Metal ion transport and regulation in Mycobacterium tuberculosis

被引:50
作者
Agranoff, D [1 ]
Krishna, S [1 ]
机构
[1] St George Hosp, Sch Med, Dept Cellular & Mol Sci Infect Dis, London SW17 0RE, England
来源
FRONTIERS IN BIOSCIENCE-LANDMARK | 2004年 / 9卷
关键词
Mycobacterium tuberculosis; metal ion; transporter; siderophore; NRAMP; manganese; iron; review;
D O I
10.2741/1454
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The regulation of metal ion concentrations is central to the physiology of the interaction between pathogenic bacteria and their hosts. Apart from the NRAMP orthologue, MntH, metal ion transporters in Mycobacterium tuberculosis have not been studied. Mn, the physiological substrate of MntH in other bacteria, may play an important role as a structural and redox-active cofactor in a wide range of metabolic processes. Fe, Cu and Zn play structural and catalytic roles in metalloenzymes involved in oxidative stress responses. Fe and Mg are required for growth in macrophages. Genomic analyses reveal 28 sequences encoding a broad repertoire of putative metal ion transporters ( or transporter subunits), representing 24% of all transporters in this organism. These comprise 8 families of secondary active transporters and 3 families of primary active transporters, including 12 'P' type ATPases. Potential metal ion specificities include K+, Na+, Cu2+, Cd2+, Zn2+, Mn2+, Mg2+, Ca2+, Co2+, Ni2+, Fe2+/(3+), Hg2+, AsO2- and AsO42-. 17 of these transporters are also encoded as complete open reading frames in Mycobacterium leprae, suggesting a role in intracellular survival. Iron transcriptionally regulates a diverse set of genes via the iron-dependent DNA-binding proteins, Fur and IdeR. Changes in Fe and Mg concentrations signal entry into the intracellular compartment and potentially trigger upregulation of virulence determinants. The plethora of putative transport systems encoded by the M. tuberculosis genome contrasts strikingly with the paucity of experimental data on these systems. The detailed analysis of the temporal pattern of M. tuberculosis transporter gene expression during infection will provide important insights into the basic biology of intracellular parasitism and may help to shape novel therapeutic strategies.
引用
收藏
页码:2996 / 3006
页数:11
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