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Journal of Bacteriology, June 2007, p. 4046-4052, Vol. 189, No. 11
0021-9193/07/$08.00+0     doi:10.1128/JB.00026-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Iron-Dependent RNA-Binding Activity of Mycobacterium tuberculosis Aconitase{triangledown}

Sharmistha Banerjee,1,2 Ashok Kumar Nandyala,1 Podili Raviprasad,1,{dagger} Niyaz Ahmed,1 and Seyed E. Hasnain1,2,3*

Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, 500076, India,1 University of Hyderabad, Hyderabad 500046, India,2 Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560012, India3

Received 5 January 2007/ Accepted 15 March 2007

Cellular iron levels are closely monitored by iron regulatory and sensor proteins of Mycobacterium tuberculosis for survival inside macrophages. One such class of proteins systematically studied in eukaryotes and reported in a few prokaryotes are the iron-responsive proteins (IRPs). These IRPs bind to iron-responsive elements (IREs) present at untranslated regions (UTRs) of mRNAs and are responsible for posttranscriptional regulation of the expression of proteins involved in iron homeostasis. Amino acid sequence analysis of M. tuberculosis aconitase (Acn), a tricarboxylic acid (TCA) cycle enzyme, showed the presence of the conserved residues of the IRP class of proteins. We demonstrate that M. tuberculosis Acn is bifunctional. It is a monomeric protein that is enzymatically active in converting isocitrate to cis-aconitate at a broad pH range of 7 to 10 (optimum, pH 8). As evident from gel retardation assays, M. tuberculosis Acn also behaves like an IRP by binding to known mammalian IRE-like sequences and to predicted IRE-like sequences present at the 3' UTR of thioredoxin (trxC) and the 5' UTR of the iron-dependent repressor and activator (ideR) of M. tuberculosis. M. tuberculosis Acn when reactivated with Fe2+ functions as a TCA cycle enzyme, but upon iron depletion by a specific iron chelator, it behaves like an IRP, binding to the selected IREs in vitro. Since iron is required for the Acn activity and inhibits the RNA-binding activity of Acn, the two activities of M. tuberculosis Acn are mutually exclusive. Our results demonstrate the bifunctional nature of M. tuberculosis Acn, pointing to its likely role in iron homeostasis.

* Corresponding author. Mailing address: Office of the Vice Chancellor, University of Hyderabad, P.O. Central University, Gachibowli, Hyderabad, 500046, India. Phone: 91 40 23010121. Fax: 91 40 23011090. E-mail: seh{at}ouhyd.ernet.in

{triangledown} Published ahead of print on 23 March 2007.

{dagger} Present address: Molecular Biology Unit, National Institute of Nutrition, Jamia Osmania, Hyderabad 500007, India.

Journal of Bacteriology, June 2007, p. 4046-4052, Vol. 189, No. 11
0021-9193/07/$08.00+0     doi:10.1128/JB.00026-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • van Schaik, E. J., Tom, M., Woods, D. E. (2009). Burkholderia pseudomallei Isocitrate Lyase Is a Persistence Factor in Pulmonary Melioidosis: Implications for the Development of Isocitrate Lyase Inhibitors as Novel Antimicrobials. Infect. Immun. 77: 4275-4283 [Abstract] [Full Text]  


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