The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages

J J De Voss; Kerry-Lee Rutter; B G Schroeder; H Su; Y Zhu; C E III Barry

doi:10.1073/pnas.97.3.1252

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The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages

Journal article

Peer reviewed

The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages

J J De Voss, Kerry-Lee Rutter, B G Schroeder, H Su, Y Zhu and C E III Barry

Proceedings of the National Academy of Sciences of the United States of America, Vol.97(3), pp.1252-1257

2000

DOI: https://doi.org/10.1073/pnas.97.3.1252

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Abstract

Mycobacterium tuberculosis is an important pathogen of mammals that relies on 2-hydroxyphenyloxazoline-containing siderophore molecules called mycobactins for the acquisition of iron in the restrictive environment of the mammalian macrophage. These compounds have been proposed to be biosynthesized through the action of a cluster of genes that include both nonribosomal peptide synthase and polyketide synthase components. One of these genes encodes a protein, MbtB, that putatively couples activated salicylic acid with serine or threonine and then cyclizes this precursor to the phenyloxazoline ring system. We have used gene replacement through homologous recombination to delete the mbtB gene and replace this with a hygromycin-resistance cassette in the virulent strain of M. tuberculosis H37Rv. The resulting mutant is restricted for growth in iron-limited media but grows normally in iron-replete media. Analysis of siderophore production by this organism revealed that the biosynthesis of all salicylate-derived siderophores was interrupted. The mutant was found to be impaired for growth in macrophage-like THP-1 cells, suggesting that siderophore production is required for virulence of M. tuberculosis. These results provide conclusive evidence linking this genetic locus to siderophore production.

Details

Title: The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages
Authors: J J De Voss (Author) - University of Queensland
Kerry-Lee Rutter (Author) - University of Queensland
B G Schroeder (Author) - National Institute of Allergy and Infectious Disease, United States
H Su (Author) - National Institute of Allergy and Infectious Disease, United States
Y Zhu (Author) - National Institute of Allergy and Infectious Disease, United States
C E III Barry (Author) - National Institute of Allergy and Infectious Disease, United States
Publication details: Proceedings of the National Academy of Sciences of the United States of America, Vol.97(3), pp.1252-1257
Publisher: National Academy of Sciences
Date published: 2000
DOI: 10.1073/pnas.97.3.1252
ISSN: 0027-8424
Organisation Unit: School of Tertiary Access - Legacy; School of Education and Tertiary Access; University of the Sunshine Coast, Queensland
Language: English
Record Identifier: 99450124602621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Biochemistry & Molecular Biology

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