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Chapter 23 : Pathogenic Mycobacteria
Authors:
G. Marcela Rodriguez1,
Issar Smith1
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Affiliations:
1: TB Center, Public Health Research Institute at the International Center for Public Health, 225 Warren St., Newark, NJ 07103–3535
Content Type: Monograph
Publication Year:
2004
Category: Bacterial Pathogenesis; Clinical Microbiology
Book DOI:
10.1128/9781555816544
Chapter DOI:
10.1128/9781555816544.ch23
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Pathogenic Mycobacteria, Page 1 of 2
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Abstract:
This chapter focuses on the information presently available about iron metabolism and its regulation in pathogenic mycobacteria; this information is derived mainly from experiments conducted with Mycobacterium tuberculosis. Mycobactins produced by different species vary mainly in the alkyl substitutions of the hydroxy acid and in the length of the acyl molecule, which varies between 10 and 21 carbons. The proteins encoded by the mbt cluster show significant homology to proteins involved in the biosynthesis of other structurally related siderophores such as yersiniabactin from Yersinia pestis and pyochelin from Pseudomonas aeruginosa. Disruption of the mbtB gene in M. tuberculosis results in loss of production of both mycobactin and carboxymycobactin, indicating a direct link between the mbt genes and siderophore synthesis. Carboxymycobactin is probably responsible for sequestering iron from transferrin in the phagosome, since normal release of iron from transferrin triggered by the acidic pH of the early endosome is reduced as a result of mycobacterium inhibition of phagosome acidification. A common characteristic of components of iron acquisition systems in prokaryotes and in higher organisms is that they are expressed only under conditions of iron limitation. Iron-dependent regulator (IdeR) is responsible for the differential expression of one-third of the M. tuberculosis genes whose expression is affected by iron availability.
Citation:
Rodriguez G, Smith I.
2004.
Pathogenic Mycobacteria,
p 360-371.
In
Crosa J, Mey A, Payne S,
Iron Transport in Bacteria.
ASM Press, Washington, DC.
doi: 10.1128/9781555816544.ch23
Figures
Pathogenic Mycobacteria
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Citation:
Rodriguez G, Smith I.
2004.
Pathogenic Mycobacteria,
p 360-371.
In
Crosa J, Mey A, Payne S,
Iron Transport in Bacteria.
ASM Press, Washington, DC.
doi: 10.1128/9781555816544.ch23
/content/10.1128/9781555816544.chap23.fig23-1
FIGURE 1
Core structure of mycobactin and carboxymycobactin. Substituents: (a) H can be found in carboxymycobactins and in some mycobactins, whereas in others the group is a CH3. (b) Both of these substitutions can be found in mycobactins and in carboxymycobactins. (c) CH3 is found in the M. tuberculosis carboxymycobactin and in mycobactins from M. fortuitum, M. thermoresistibile, M. avium, M. smegmatis, and M. tuberculosis; C2H5 is found in carboxymycobactin of M. avium and in mycobactins from M. avium, M. phlei, and M. terrae; C15–18 is found in mycobactin from M. marinum; and C3H9 is found in mycobactin from M. paratuberculosis. (d) Both of these substitutions can be found in mycobactins and carboxymycobactins. (e) A long alkyl substitution, C10–21, is found in mycobactins, whereas a shorter form, C2–9, is found in carboxymycobactin. Molecules carrying the methyl ester have been found in M. tuberculosis and M. avium.
10.1128/9781555816544/fig23-1_thmb.gif
10.1128/9781555816544/fig23-1.gif
FIGURE 1
Core structure of mycobactin and carboxymycobactin. Substituents: (a) H can be found in carboxymycobactins and in some mycobactins, whereas in others the group is a CH3. (b) Both of these substitutions can be found in mycobactins and in carboxymycobactins. (c) CH3 is found in the M. tuberculosis carboxymycobactin and in mycobactins from M. fortuitum, M. thermoresistibile, M. avium, M. smegmatis, and M. tuberculosis; C2H5 is found in carboxymycobactin of M. avium and in mycobactins from M. avium, M. phlei, and M. terrae; C15–18 is found in mycobactin from M. marinum; and C3H9 is found in mycobactin from M. paratuberculosis. (d) Both of these substitutions can be found in mycobactins and carboxymycobactins. (e) A long alkyl substitution, C10–21, is found in mycobactins, whereas a shorter form, C2–9, is found in carboxymycobactin. Molecules carrying the methyl ester have been found in M. tuberculosis and M. avium.
Citation:
Rodriguez G, Smith I.
2004.
Pathogenic Mycobacteria,
p 360-371.
In
Crosa J, Mey A, Payne S,
Iron Transport in Bacteria.
ASM Press, Washington, DC.
doi: 10.1128/9781555816544.ch23
/content/10.1128/9781555816544.chap23.fig23-2
FIGURE 2
Proposed scheme for the biosynthesis of mycobactin and carboxymycobactin from M. tuberculosis: See the text for a detailed description of the predicted reactions. Confirmation of this model awaits the characterization of the proposed enzymatic activity in vitro for the known enzymes as well as the identification of the acyltransferase(s), the nature of its specificity, and the precise substrate used for these reactions.
10.1128/9781555816544/fig23-2_thmb.gif
10.1128/9781555816544/fig23-2.gif
FIGURE 2
Proposed scheme for the biosynthesis of mycobactin and carboxymycobactin from M. tuberculosis: See the text for a detailed description of the predicted reactions. Confirmation of this model awaits the characterization of the proposed enzymatic activity in vitro for the known enzymes as well as the identification of the acyltransferase(s), the nature of its specificity, and the precise substrate used for these reactions.
Citation:
Rodriguez G, Smith I.
2004.
Pathogenic Mycobacteria,
p 360-371.
In
Crosa J, Mey A, Payne S,
Iron Transport in Bacteria.
ASM Press, Washington, DC.
doi: 10.1128/9781555816544.ch23
/content/10.1128/9781555816544.chap23.fig23-3
FIGURE 3
Genes regulated by the iron-dependent regulator IdeR. The genes shown have been characterized as direct targets of IdeR regulation by DNA binding and DNase footprinting analyses; all are from M. tuberculosis except for fxbA, which is from M. smegmatis. The transcriptional start sites in the promoters, indicated by +1, were mapped by primer extension analysis. The boxes indicate IdeR binding sites, defined as protected regions in footprinting analysis. In some cases there is more than one iron box in this sequence. The black boxes indicate IdeR binding sites in the promoters of genes that are repressed by iron and IdeR. The striped boxes indicate the sites required for IdeR binding in the promoters of genes whose transcription is activated by iron and IdeR.
10.1128/9781555816544/fig23-3_thmb.gif
10.1128/9781555816544/fig23-3.gif
FIGURE 3
Genes regulated by the iron-dependent regulator IdeR. The genes shown have been characterized as direct targets of IdeR regulation by DNA binding and DNase footprinting analyses; all are from M. tuberculosis except for fxbA, which is from M. smegmatis. The transcriptional start sites in the promoters, indicated by +1, were mapped by primer extension analysis. The boxes indicate IdeR binding sites, defined as protected regions in footprinting analysis. In some cases there is more than one iron box in this sequence. The black boxes indicate IdeR binding sites in the promoters of genes that are repressed by iron and IdeR. The striped boxes indicate the sites required for IdeR binding in the promoters of genes whose transcription is activated by iron and IdeR.
Citation:
Rodriguez G, Smith I.
2004.
Pathogenic Mycobacteria,
p 360-371.
In
Crosa J, Mey A, Payne S,
Iron Transport in Bacteria.
ASM Press, Washington, DC.
doi: 10.1128/9781555816544.ch23
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