Low iron-induced small RNA BrrF regulates central metabolism and oxidative stress responses in Burkholderia cenocepacia

Regulatory small RNAs play an essential role in maintaining cell homeostasis in bacteria in response to environmental stresses such as iron starvation. Prokaryotes generally encode a large number of RNA regulators, yet their identification and characterisation is still in its infancy for most bacterial species. Burkholderia cenocepacia is an opportunistic pathogen with high innate antimicrobial resistance, which can cause the often fatal cepacia syndrome in individuals with cystic fibrosis. In this study we characterise a small RNA which is involved in the response to iron starvation, a condition that pathogenic bacteria are likely to encounter in the host. BrrF is a small RNA highly upregulated in Burkholderia cenocepacia under conditions of iron depletion and with a genome context consistent with Fur regulation. Its computationally predicted targets include iron-containing enzymes of the tricarboxylic acid (TCA) cycle such as aconitase and succinate dehydrogenase, as well as iron-containing enzymes responsible for the oxidative stress response, such as superoxide dismutase and catalase. Phenotypic and gene expression analysis of BrrF deletion and overexpression mutants show that the regulation of these genes is BrrF-dependent. Expression of acnA, fumA, sdhA and sdhC was downregulated during iron depletion in the wild type strain, but not in a BrrF deletion mutant. TCA cycle genes not predicted as target for BrrF were not affected in the same manner by iron depletion. Likewise, expression of sodB and katB was dowregulated during iron depletion in the wild type strain, but not in a BrrF deletion mutant. BrrF overexpression reduced aconitase and superoxide dismutase activities and increased sensitivity to hydrogen peroxide. All phenotypes and gene expression changes of the BrrF deletion mutant could be complemented by overexpressing BrrF in trans. Overall, BrrF acts as a regulator of central metabolism and oxidative stress response, possibly as an iron-sparing measure to maintain iron homeostasis under conditions of iron starvation.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:15

Enthalten in:

PloS one - 15(2020), 7 vom: 24., Seite e0236405

Sprache:

Englisch

Beteiligte Personen:

Sass, Andrea M [VerfasserIn]
Coenye, Tom [VerfasserIn]

Links:

Volltext

Themen:

Aconitate Hydratase
BBX060AN9V
Bacterial Proteins
Catalase
E1UOL152H7
EC 1.11.1.6
EC 1.15.1.1
EC 4.2.1.3
Hydrogen Peroxide
Iron
Journal Article
RNA, Small Untranslated
Research Support, Non-U.S. Gov't
Superoxide Dismutase

Anmerkungen:

Date Completed 24.09.2020

Date Revised 24.09.2020

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.1371/journal.pone.0236405

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM312780826