Impact of ROS-Induced Damage of TCA Cycle Enzymes on Metabolism and Virulence of Salmonella enterica serovar Typhimurium

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Title: Impact of ROS-Induced Damage of TCA Cycle Enzymes on Metabolism and Virulence of Salmonella enterica serovar Typhimurium
Authors: Noster, Janina
Persicke, Marcus
Chao, Tzu-Chiao
Krone, Lena
Heppner, Bianca
Hensel, Michael
Hansmeier, Nicole
ORCID of the author: https://orcid.org/0000-0001-6239-8614
https://orcid.org/0000-0002-8802-6605
https://orcid.org/0000-0001-8781-6958
https://orcid.org/0000-0001-6604-6253
Abstract: Salmonella enterica serovar Typhimurium (STM) is exposed to reactive oxygen species (ROS) originating from aerobic respiration, antibiotic treatment, and the oxidative burst occurring inside the Salmonella-containing vacuole (SCV) within host cells. ROS damage cellular compounds, thereby impairing bacterial viability and inducing cell death. Proteins containing iron–sulfur (Fe–S) clusters are particularly sensitive and become non-functional upon oxidation. Comprising five enzymes with Fe–S clusters, the TCA cycle is a pathway most sensitive toward ROS. To test the impact of ROS-mediated metabolic perturbations on bacterial physiology, we analyzed the proteomic and metabolic profile of STM deficient in both cytosolic superoxide dismutases (ΔsodAB). Incapable of detoxifying superoxide anions (SOA), endogenously generated SOA accumulate during growth. ΔsodAB showed reduced abundance of aconitases, leading to a metabolic profile similar to that of an aconitase-deficient strain (ΔacnAB). Furthermore, we determined a decreased expression of acnA in STM ΔsodAB. While intracellular proliferation in RAW264.7 macrophages and survival of methyl viologen treatment were not reduced for STM ΔacnAB, proteomic profiling revealed enhanced stress response. We conclude that ROS-mediated reduced expression and damage of aconitase does not impair bacterial viability or virulence, but might increase ROS amounts in STM, which reinforces the bactericidal effects of antibiotic treatment and immune responses of the host.
Citations: Front. Microbiol. 10:762, 2019
URL: https://repositorium.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-201907171818
Subject Keywords: metabolomics; oxidative stress; iron–sulfur cluster damage; aconitase; superoxide dismutase
Issue Date: 24-Apr-2019
License name: Attribution 4.0 International
License url: http://creativecommons.org/licenses/by/4.0/
Type of publication: Einzelbeitrag in einer wissenschaftlichen Zeitschrift [article]
Appears in Collections:FB05 - Hochschulschriften

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