TY - JOUR
T1 - The genes that encode the gonococcal transferrin binding proteins, TbpB and TbpA, are differentially regulated by MisR under iron-replete and iron-depleted conditions
AU - Kandler, Justin L.
AU - Acevedo, Rosuany Vélez
AU - Dickinson, Mary Kathryne
AU - Cash, Devin R.
AU - Shafer, William M.
AU - Cornelissen, Cynthia Nau
N1 - Funding Information:
Funding for this work was provided to C.N.C. by Public Health Service grants R01 AI047141, R01 AI065555, R01 AI084400, and U19 AI31496 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. R.V.A. was supported by a diversity supplement to R01 AI047141. D.R.C. was supported by fellowship grant F30 AI112199 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. Additional support was provided to W.M.S. by Public Health Service grants U19 AI 113170, R37 AI21150, and U19 AI31496 all from the National Institute of Allergy and Infectious Diseases, National Institutes of Health and a VA Merit Award (510 1BX000112-07) from the Biomedical Laboratory Research and Development Service of the Department of Veterans Affairs. W.M.S. was also supported by a Senior Research Career Award from the Biomedical Laboratory Research and Development Service of the Department of Veterans Affairs. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. The authors thank Abena Watson-Siriboe and Virginia Stringer for excellent technical assistance. They also acknowledge the participation of two summer interns, Tiffany Wang and Kathryn Hebert, in the execution of the studies described in this report.
Publisher Copyright:
© 2016 John Wiley & Sons Ltd
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84988487372&partnerID=8YFLogxK
U2 - 10.1111/mmi.13450
DO - 10.1111/mmi.13450
M3 - Article
C2 - 27353397
AN - SCOPUS:84988487372
VL - 102
SP - 137
EP - 151
JO - Molecular Microbiology
JF - Molecular Microbiology
SN - 0950-382X
IS - 1
ER -