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HERO ID
5931291
Reference Type
Journal Article
Title
Multi-metal Restriction by Calprotectin Impacts De Novo Flavin Biosynthesis in Acinetobacter baumannii
Author(s)
Wang, J; Lonergan, ZR; Gonzalez-Gutierrez, G; Nairn, BL; Maxwell, CN; Zhang, Y; Andreini, C; Karty, JA; Chazin, WJ; Trinidad, JC; Skaar, EP; Giedroc, DP
Year
2019
Volume
26
Issue
5
Page Numbers
745-755.e7
Language
English
PMID
30905682
DOI
10.1016/j.chembiol.2019.02.011
Web of Science Id
WOS:000468134800016
Abstract
Calprotectin (CP) inhibits bacterial viability through extracellular chelation of transition metals. However, how CP influences general metabolism remains largely unexplored. We show here that CP restricts bioavailable Zn and Fe to the pathogen Acinetobacter baumannii, inducing an extensive multi-metal perturbation of cellular physiology. Proteomics reveals severe metal starvation, and a strain lacking the candidate ZnII metallochaperone ZigA possesses altered cellular abundance of multiple essential Zn-dependent enzymes and enzymes in de novo flavin biosynthesis. The ΔzigA strain exhibits decreased cellular flavin levels during metal starvation. Flavin mononucleotide provides regulation of this biosynthesis pathway, via a 3,4-dihydroxy-2-butanone 4-phosphate synthase (RibB) fusion protein, RibBX, and authentic RibB. We propose that RibBX ensures flavin sufficiency under CP-induced Fe limitation, allowing flavodoxins to substitute for Fe-ferredoxins as cell reductants. These studies elucidate adaptation to nutritional immunity and define an intersection between metallostasis and cellular metabolism in A. baumannii.
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