Carbon Monoxide Gas Is Not Inert, but Global, in Its Consequences for Bacterial Gene Expression, Iron Acquisition, and Antibiotic Resistance.

Antioxidants & Redox Signaling
Lauren K WarehamRobert K Poole

Abstract

Carbon monoxide is a respiratory poison and gaseous signaling molecule. Although CO-releasing molecules (CORMs) deliver CO with temporal and spatial specificity in mammals, and are proven antimicrobial agents, we do not understand the modes of CO toxicity. Our aim was to explore the impact of CO gas per se, without intervention of CORMs, on bacterial physiology and gene expression. We used tightly controlled chemostat conditions and integrated transcriptomic datasets with statistical modeling to reveal the global effects of CO. CO is known to inhibit bacterial respiration, and we found expression of genes encoding energy-transducing pathways to be significantly affected via the global regulators, Fnr, Arc, and PdhR. Aerobically, ArcA-the response regulator-is transiently phosphorylated and pyruvate accumulates, mimicking anaerobiosis. Genes implicated in iron acquisition, and the metabolism of sulfur amino acids and arginine, are all perturbed. The global iron-related changes, confirmed by modulation of activity of the transcription factor Fur, may underlie enhanced siderophore excretion, diminished intracellular iron pools, and the sensitivity of CO-challenged bacteria to metal chelators. Although CO gas (unlike H2S and NO) of...Continue Reading

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Citations

Sep 8, 2018·Biochemical Society Transactions·Lauren K WarehamRobert K Poole
Jun 4, 2020·International Journal of Molecular Sciences·Habibu AliyuAnke Neumann
Mar 6, 2021·The Journal of Biological Chemistry·Michael S MedinaCedric P Owens
Oct 23, 2020·Chemical Reviews·Christopher P HopperBinghe Wang
May 13, 2021·MSystems·Katherine BaylyChris Greening
Jun 3, 2021·Antioxidants·Sofia S MendesLígia M Saraiva
Jul 3, 2021·Pharmaceutics·Alexandra-Cristina Munteanu, Valentina Uivarosi

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Datasets Mentioned

BETA
GSE50713

Methods Mentioned

BETA
electrophoresis
electron paramagnetic resonance
Assay

Software Mentioned

TFInfer
GeneSpring GX
GeneSpring
ArcA
EcoCyc

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