Differential roles for the Co2+/Ni2+ transporting ATPases, CtpD and CtpJ, in Mycobacterium tuberculosis virulence. Issue 1 (20th November 2013)

• Record Type: Journal Article
• Authors: Raimunda, Daniel; Long, Jarukit E.; Padilla‐Benavides, Teresita; Sassetti, Christopher M.; Argüello, José M.
• Is Part Of: Molecular microbiology. Volume 91:Issue 1(2014)
• Page Start: 185
• Page End: 197
• Publication Date: 2013-11-20
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12454
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>The genome of <italic>Mycobacterium tuberculosis</italic> encodes two paralogous P<sub>1</sub><sub>B</sub><sub>4</sub>‐ATPases, CtpD (<italic>Rv1469</italic>) and CtpJ (<italic>Rv3743</italic>). Both proteins showed ATPase activation by Co<sup>2+</sup> and Ni<sup>2+</sup>, 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 Co<sup>2+</sup> and this protein possesses a relatively high turnover rate. A <italic>ctpJ</italic> deletion mutant accumulated Co<sup>2+</sup>, 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 <italic>ctpD</italic> mutant failed to accumulate metal, suggesting an alternative cellular function. <italic>ctpD</italic> is cotranscribed with two thioredoxin genes <italic>trxA</italic> (<italic>Rv1470</italic>), <italic>trxB</italic> (<italic>Rv1471</italic>), and an enoyl‐coA hydratase (<italic>Rv1472</italic>), indicating a possible role for CtpD in the metallation of these redox‐active proteins. Supporting this, <italic>in vitro</italic> metal binding assays showed that TrxA binds Co<sup>2+</sup> and Ni<sup>2+</sup>. Mutation of <italic>ctpD</italic>, but not <italic>ctpJ</italic>, reduced bacterial fitness in the mouse lung, suggesting that redox maintenance, but not Co<sup>2+</sup> accumulation, is important for growth <italic>in vivo</italic>.</p> </abstract>