A periplasmic cinched protein is required for siderophore secretion and virulence of Mycobacterium tuberculosis.

TitleA periplasmic cinched protein is required for siderophore secretion and virulence of Mycobacterium tuberculosis.
Publication TypeJournal Article
Year of Publication2022
AuthorsZhang L, Kent JE, Whitaker M, Young DC, Herrmann D, Aleshin AE, Ko Y-H, Cingolani G, Saad JS, D Moody B, Marassi FM, Ehrt S, Niederweis M
JournalNat Commun
Volume13
Issue1
Pagination2255
Date Published2022 Apr 26
ISSN2041-1723
KeywordsAnimals, Iron, Mice, Mycobacterium tuberculosis, Siderophores, Tuberculosis, Virulence
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.

DOI10.1038/s41467-022-29873-6
Alternate JournalNat Commun
PubMed ID35474308
PubMed Central IDPMC9042941
Grant ListR21 AI151239 / AI / NIAID NIH HHS / United States
R35 GM118186 / GM / NIGMS NIH HHS / United States
P30 CA013148 / CA / NCI NIH HHS / United States
R35 GM140733 / GM / NIGMS NIH HHS / United States
S10 OD023479 / OD / NIH HHS / United States
R01 AI165573 / AI / NIAID NIH HHS / United States
R01 AI049313 / AI / NIAID NIH HHS / United States
P30 CA056036 / CA / NCI NIH HHS / United States

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