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Chapter 21 : Iron Metabolism in the Tubercle Bacillus and Other Mycobacteria

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Iron Metabolism in the Tubercle Bacillus and Other Mycobacteria, Page 1 of 2

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Abstract:

The mechanism of iron acquisition by mycobacteria, and by the tubercle bacillus in particular, is one of the central issues concerning the pathogenicity of this group of bacteria. This chapter describes the key components of the iron acquisition system, how they interlink in the sequestration of iron from the host sources of iron, and how the iron is then made available to the bacterial cell for its own purposes. Mycobactins have been isolated from and most other mycobacteria, both pathogens and nonpathogens alike. The only exceptions would appear to be some (but not necessarily all) strains of , , , , and . Two different types of ferritins involved in iron storage have been identified, the heme-containing bacterioferritins and the heme-free ferritins. In contrast to the genes of bacterial iron acquisition systems, which are upregulated under low-iron conditions, the genes encoding iron storage proteins appear to be upregulated under high-iron conditions. Interestingly, the first mycobacterial bacterioferritins were identified during the characterization of immunodominant and highly expressed mycobacterial proteins in the early 1990s. When a person becomes infected with the tubercle bacillus or, indeed, other bacteria, one of the earliest defense mechanisms put into operation by the infected host is the withholding of iron from the invading bacteria by the transfer of all free iron into transferrin or lactoferrin, both of which deliberately have spare iron-binding capacity for this very purpose. This means that iron is automatically in limiting supply to the bacteria also.

Citation: Quadri L, Ratledge C. 2005. Iron Metabolism in the Tubercle Bacillus and Other Mycobacteria, p 341-357. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch21

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Figures

Image of Figure 1.
Figure 1.

Structures of mycobactin and carboxymycobactin T from . The siderophores differ only in the nature of the R side chain. The side chain usually has a double bond at C-2 and a length of 17 to 20 carbons in mycobactin T ( ) or 2 to 9 carbons followed by a carboxylic group (or its methyl ester form) in carboxymycobactin T ( ). The atoms involved in iron binding are indicated by asterisks.

Citation: Quadri L, Ratledge C. 2005. Iron Metabolism in the Tubercle Bacillus and Other Mycobacteria, p 341-357. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch21
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Image of Figure 2.
Figure 2.

Diagram showing the suggested route of uptake of iron into via the carboxymycobactin route.

Citation: Quadri L, Ratledge C. 2005. Iron Metabolism in the Tubercle Bacillus and Other Mycobacteria, p 341-357. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch21
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Image of Figure 3.
Figure 3.

(Top) Structure of exochelin MS from Reproduced with permission from reference 64. © The Biochemical Society. (Bottom) Structure of exochelin MN from Reprinted from reference 63. © 1995, with permission from Elsevier.

Citation: Quadri L, Ratledge C. 2005. Iron Metabolism in the Tubercle Bacillus and Other Mycobacteria, p 341-357. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch21
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Image of Figure 4.
Figure 4.

Diagram showing the suggested route of uptake of iron into via the exochelin-mediated route.

Citation: Quadri L, Ratledge C. 2005. Iron Metabolism in the Tubercle Bacillus and Other Mycobacteria, p 341-357. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch21
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Image of Figure 5.
Figure 5.

Organization of gene clusters encoding the core of the biosynthetic machinery involved in the production of siderophores. (A) Gene clusters involved in the production of the aryl-capped peptide-polyketide mycobactin and carboxymycobactin siderophores in various species. (B) Gene clusters involved in the production of the peptide siderophore exochelin MS. Mt, ; Mb, ; Ms, ; Ma, ; Map, subsp. ; Mm, See the text for details of gene functions.

Citation: Quadri L, Ratledge C. 2005. Iron Metabolism in the Tubercle Bacillus and Other Mycobacteria, p 341-357. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch21
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Image of Figure 6.
Figure 6.

Differences in organization of predicted functional domains in the nonribosomal peptide synthetases MbtB and MbtE of various species. Species abbreviations are the same as in Fig. 5 . (A) Domain organization of MbtB homologs. The thioesterase domain in Mt and Mb is replaced by a separate thioesterase subunit in Ma, Map, Ms, and Mm. (B) Domain organization of MbtE homologs. The Ma and Map homologs appear to have an additional adenylation domain. The Map genome sequence corresponding to the MbtE coding region is frameshifted. Since the final annotation of the genome is not finished, it remains to be determined whether the frameshift is a sequencing error. Domain abbreviations: ArCP, aryl carrier protein domain; PCP, peptidyl carrier domain; Cy, cyclization domain; C, condensation domain; A, adenylation domain; T, thioesterase domain. The scale indicates the number of amino acids.

Citation: Quadri L, Ratledge C. 2005. Iron Metabolism in the Tubercle Bacillus and Other Mycobacteria, p 341-357. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch21
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