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The genes that encode the gonococcal transferrin binding proteins, TbpB and TbpA, are differentially regulated by MisR under iron‐replete and iron‐depleted conditions
Author(s) -
Kandler Justin L.,
Acevedo Rosuany Vélez,
Dickinson Mary Kathryne,
Cash Devin R.,
Shafer William M.,
Cornelissen Cynthia Nau
Publication year - 2016
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13450
Subject(s) - biology , mutant , transferrin , gene , transferrin receptor , microbiology and biotechnology , genetics , biochemistry
Summary Neisseria gonorrhoeae produces two transferrin binding proteins, TbpA and TbpB, which together enable efficient iron transport from human transferrin. We demonstrate that expression of the tbp genes is controlled by MisR, a response regulator in the two‐component regulatory system that also includes the sensor kinase MisS. The tbp genes were up‐regulated in the misR mutant under iron‐replete conditions but were conversely down‐regulated in the misR mutant under iron‐depleted conditions. The misR mutant was capable of transferrin‐iron uptake at only 50% of wild‐type levels, consistent with decreased tbp expression. We demonstrate that phosphorylated MisR specifically binds to the tbpBA promoter and that MisR interacts with five regions upstream of the tbpB start codon. These analyses confirm that MisR directly regulates tbpBA expression. The MisR binding sites in the gonococcus are only partially conserved in Neisseria meningitidis , which may explain why tbpBA was not MisR‐regulated in previous studies using this related pathogen. This is the first report of a trans ‐acting protein factor other than Fur that can directly contribute to gonococcal tbpBA regulation.