abundance
of hypha-associated proteins (Als3, Hwp1, Plb5) decreased in agreement with
reduced hyphal growth. Finally, fluconazole induced cell clustering. As membrane
fluidity also tends to increase at higher temperatures, we wanted to investigate
whether the response to thermal stress is similar to that of fluconazole and could
also result in cell wall stress. When C. albicans was cultured at 42°C, which resulted
in substantial growth inhibition, the cells showed indeed decreased resistance to
wall-perturbing agents, and chitin levels in the wall were elevated, both suggesting
cell wall stress. Likewise, the wall proteome response was similar to that of
fluconazole-treated cells, including increased incorporation levels of proteins
important for wall maintenance and integrity. Additionally, cell separation was
impaired, correlating with a severe reduction of the chitinases Cht2 and Cht3 and
the endoglucanase Eng1 in the medium. In summary, our data indicate that both
thermal stress and fluconazole-induced stress induce membrane stress, which
leads to cell wall stress and a conserved wall stress response.
References
(1) The effects of fluconazole on the secretome, the wall proteome and wall integrity of the clinical fungus
Candida albicans. Sorgo AG, Heilmann CJ, Dekker HL, Bekker M, Brul S, de Koster CG, de Koning LJ,
Klis FM. Eukaryot Cell. 2011. doi:10.1128/EC.05011-11.
We are grateful to the European Commission for funding the FINSysB Marie Curie Initial Training Network
(PITN-GA-2008-214004).
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