Show simple item record

dc.contributor.authorWilson, Tyree
dc.contributor.authorMouriño, Susana
dc.contributor.authorWilks, Angela
dc.date.accessioned2021-03-29T18:19:08Z
dc.date.available2021-03-29T18:19:08Z
dc.date.issued2021-01-09
dc.identifier.urihttp://hdl.handle.net/10713/15051
dc.description.abstractPseudomonas aeruginosa is an opportunistic pathogen requiring iron for its survival and virulence. P. aeruginosa can acquire iron from heme via the nonredundant heme assimilation system and Pseudomonas heme uptake (Phu) systems. Heme transported by either the heme assimilation system or Phu system is sequestered by the cytoplasmic protein PhuS. Furthermore, PhuS has been shown to specifically transfer heme to the iron-regulated heme oxygenase HemO. As the PhuS homolog ShuS from Shigella dysenteriae was observed to bind DNA as a function of its heme status, we sought to further determine if PhuS, in addition to its role in regulating heme flux through HemO, functions as a DNA-binding protein. Herein, through a combination of chromatin immunoprecipitation-PCR, EMSA, and fluorescence anisotropy, we show that apo-PhuS but not holo-PhuS binds upstream of the tandem iron-responsive sRNAs prrF1,F2. Previous studies have shown the PrrF sRNAs are required for sparing iron for essential proteins during iron starvation. Furthermore, under certain conditions, a heme-dependent read through of the prrF1 terminator yields the longer PrrH transcript. Quantitative PCR analysis of P. aeruginosa WT and ΔphuS strains shows that loss of PhuS abrogates the hemedependent regulation of PrrF and PrrH levels. Taken together, our data show that PhuS, in addition to its role in extracellular heme metabolism, also functions as a transcriptional regulator by modulating PrrF and PrrH levels in response to heme. This dual function of PhuS is central to integrating extracellular heme utilization into the PrrF/PrrH sRNA regulatory network that is critical for P. aeruginosa adaptation and virulence within the host. © 2021 The Authors.en_US
dc.description.urihttps://doi.org/10.1016/j.jbc.2021.100275en_US
dc.language.isoenen_US
dc.publisherElsevier Inc.en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.rightsCopyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.en_US
dc.subjecthemeen_US
dc.subjectiron-metabolismen_US
dc.subjectDNA-bindingen_US
dc.subjectbacterial pathogenesisen_US
dc.subjectsRNAen_US
dc.subject.meshPseudomonas aeruginosaen_US
dc.titleThe heme binding protein PhuS transcriptionally regulates the Pseudomonas aeruginosa tandem sRNA prrF1,F2 locusen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.jbc.2021.100275
dc.identifier.pmid33428928
dc.source.beginpage100275
dc.source.endpage
dc.source.countryUnited States


Files in this item

Thumbnail
Name:
Publisher version

This item appears in the following Collection(s)

Show simple item record