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

Wareham, LK and Begg, R and Jesse, HE and Van Beilen, JWA and Ali, S and Svistunenko, DA and McLean, S and Hellingwerf, KJ and Sanguinetti, G and Poole, RK (2016) 'Carbon Monoxide Gas Is Not Inert, but Global, in Its Consequences for Bacterial Gene Expression, Iron Acquisition, and Antibiotic Resistance.' Antioxidants & Redox Signaling, 24 (17). pp. 1013-1028. ISSN 1523-0864

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Aims: 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. Results: 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) offers little protection from antibiotics, a ruthenium CORM is a potent adjuvant of antibiotic activity. Innovation: This is the first detailed exploration of global bacterial responses to CO, revealing unexpected targets with implications for employing CORMs therapeutically. Conclusion: This work reveals the complexity of bacterial responses to CO and provides a basis for understanding the impacts of CO from CORMs, heme oxygenase activity, or environmental sources.

Item Type: Article
Uncontrolled Keywords: Escherichia coli; Carbon Monoxide; Iron; Amino Acids; Escherichia coli Proteins; Transcription Factors; Siderophores; Anti-Bacterial Agents; Microbial Sensitivity Tests; Drug Resistance, Microbial; Gene Expression Regulation, Bacterial; Protein Processing, Post-Translational; Aerobiosis; Anaerobiosis; Phosphorylation; Genes, Bacterial; Metabolic Networks and Pathways; Transcriptome
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 08 Jul 2016 08:00
Last Modified: 06 Jan 2022 13:39

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