DNA supercoiling differences in bacteria result from disparate DNA gyrase activation by polyamines

• Published in: PLoS genetics Vol. 16; no. 10; p. e1009085
• Main Authors: Duprey, Alexandre, Groisman, Eduardo A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.10.2020; Public Library of Science (PLoS)
• Subjects: Adenosine triphosphate; Amino acids; Antibacterial agents; Bacteria; Biology and Life Sciences; Deoxyribonucleic acid; DNA; DNA Gyrase - drug effects; DNA Gyrase - genetics; DNA topoisomerase; DNA Topoisomerases, Type I - drug effects; DNA Topoisomerases, Type I - genetics; DNA, Superhelical - drug effects; DNA, Superhelical - genetics; E coli; Enzymes; Escherichia coli - drug effects; Escherichia coli - enzymology; Escherichia coli - genetics; Genes; Genetic aspects; Magnesium; Magnesium - pharmacology; Medical research; Medicine and Health Sciences; Metabolites; Pathogenesis; Physiological aspects; Polyamines; Proteins; Putrescine; Putrescine - pharmacology; Research and Analysis Methods; Salmonella; Salmonella typhimurium - drug effects; Salmonella typhimurium - enzymology; Salmonella typhimurium - genetics; Signal transduction; Spermidine; Spermidine - biosynthesis; Supercoiling; United States; United States > US
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1009085

DNA supercoiling is essential for all living cells because it controls all processes involving DNA. In bacteria, global DNA supercoiling results from the opposing activities of topoisomerase I, which relaxes DNA, and DNA gyrase, which compacts DNA. These enzymes are widely conserved, sharing >91% amino acid identity between the closely related species Escherichia coli and Salmonella enterica serovar Typhimurium. Why, then, do E. coli and Salmonella exhibit different DNA supercoiling when experiencing the same conditions? We now report that this surprising difference reflects disparate activation of their DNA gyrases by the polyamine spermidine and its precursor putrescine. In vitro, Salmonella DNA gyrase activity was sensitive to changes in putrescine concentration within the physiological range, whereas activity of the E. coli enzyme was not. In vivo, putrescine activated the Salmonella DNA gyrase and spermidine the E. coli enzyme. High extracellular Mg2+ decreased DNA supercoiling exclusively in Salmonella by reducing the putrescine concentration. Our results establish the basis for the differences in global DNA supercoiling between E. coli and Salmonella, define a signal transduction pathway regulating DNA supercoiling, and identify potential targets for antibacterial agents.