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PLoS Pathog. 2015 Jul 6;11(7):e1005026. doi: 10.1371/journal.ppat.1005026. eCollection 2015 Jul.

Calprotectin Increases the Activity of the SaeRS Two Component System and Murine Mortality during Staphylococcus aureus Infections.

Author information

1
Indiana University School of Medicine-Northwest, Gary, Indiana, United States of America.
2
Institute of Immunology, University of Muenster, Muenster, Germany.
3
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
4
Department of Biochemistry and Chemistry, and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, United States of America.

Abstract

Calprotectin, the most abundant cytoplasmic protein in neutrophils, suppresses the growth of Staphylococcus aureus by sequestering the nutrient metal ions Zn and Mn. Here we show that calprotectin can also enhance the activity of the SaeRS two component system (TCS), a signaling system essential for production of over 20 virulence factors in S. aureus. The activity of the SaeRS TCS is repressed by certain divalent ions found in blood or neutrophil granules; however, the Zn bound-form of calprotectin relieves this repression. During staphylococcal encounter with murine neutrophils or staphylococcal infection of the murine peritoneal cavity, calprotectin increases the activity of the SaeRS TCS as well as the production of proinflammatory cytokines such as IL-1β and TNF-α, resulting in higher murine mortality. These results suggest that, under certain conditions, calprotectin can be exploited by S. aureus to increase bacterial virulence and host mortality.

PMID:
26147796
PMCID:
PMC4492782
DOI:
10.1371/journal.ppat.1005026
[Indexed for MEDLINE]
Free PMC Article

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