Candida Infection Biology – fungal armoury, battlefields ... - FINSysB
Candida Infection Biology – fungal armoury, battlefields ... - FINSysB
Candida Infection Biology – fungal armoury, battlefields ... - FINSysB
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Poster number: 17<br />
Dissecting the response of <strong>Candida</strong> albicans to the attack<br />
by neutrophils<br />
Pedro Miramón 1 , Iryna Bohovych 4 , Alistair J. P. Brown 4 , Oliver Kurzai 2,3 ,<br />
Bernhard Hube 1,3<br />
1 Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product<br />
Research and <strong>Infection</strong> <strong>Biology</strong> - Hans Knoell Institute (HKI), Jena, Germany; 2 Department of<br />
Fungal Septomics, Leibniz Institute for Natural Product Research and <strong>Infection</strong> <strong>Biology</strong> - Hans<br />
Knoell Institute (HKI), Jena, Germany; 3 Friedrich-Schiller Universität, Jena, Germany; 4 Aberdeen<br />
Fungal Group, Institute of Medical Sciences, University of Aberdeen, UK<br />
<strong>Candida</strong> albicans successfully colonises diverse niches in the human host without causing any<br />
harm thanks to a balance with the microflora and possibly due to a constant surveillance of<br />
patrolling immune cells. However, under certain conditions, this fungus is able to cause lifethreatening<br />
deep-seated infections. Although it is know that neutrophils are key players in<br />
controlling and eliminating C. albicans, it is unclear how C. albicans is killed by neutrophils and<br />
how the fungus counteracts these phagocytes.<br />
By means of single-cell expression profiling using GFP reporter strains, we characterised<br />
different responses of C. albicans to three main neutrophil-imposed stresses: nutrient starvation,<br />
oxidative stress and nitrosative stress.<br />
We observed that phagocytosed <strong>fungal</strong> cells responded to carbohydrate starvation by<br />
upregulating the glyoxylate cycle, but not the glycolytic pathway. Moreover, a mutant lacking a<br />
key gene of the glyoxylate cycle (icl1 ) exhibited decreased resistance in the presence of<br />
neutrophils.<br />
Next, we investigated the contribution of oxidative stress to killing by neutrophil. The catalase<br />
gene CTA1 was induced upon phagocytosis. However, the surface-associated superoxide<br />
dismutase gene SOD5 was induced in yeast cells even before phagocytosis took place,<br />
suggesting that C. albicans can sense and encounter an extracellular oxidative attack. In a<br />
similar fashion, the thioredoxin gene TRX1 was also upregulated upon extracellular contact with<br />
neutrophils. Strikingly, neither cta1 nor trx1 mutants exhibited decreased resistance to<br />
neutrophils, suggesting that they are not essential for normal resistance of C. albicans. However,<br />
sod5 was more sensitive to neutrophils, indicating that Sod5 is an important detoxifying enzyme<br />
to cope with neutrophil-generated oxidative stress. C. albicans also responded to nitrosative<br />
stress generated in the intracellular milieu and this response was essential for full resistance as<br />
a yhb1 mutant, defective in nitric oxide dioxygenase, exhibited decreased survival.<br />
In summary, our study provides evidence that C. albicans displays specific responses to<br />
overcome either extracellular or intracellular attack by neutrophils.<br />
We are grateful to the European Commission for funding the <strong>FINSysB</strong> Marie Curie Initial Training Network (PITN-GA-<br />
2008-214004).<br />
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