Iron-binding compounds of Mycobacterium avium, M. intracellulare, M. scrofulaceum, and mycobactin-dependent M. paratuberculosis and M. avium

Abstract

Fifty-three strains of M. avium and related species all produced one or more exochelins, the extracellular iron-binding compounds of the mycobacteria, when grown iron deficiently. Only those strains which could grow without the addition of mycobactin (i.e., mycobactin independent) produced mycobactin, the intracellular iron-binding compound of the mycobacteria. Exochelins varied from 20 to 2,000 ,ug per g of cell dry weight; mycobactins were between 1 and 10 mg per g of cell dry weight. M. paratuberculosis (13 strains) and 13 strains of M. avium, both species dependent upon mycobactin for growth, failed to produce spectrophotometrically detectable amounts of mycobactin (<0.2 ,ug per g of cell dry weight), although mycobactin could be recognized in one strain of M. avium grown with an additional supply of salicylate and examined by a radiolabeling technique. On repeated subculture three of the mycobactin-dependent strains of M. avium, but none of those of M. paratuberculosis, lost their mycobactin dependence and on reexamination were found to produce their own mycobactin at 0.3 mg per g of cell dry weight. It is concluded that mycobactin biosynthesis is probably strongly repressed in the mycobactin-dependent strains rather than being a genetic deletion. The exochelins, when examined by high-pressure thin-layer chromatography were revealed as being multiples of similar compounds, with up to 20 individual iron-binding compounds being recognizable with some strains. It is argued that the exochelins represent the single most important means of iron acquisition in mycobacteria growing in vitro and in vivo, and their elaboration by the fastidious M. paratuberculosis and related species explains how these organisms are able to grow in vivo in the absence of an external supply of mycobactin. 1138 on July 6, 2020 by guest

Identification of genes involved in the sequestration of iron in mycobacteria: the ferric exochelin biosynthetic and uptake pathways

“…However, exochelin was detected when the strain contained the complementing plasmids. Ratledge had demonstrated that mycobactin was not a precursor of exochelin (Barclay and Ratledge, 1983). Since the absence of exochelin does not block the synthesis of mycobactin, this confirms that exochelin is not a precursor of mycobactin and supports the hypothesis that the two siderophores have independent biosynthetic pathways.…”

“…However, the absence of mycobactins, even in the presence of exochelins, leaves some mycobacterial species unable to sequester iron outside the host. This is demonstrated by the necessity to supplement cultures of Mycobacterium paratubercuiosis, a strain that is unable to produce mycobactin, with either mycobactin or high levels of iron (Barclay and Ratledge. 1983).…”

Exochelin-mediated Iron Acquisition by the Leprosy Bacillus, Mycobacterium leprae

“…tuberculosis and M . avium (Stephenson & Ratledge, 1980;Barclay & Ratledge, 1983). The exochelins from M .…”

“…As little unchelated iron exists within the host, invading bacteria must obtain their iron from circulating iron-containing proteins, such as transferrin or lactoferrin, or from the iron-storage protein ferritin. Like many other bacteria, mycobacteria synthesize low molecular mass siderophores, termed exochelins, which can remove iron from these molecules (Macham et al, 1975) and thus provide a means for iron acquisition in mycobacteria growing both in vitro and in vivo (Barclay & Ratledge, 1983). Exochelins are of unknown structure but are probably pentapeptides with N-Ehydroxyornithines providing part or all of the chelating centre (A. J. M. Messenger, unpublished work (Macham et al, 1975;Messenger et al, 1986;Stephenson & Ratledge, 1980), it is impossible to assess the production of such compounds by M .…”

Iron uptake mechanisms of pathogenic bacteria

“…Examples of siderophore-mediated iron uptake systems have also been reported for Grampositive and acid fast bacterial species. The mycobacteria synthesise two types of iron-binding compound, exochelins and mycobactins [191][192][193]. The secreted water soluble exochelins solubilise iron and transport it to the cell; their structures have not been elucidated hut they may contain N-hydroxyornithine as the chelating moiety [194].…”