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Differential roles for the Co^sup 2+^/Ni^sup 2+^ transporting ATPases, CtpD and CtpJ, in Mycobacterium tuberculosis virulence

The genome of Mycobacterium tuberculosis encodes two paralogous P1B4-ATPases, CtpD (Rv1469) and CtpJ (Rv3743). Both proteins showed ATPase activation by ... and ..., and both appear to be required for metal efflux from the cell. However, using a combination of biochemical and genetic studies we foun...

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Bibliographic Details
Published in:Molecular microbiology 2014-01, Vol.91 (1), p.185
Main Authors: Raimunda, Daniel, Long, Jarukit E, Padilla-Benavides, Teresita, Sassetti, Christopher M, Argüello, José M
Format: Article
Language:English
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Summary:The genome of Mycobacterium tuberculosis encodes two paralogous P1B4-ATPases, CtpD (Rv1469) and CtpJ (Rv3743). Both proteins showed ATPase activation by ... and ..., and both appear to be required for metal efflux from the cell. However, using a combination of biochemical and genetic studies we found that these proteins play non-redundant roles in virulence and metal efflux. CtpJ expression is induced by ... and this protein possesses a relatively high turnover rate. A ctpJ deletion mutant accumulated ..., indicating that this ATPase controls cytoplasmic metal levels. In contrast, CtpD expression is induced by redox stressors and this protein displays a relatively low turnover rate. A ctpD mutant failed to accumulate metal, suggesting an alternative cellular function. ctpD is cotranscribed with two thioredoxin genes trxA (Rv1470), trxB (Rv1471), and an enoyl-coA hydratase (Rv1472), indicating a possible role for CtpD in the metallation of these redox-active proteins. Supporting this, in vitro metal binding assays showed that TrxA binds ... and ... Mutation of ctpD, but not ctpJ, reduced bacterial fitness in the mouse lung, suggesting that redox maintenance, but not ... accumulation, is important for growth in vivo. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0950-382X
1365-2958