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Nfu facilitates the maturation of iron‐sulfur proteins and participates in virulence in S taphylococcus aureus
Summary The acquisition and metabolism of iron ( Fe ) by the human pathogen S taphylococcus aureus is critical for disease progression. S . aureus requires Fe to synthesize inorganic cofactors called iron‐sulfur ( Fe‐S ) clusters, which are required for functional Fe‐S proteins. In this study we inv...
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Published in: | Molecular microbiology 2015-02, Vol.95 (3), p.383-409 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Summary
The acquisition and metabolism of iron (
Fe
) by the human pathogen
S
taphylococcus aureus
is critical for disease progression.
S
. aureus
requires
Fe
to synthesize inorganic cofactors called iron‐sulfur (
Fe‐S
) clusters, which are required for functional
Fe‐S
proteins. In this study we investigated the mechanisms utilized by
S
. aureus
to metabolize
Fe‐S
clusters. We identified that
S
. aureus
utilizes the Suf biosynthetic system to synthesize
Fe‐S
clusters and we provide genetic evidence suggesting that the
suf
U
and
suf
B
gene products are essential. Additional biochemical and genetic analyses identified
Nfu
as an
Fe‐S
cluster carrier, which aids in the maturation of
Fe‐S
proteins. We find that deletion of the
nfu
gene negatively impacts staphylococcal physiology and pathogenicity. A
nfu
mutant accumulates both increased intracellular non‐incorporated Fe and endogenous reactive oxygen species (
ROS
) resulting in
DNA
damage. In addition, a strain lacking
Nfu
is sensitive to exogenously supplied
ROS
and reactive nitrogen species. Congruous with
ex vivo
findings, a
nfu
mutant strain is more susceptible to oxidative killing by human polymorphonuclear leukocytes and displays decreased tissue colonization in a murine model of infection. We conclude that
Nfu
is necessary for staphylococcal pathogenesis and establish
Fe‐S
cluster metabolism as an attractive antimicrobial target. |
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ISSN: | 0950-382X 1365-2958 |
DOI: | 10.1111/mmi.12860 |