Neutrophil S100A8/A9 (calprotectin ) zinc chelation regulates Aspergillus fumigatus hyphal growth in vitro and in a murine model of corneal infection

Ref ID: 19593


HL Clark1*, Y Sun1, JP Latgé2, JA Calera3, E Pearlman1

Author address:

1Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, USA
2Laboratoire des Aspergillus, Institut Pasteur, Paris, France
3Departamento de Microbiologí­a y Genética, Universidad de Salamanca, Salamanca, Spain

Full conference title:

6th Advances Against Aspergillosis 2014


Zinc is required for many cellular processes that are essential for fungal growth and survival. S100A8
and S100A9 are proteins abundant in neutrophils which compete for free Zn2+, thereby limiting
fungal growth. We examined the role of neutrophil S100A8/A9 in killing wild-type Aspergillus
fumigatus and A. fumigatus strains with mutations in the transcription factor ZafA, zinc importers
ZrfA/ZrfB and ZrfC and secreted protein Aspf2, all of which comprise the A. fumigatus zinc uptake
system in zinc limiting environments.
The purpose of this study is to examine the role of neutrophil S100A8/A9 in control of A. fumigatus
growth in vivo and in vitro and to determine whether A. fumigatus zinc uptake allows for fungal
survival in the presence of S100A8/A9.
Wild-type or mutant strains of A. fumigatus were incubated with neutrophils from S100A9-/- and
control C57BL/6 mice in low (RPMI 1640) or high Zn2+ (RPMI + ZnSO4) media, and fungal growth
was quantified by total chitin. The role of S100A8/A9 was also examined in a well-established
murine model of corneal disease.
C57BL/6 neutrophils inhibited the growth of wild-type and all mutant strains of A. fumigatus in
low Zn2+, which was ablated in by adding exogenous Zn2+. In contrast to C57BL/6 neutrophils,
S100A9-/- neutrophils were unable to control the growth of wild-type, 916;ZrfA/B and 916;Aspf2 strains
in low Zn2+, but did limit the growth of 916;ZafA and 916;ZrfC strains. Growth of wild-type A. fumigatus
in the corneal stroma was significantly higher in S100A9-/- mice compared to C57BL/6 mice,
although there was no difference in neutrophil infiltration.
Neutrophil S100A8/A9 regulates growth of wild-type A. fumigatus in vivo and in vitro by competing
for available Zn2+. The susceptibility of 916;ZrfC and 916;ZafA mutants to killing by S100A9-/-
neutrophils suggests a role for additional mechanisms of zinc control by neutrophils and indicates
that ZafA and ZrfC are essential for A. fumigatus survival in the presence of neutrophils.

Abstract Number: 118

Conference Year: 2014

Link to conference website:

New link: NULL

Conference abstracts, posters & presentations

Showing 10 posts of 17225 posts found.
  • Title





Our sponsors