Document Type
Article
Publication Date
4-26-2022
Abstract
Iron is essential for growth of Mycobacterium tuberculosis, the causative agent of tuberculosis. To acquire iron from the host, M. tuberculosis uses the siderophores called mycobactins and carboxymycobactins. Here, we show that the rv0455c gene is essential for M. tuberculosis to grow in low-iron medium and that secretion of both mycobactins and carboxymycobactins is drastically reduced in the rv0455c deletion mutant. Both water-soluble and membrane-anchored Rv0455c are functional in siderophore secretion, supporting an intracellular role. Lack of Rv0455c results in siderophore toxicity, a phenotype observed for other siderophore secretion mutants, and severely impairs replication of M. tuberculosis in mice, demonstrating the importance of Rv0455c and siderophore secretion during disease. The crystal structure of a Rv0455c homolog reveals a novel protein fold consisting of a helical bundle with a 'cinch' formed by an essential intramolecular disulfide bond. These findings advance our understanding of the distinct M. tuberculosis siderophore secretion system.
Recommended Citation
Zhang, Lei; Kent, James E; Whitaker, Meredith; Young, David C; Herrmann, Dominik; Aleshin, Alexander E; Ko, Ying-Hui; Cingolani, Gino; Saad, Jamil S; Moody, D Branch; Marassi, Francesca M; Ehrt, Sabine; and Niederweis, Michael, "A periplasmic cinched protein is required for siderophore secretion and virulence of Mycobacterium tuberculosis." (2022). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 215.
https://jdc.jefferson.edu/bmpfp/215
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
35474308
Language
English
Comments
This article is the author’s final published version in Nature Communications, Volume 13, Issue 1, April 2022, Article number 2255.
The published version is available at https://doi.org/10.1038/s41467-022-29873-6. Copyright © Zhang et al.