Document Type
Article
Version Deposited
Published Version
Publication Date
11-13-2024
Publication Title
mBio Bacteriology
DOI
10.1128/mbio.02310-24
Abstract
Iron (Fe) is a trace nutrient required by nearly all organisms. As a result of the demand for Fe and the toxicity of non-chelated cytosolic ionic Fe, regulatory systems have evolved to tightly balance Fe acquisition and usage while limiting overload. In most bacteria, including the mammalian pathogen Staphylococcus aureus, the ferric uptake regulator (Fur) is the primary transcriptional regulator controlling the transcription of genes that code for Fe uptake and utilization proteins. Fpa (formerly YlaN) was demonstrated to be essential in Bacillus subtilis unless excess Fe is added to the growth medium, suggesting a role in Fe homeostasis. Here, we demonstrate that Fpa is essential in S. aureus upon Fe deprivation. Null fur alleles bypassed the essentiality of Fpa. The absence of Fpa abolished the derepression of Fur-regulated genes during Fe limitation. Bioinformatic analyses suggest that fpa was recruited to Gram-positive bacteria and, once acquired, was maintained in the genome as it co-evolved with Fur. Consistent with a role for Fpa in alleviating Fur-dependent repression, Fpa and Fur interacted in vivo, and Fpa decreased the DNA-binding ability of Fur in vitro. Fpa bound Fe(II) in vitro using oxygen or nitrogen ligands with an association constant that is consistent with a physiological role in Fe homeostasis. These findings have led to a model wherein Fpa is an Fe(II) binding protein that influences Fur-dependent regulation through direct interaction.
Recommended Citation
Boyd JM, Ryan Kaler K, Esquilín-Lebrón K, Pall A, Campbell CJ, Foley ME, Rios-Delgado G, Mustor EM, Stephens TG, Bovermann H, Greco TM, Cristea IM, Carabetta VJ, Beavers WN, Bhattacharya D, Skaar EP, Shaw LN, Stemmler TL.2024.Fpa (YlaN) is an iron(II) binding protein that functions to relieve Fur-mediated repression of gene expression in Staphylococcus aureus. mBio15:e02310-24.https://doi.org/10.1128/mbio.02310-24
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Comments
Copyright © 2024 Boyd et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.