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

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