TY - JOUR
T1 - A new role for Zinc limitation in bacterial pathogenicity
T2 - Modulation of α-hemolysin from uropathogenic Escherichia coli
AU - Velasco, Elsa
AU - Wang, Suning
AU - Sanet, Marianna
AU - Fernández-Vázquez, Jorge
AU - Jové, Daniel
AU - Glaría, Estibaliz
AU - Valledor, Annabel F.
AU - O'Halloran, Thomas V.
AU - Balsalobre, Carlos
N1 - Funding Information:
This work was supported by the Spanish Ministry of Economy and Competitiveness (grant AGL2013-45339-R, CB) (grant SAF2014-57856, A.F.V.), the Catalonian government (grant 2017SGR499, CB), the US National Institutes of Health (grants R01 GM038784, TVO). E.G. received a fellowship from the UB (APIF). We thank Dr. Cristina Madrid (Universitat de Barcelona) and Dr. Sandy Siepka (Northwestern University) for critical reading of the manuscript and fruitful discussions. We thank Northwestern University - the Keck Biophysics Facility for providing the Typhoon 9400 imager to scan the EMSA gels.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-018-24964-1
DO - 10.1038/s41598-018-24964-1
M3 - Article
C2 - 29695842
AN - SCOPUS:85045986303
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 6535
ER -