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

Poster number: 36
Survival of Candida glabrata within phagocytes
Lydia Schild, Katja Seider, Pedro Miramón, Sascha Brunke and Bernhard
Hube
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product
Research and Infection Biology – Hans Knoell Institute (HKI), Jena, Germany
Candida glabrata is both a human commensal and a pathogenic fungus. Immune
evasion strategies likely play a key role during infection since C. glabrata elicits little
inflammation in mice. To investigate immune evasion as a pathogenic strategy, we
characterize the interaction of C. glabrata with human phagocytes such as
macrophages and neutrophils.
C. glabrata is able to survive and even replicate within human macrophages in vitro.
Low pro-inflammatory response to fungal infection and inhibition of macrophage
ROS production by C. glabrata support the view that this fungus can persist in
macrophages as an immune evasion strategy. Our data suggest that C. glabrata
modifies phagosome maturation, residing in a non-acidic phagosome. While the
inhibition of ROS production is affected by viability of fungal cells, inhibition of
phagosome maturation does not require metabolic activity of the fungus. Instead,
an UV-indestructible fungal attribute seems to be involved this process.
To elucidate which C. glabrata factors are responsible for modification of
phagosome maturation and persistence in phagocytes, we analyzed a set of
deletion mutants for survival in macrophages and identified 24 genes that are crucial
for intracellular survival of C. glabrata within macrophages. Phenotypic analyses of
these mutants point to an important role of cell wall integrity and stress resistance
for macrophage survival of C. glabrata. Furthermore, nutrient acquisition, in
particular iron uptake has been shown to play a role during intra-phagosomal
persistence.
Similar attributes seem to be important for resistance to neutrophils, as mutants
lacking genes with suggested functions in cell wall integrity and nutritional sensing
are attenuated in survival in both, neutrophils and macrophages.
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