The Human Innate Immune Protein Calprotectin Elicits a Multimetal Starvation Response in Pseudomonas aeruginosa
Name
Spectrum.00519-21.pdf
Description
Published version
Size
1.83 MB
Format
Adobe PDF
Checksum (MD5)
f2de1a9945e865a01e936b3e3dc0a46c
Author(s)
Nelson, Cassandra E
Huang, Weiliang
Zygiel, Emily M
Nolan, Elizabeth M
Kane, Maureen A
Oglesby, Amanda G
Date Issued
2021
Journal
Microbiology Spectrum
Publisher
American Society for Microbiology
Citation
Nelson, Cassandra E, Huang, Weiliang, Zygiel, Emily M, Nolan, Elizabeth M, Kane, Maureen A et al. 2021. "The Human Innate Immune Protein Calprotectin Elicits a Multimetal Starvation Response in Pseudomonas aeruginosa." Microbiology Spectrum, 9 (2).
Version
Final published version
Abstract
To combat infections, the mammalian host limits availability of essential transition metals such as iron (Fe), zinc (Zn), and manganese (Mn) in a strategy termed “nutritional immunity.” The innate immune protein calprotectin (CP) contributes to nutritional immunity by sequestering these metals to exert antimicrobial activity against a broad range of microbial pathogens. One such pathogen is Pseudomonas aeruginosa, which causes opportunistic infections in vulnerable populations, including individuals with cystic fibrosis. CP was previously shown to withhold Fe(II) and Zn(II) from P. aeruginosa and induce Fe and Zn starvation responses in this pathogen. In this work, we performed quantitative, label-free proteomics to further elucidate how CP impacts metal homeostasis pathways in P. aeruginosa. We report that CP induces an incomplete Fe starvation response, as many Fe-containing proteins that are repressed by Fe limitation are not affected by CP treatment. The Zn starvation response elicited by CP seems to be more complete than the Fe starvation response and includes increases in Zn transporters and Zn-independent proteins. CP also induces the expression of membrane-modifying proteins, and metal depletion studies indicate this response results from the sequestration of multiple metals. Moreover, the increased expression of membrane-modifying enzymes upon CP treatment correlates with increased tolerance to polymyxin B. Thus, the response of P. aeruginosa to CP treatment includes both single- and multimetal starvation responses and includes many factors related to virulence potential, broadening our understanding of this pathogen’s interaction with the host.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1128/SPECTRUM.00519-21
