A new role for Zinc limitation in bacterial pathogenicity: modulation of α-hemolysin from uropathogenic Escherichia coli
Abstract Metal limitation is a common situation during infection and can have profound effects on the pathogen’s success. In this report, we examine the role of zinc limitation in the expression of a virulence factor in uropathogenic Escherichia coli. The pyelonephritis isolate J96 carries two hlyCA...
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oai:doaj.org-article:a174d76b47b34380a2431c2c2639eec82021-12-02T15:08:39ZA new role for Zinc limitation in bacterial pathogenicity: modulation of α-hemolysin from uropathogenic Escherichia coli10.1038/s41598-018-24964-12045-2322https://doaj.org/article/a174d76b47b34380a2431c2c2639eec82018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24964-1https://doaj.org/toc/2045-2322Abstract Metal limitation is a common situation during infection and can have profound effects on the pathogen’s success. In this report, we examine the role of zinc limitation in the expression of a virulence factor in uropathogenic Escherichia coli. The pyelonephritis isolate J96 carries two hlyCABD operons that encode the RTX toxin α-hemolysin. While the coding regions of both operons are largely conserved, the upstream sequences, including the promoters, are unrelated. We show here that the two hlyCABD operons are differently regulated. The hly II operon is efficiently silenced in the presence of zinc and highly expressed when zinc is limited. In contrast, the hly I operon does not respond to zinc limitation. Genetic studies reveal that zinc-responsive regulation of the hly II operon is controlled by the Zur metalloregulatory protein. A Zur binding site was identified in the promoter sequence of the hly II operon, and we observe direct binding of Zur to this promoter region. Moreover, we find that Zur regulation of the hly II operon modulates the ability of E. coli J96 to induce a cytotoxic response in host cell lines in culture. Our report constitutes the first description of the involvement of the zinc-sensing protein Zur in directly modulating the expression of a virulence factor in bacteria.Elsa VelascoSuning WangMarianna SanetJorge Fernández-VázquezDaniel JovéEstibaliz GlaríaAnnabel F. ValledorThomas V. O’HalloranCarlos BalsalobreNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) |
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Medicine R Science Q Elsa Velasco Suning Wang Marianna Sanet Jorge Fernández-Vázquez Daniel Jové Estibaliz Glaría Annabel F. Valledor Thomas V. O’Halloran Carlos Balsalobre A new role for Zinc limitation in bacterial pathogenicity: modulation of α-hemolysin from uropathogenic Escherichia coli |
description |
Abstract Metal limitation is a common situation during infection and can have profound effects on the pathogen’s success. In this report, we examine the role of zinc limitation in the expression of a virulence factor in uropathogenic Escherichia coli. The pyelonephritis isolate J96 carries two hlyCABD operons that encode the RTX toxin α-hemolysin. While the coding regions of both operons are largely conserved, the upstream sequences, including the promoters, are unrelated. We show here that the two hlyCABD operons are differently regulated. The hly II operon is efficiently silenced in the presence of zinc and highly expressed when zinc is limited. In contrast, the hly I operon does not respond to zinc limitation. Genetic studies reveal that zinc-responsive regulation of the hly II operon is controlled by the Zur metalloregulatory protein. A Zur binding site was identified in the promoter sequence of the hly II operon, and we observe direct binding of Zur to this promoter region. Moreover, we find that Zur regulation of the hly II operon modulates the ability of E. coli J96 to induce a cytotoxic response in host cell lines in culture. Our report constitutes the first description of the involvement of the zinc-sensing protein Zur in directly modulating the expression of a virulence factor in bacteria. |
format |
article |
author |
Elsa Velasco Suning Wang Marianna Sanet Jorge Fernández-Vázquez Daniel Jové Estibaliz Glaría Annabel F. Valledor Thomas V. O’Halloran Carlos Balsalobre |
author_facet |
Elsa Velasco Suning Wang Marianna Sanet Jorge Fernández-Vázquez Daniel Jové Estibaliz Glaría Annabel F. Valledor Thomas V. O’Halloran Carlos Balsalobre |
author_sort |
Elsa Velasco |
title |
A new role for Zinc limitation in bacterial pathogenicity: modulation of α-hemolysin from uropathogenic Escherichia coli |
title_short |
A new role for Zinc limitation in bacterial pathogenicity: modulation of α-hemolysin from uropathogenic Escherichia coli |
title_full |
A new role for Zinc limitation in bacterial pathogenicity: modulation of α-hemolysin from uropathogenic Escherichia coli |
title_fullStr |
A new role for Zinc limitation in bacterial pathogenicity: modulation of α-hemolysin from uropathogenic Escherichia coli |
title_full_unstemmed |
A new role for Zinc limitation in bacterial pathogenicity: modulation of α-hemolysin from uropathogenic Escherichia coli |
title_sort |
new role for zinc limitation in bacterial pathogenicity: modulation of α-hemolysin from uropathogenic escherichia coli |
publisher |
Nature Portfolio |
publishDate |
2018 |
url |
https://doaj.org/article/a174d76b47b34380a2431c2c2639eec8 |
work_keys_str_mv |
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