Journal Article

FZJ-2020-02463

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png HrrSA orchestrates a systemic response to heme and determines prioritization of terminal cytochrome oxidase expression

Keppel, M. ; Hünnefeld, M.FZJ* ; Filipchyk, A.FZJ* ; Viets, U.FZJ* ; Davoudi, C.-F. ; Krüger, A.FZJ* ; Mack, C.FZJ* ; Pfeifer, E. ; Polen, T.FZJ* ; Baumgart, M.FZJ* ; Bott, M.FZJ* ; Frunzke, J. (Corresponding author)FZJ*

2020
Information Retrieval Ltd.86606 London

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Please use a persistent id in citations: http://hdl.handle.net/2128/25261  doi:10.1093/nar/gkaa415

Abstract: Heme is a multifaceted molecule. While serving as a prosthetic group for many important proteins, elevated levels are toxic to cells. The complexity of this stimulus has shaped bacterial network evolution. However, only a small number of targets controlled by heme-responsive regulators have been described to date. Here, we performed chromatin affinity purification and sequencing to provide genome-wide insights into in vivo promoter occupancy of HrrA, the response regulator of the heme-regulated two-component system HrrSA of Corynebacterium glutamicum. Time-resolved profiling revealed dynamic binding of HrrA to more than 200 different genomic targets encoding proteins associated with heme biosynthesis, the respiratory chain, oxidative stress response and cell envelope remodeling. By repression of the extracytoplasmic function sigma factor sigC, which activates the cydABCD operon, HrrA prioritizes the expression of genes encoding the cytochrome bc1-aa3 supercomplex. This is also reflected by a significantly decreased activity of the cytochrome aa3 oxidase in the ΔhrrA mutant. Furthermore, our data reveal that HrrA also integrates the response to heme-induced oxidative stress by activating katA encoding the catalase. These data provide detailed insights in the systemic strategy that bacteria have evolved to respond to the versatile signaling molecule heme.

Note: Biotechnologie 1

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Contributing Institute(s):

1. Biotechnologie (IBG-1)

Research Program(s):

1. 581 - Biotechnology (POF3-581) (POF3-581)
2. DFG project 284242796 - Spezifität der Phosphatase-Aktivität und Interaktion Häm-abhängiger Zweikomponentensysteme in Corynebacterium glutamicum (284242796)

Appears in the scientific report 2020

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