A reevaluation of iron binding by Mycobactin J

Courtney F. McQueen, John Taylor Groves

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Abstract: The complex stability constant (log β110) and the free iron concentration (pM) are used to compare the relative strength of iron binding by siderophores. Direct measurements of these thermodynamic parameters are often not possible for siderophores due to very large log β110 values ranging from 30 to 50. Instead, siderophore iron(III)-binding constants are determined by competitive experiments with other strong chelators with known values, such as EDTA. Iron(III) binding constants of water-insoluble siderophores, such as the mycobactins produced by the mycobacterium family, have never been directly measured. Since mycobactins contain two hydroxamic acid binding motifs, their log β110 values have been assumed to be comparable to those of other hydroxamate-based siderophores like desferrioxamine B, at ~ 30. However, exochelin MN, another mycobacterial siderophore that contains two hydroxamic acid moieties, has a log β110 of 39.1 and a pM of 31.1, which makes it among the strongest siderophores known. We have found that mycobactin J, the amphiphilic siderophore of Mycobacterium paratuberculosis, can remove iron(III) from TrenCAM (log β110 = 43.6) within 1 min in methanol. This surprising result indicates that log β110 for mycobactin J is ~ 43 and the ligand exchange kinetics in methanol is fast. The results imply that mycobactins are capable of removing iron quickly from very strongly binding siderophores in a cellular milieu. We propose a model mechanism for iron acquisition by pathogenic mycobacteria in vivo. This model explains how the host iron captured by siderophores can be returned to the invading pathogen even in the absence of active uptake mechanisms.

Original languageEnglish (US)
Pages (from-to)995-1007
Number of pages13
JournalJournal of Biological Inorganic Chemistry
Volume23
Issue number7
DOIs
StatePublished - Oct 1 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Inorganic Chemistry

Keywords

  • Bacterial microvesicles
  • Carboxymycobactin
  • Exochelin
  • Iron acquisition

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