Rajagopalan, Malini, Ph.D.
Ph.D, 1986, The University of Delhi, India
Mycobacterium tuberculosis multiplication: Players and Pathways.
- Proliferation of Mycobacterium tuberculosis.
- Regulation of cell cycle of Mycobacterium tuberculosis.
Infections with Mycobacterium tuberculosis (Mtb) are responsible for active tuberculosis in 14 million people worldwide and tuberculosis continues to be a leading cause of death due to a single infectious agent. The deadly synergy of tuberculosis with HIV/AIDS combined with the worldwide spread of MDR- and XDR- tuberculosis emphasizes the need for new effective and faster acting TB drugs to provide shorter (and less toxic) therapy regimens. A hallmark of tuberculosis is latency/dormancy where the bacterium maintains low turnover rate without causing any disease. While it is known that the lipid-rich thick cell walls allow the pathogen to withstand the actions of antibiotics and antimicrobial peptides, the bacterial factors regulating the entry into and exit from dormancy are not completely understood. Thus, studies on pathways responsible for bacterial multiplication can provide critical insights into the survival mechanisms used by Mtb.
We have been studying the cell cycle of Mtb with a goal of identifying key players that can serve as potential drug targets. Over the past decade, we have uncovered several novel aspects of Mtb multiplication and identified some novel protein engaged in the process (see publications). Some of our current work involves evaluating the role of these proteins on survival of Mtb in macrophage and animal models. Other ongoing studies are focused on understanding the regulation of Mtb cell cycle using biochemical and genetic approaches.
Selected Papers and Abstracts:
- Plocinski P, Arora N, Sarva K, Blaszczyk E, Qin H, Das N, Plocinska R, Ziolkiewicz M, Dziadek J, Kiran M, Gorla P, Cross TA., Madiraju M, Rajagopalan,M. (2012) Mycobacterium tuberculosis CwsA interacts with CrgA and Wag31 and the CrgA-CwsA complex is involved in peptidoglycan synthesis and cell shape determination. J. Bacteriology 194:6398.
- Plocinska R., Purushotham G, Sarva K, Vadrevu SI, Pandeeti EV, Arora N, Plocinski P, Madiraju M, Rajagopalan M. (2012). Septal localization of Mycobacterium tuberculosis MtrB sensor kinsase promotes MtrA regulon expression. J. Biol. Chem. 287:23887-23899.
- Plocinski P, Ziolkiewicz M, Kiran M, Vadrevu SI, Nguyen HB, Hugonnet J, Veckerle C, Arthur M, Dziadek J, Cross TA, Madiraju M, Rajagopalan M. 2011. Characterization of CrgA, a New Partner of the Mycobacterium tuberculosis Peptidoglycan Polymerization Complexes. J. Bacteriology 193 (13): 3246-56.
- Estrella JL, Kan-Sutton C, Gong X, Rajagopalan M, Lewis DL, Hunter RL, Eissa NT, and Jagannath C. 2011. A novel in vitro human macrophage model to study the persistence of Mycobacterium tuberculosis using vitamin D3 and retinoic acid activated THP-1 macrophages. Frontiers in Microbiology 2(67): 1 – 16.
- Al Zayer M, Stankowska D, Dziedzic R, Sarva K, Madiraju MV, Rajagopalan M. 2011. Mycobacterium tuberculosis mtrA merodiploid strains with point mutations in the signal-receiving domain of MtrA exhibit growth defects in nutrient broth. Plasmid. 2011 May;65(3):210-8. Epub 2011 Feb 3.
- Maloney E, Lun S, Stankowska D, Guo H, Rajagoapalan M, Bishai WR, Madiraju MV. (2011) Alterations in phospholipid catabolism in Mycobacterium tuberculosis lysX mutant. Frontiers in Microbiology 2 (19) : 1 - 10
- Dziedzic R, Plocinski P, Ziolkiewicz M, Brzostek A, Moomey M, Vadrevu IS , Dziadek J, Rajagopalan, M. (2010) Mycobacterium tuberculosis ClpX interacts with FtsZ and interferes with FtsZ assembly. PlosOne 5(7): e11058.
- Rajagopalan M, Dziedzic R, Al Zayer M, Stankowska D, Ouimet MC, Bastedo DP, Marczynski GT, Madiraju MV. (2010) Mycobacterium tuberculosis origin of replication and the promoter for immunodominant secreted antigen 85B are the targets of MtrA, the essential response regulator. J Biol Chem. 285(21):15816-27. Epub 2010 Mar 11.
- Kiran M, Maloney M, Lofton H, Chauhan A, Jensen, Dziedzic R, Madiraju M, Rajagopalan M. (2009). Mycobacterium tuberculosis ftsZ expression and minimal promoter activity. Tuberculosis 89 (S1) S60-S64.
- Maloney E, Madiraju M, Rajagopalan M. (2009) Overproduction and purification of Mycobacterium tuberculosis ParA and ParB proteins. Tuberculosis 89 (S1) S65-S69.
- Kiran M, Chauhan A, Dziedzic R, Mukherje, S, Madiraju M. Rajagopalan M. (2009). Mycobacterium tuberculosis ftsH expression in response to stress and viability. Tuberculosis 89 (S1) S70-S73.
- Maloney E, Stankowska D, Zhang J, Fol M., Cheng QJ, Lun S, Bishai WR, Rajagopalan M, Chatterjee D, Madiraju MVV. (2009). The two-domain LysX protein is required for production of lysinylated phosphatidylglycerol and resistance to cationic antimicrobial peptides. PLoS Pathogens: 5 (7): e100534.
- Nair N, Dziedzic R, Greendyke R, Muniruzzaman S, Rajagopalan M, Madiraju MV. 2008
Synchronous replication initiation in novel Mycobacterium tuberculosis dnaA cold-sensitive mutants. Mol. Micro.: 71: 291-304.
- Yamamoto K, Moomey M, Rajagopalan M, Madiraju MV. 2008. Facilitation of dissociation reaction of nucleotides bound to Mycobacterium tuberculosis DnaA. J Biochem. ;143(6):759-64. 2008.
- Chen Y, Anderson DE, Rajagopalan M, Erickson, H. 2007. Assembly dynamics of Mycobacterium tuberculosis FtsZ. Journal of Biological Chemistry. 282(38):27736-43.
- Chauhan A, Lofton A, Maloney E, Fol M, Madiraju MV, Rajagopalan M. (2006) Interference of Mycobacterium tuberculosis cell division by Rv2719c, a cell-wall hydrolase. Molecular Microbiology 62(1):132-47.
- Fol M, Chauhan A, Maloney M, Moomey M, Madiraju M, Jagannath C. Rajagopalan M. Modulation of Mycobacterium tuberculosis proliferation by MtrA, an essential two-component response regulator. Molecular Microbiology 60(3): 643.
- Chauhan A, Madiraju VVS, Fol M, Lofton H, Maloney E, Reynolds R, Rajagopalan M. (2006). Mycobacterium tuberculosis cells growing in macrophages are filamentous and deficient in FtsZ rings. J. Bacteriology 188(5):1856.
- Madiraju MVVS, Moomey M, Neuenschwander P, Muniruzzamaman S, Yamamoto K, Grimwade J and Rajagopalan M. (2006) The intrinsic ATPase activity of Mycobacterium tuberculosis DnaA promotes rapid oligomerization of DnaA on oriC. Molecular Microbiology 59(6):1876.
- Murty V. Madiraju and M. Rajagopalan (2005). DNA Replication and Cell division Chapter for a book on Mycobacterial Molecular Microbiology. Horizon Press.
- Rajagopalan M, Maloney E, Dziadek J, Poplawska M, Lofton H, Chauhan A, Madiraju MV. (2005) Genetic evidence that mycobacterial FtsZ and FtsW proteins interact, and colocalize. FEMS Microbiol Lett. 2005 Sep 1; 250(1):9-17.
- Rajagopalan M, Atkinson MA, Lofton H, Chauhan A, Madiraju MV.(2005) Mutations in the GTP-binding and synergy loop domains of Mycobacterium tuberculosis. BBRC. 2005 Jun 17; 331