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Mary Jackson

Associate Professor
Director, Mycobacteria Research Laboratories

Lab Location: B426 Microbiology Building
Office: B423A Microbiology Building
Phone: (970)491-3582
Email:mary.jackson@colostate.edu

Research Interests and Accomplishments

Our research focuses on the biosynthetic pathways (enzymes and transporters) of major cell envelope components - (lipo)polysaccharides, (glyco)lipids, and fatty acids - playing important roles in the physiology and/or pathogenicity of Mycobacterium tuberculosis.

Other aspects of our research concern the development of novel anti-tuberculosis drugs and the study of the mechanisms of resistance of slow- and fast-growing mycobacteria of clinical interest to antibiotics and disinfectants.

In addition to providing fundamental knowledge about the biochemistry of M. tuberculosis and other mycobacteria, the broad goals of our work are (i) to determine the contribution of various cell envelope components to pathogenicity, (ii) to identify novel anti-tuberculosis drug targets and (iii) to generate novel attenuated mycobacterial strains as candidate live vaccines against tuberculosis.

Highlights from our work include the discovery of a number of enzymes (glycosyltransferases, acyltransferases, methyltransferases, polyketide synthases) and regulators involved in the biogenesis of mycobacterial glycoconjugates and the recognition of the pivotal role played by glycosyltransferases of the polyprenyl-phosphate-sugar-dependent class in particular in the building of the major cell envelope glycolipids and (lipo)polysaccharides, phosphatidylinositol mannosides, arabinogalactan and lipoarabinomannan. Another highlight was the discovery of a lipoprotein transporter (LppX) involved in the translocation of virulence-associated lipids (the phthiocerol dimycocerosates) to the cell surface of M. tuberculosis and the first demonstration that the translocation of complex lipids in mycobacteria involved mechanisms similar to those used by Gram negative bacteria to export lipoproteins to the outer membrane. In recent months, we elucidated how two old anti-TB drugs known as Isoxyl and Thiacetazone exert their bactericidal activity against M. tuberculosis and provided evidence that the RND transporter MmpL3 is required for the translocation to the periplasm of hallmark entities of the cell envelope of all mycobacteria: the mycolic acids. Importantly, the transport activity of MmpL3 is inhibited by several classes of anti-TB inhibitors including SQ109, an anti-TB compound presently undergoing phase II clinical trials.

The Lab (2012)

The Lab (2012)

Graduate Students

Winona Burgess - Combined DVM Residency/MS Program

Visiting Graduate Student

Jan Madacki

Post-doctoral Fellows

Emilie Huc-Claustre
Shiva Kumar Angala
Rabeb Dhouib
Juan Manuel Belardinelli
Wei Li

Research Associates

Vicki Jones - Lab Manager
Vinicius Calado Nogueira de Moura

Research Scientists

Anna Grzegorzewicz
William Wheat

Undergraduate Students

Sarah Born - HURS Student
Amanda Fairbanks - HURS Student
Kaylan Campbell
Alexander Babos
Alyssa Margolis

Publications (2007-2012)

Larrouy-Maumus, G., Škovierová, H., Dhouib, R., Angala, S. K., Zuberogoitia, S., Pham, H., Drumond Villela, A., Mikušová, K., Noguera, A., Gilleron, M., Valentinova, L., Korduláková, J., Brennan, P. J., Puzo, G., Nigou, J., and M. Jackson (2012) A small multidrug resistance-like transporter involved in the arabinosylation of arabinogalactan and lipoarabinomannan in mycobacteria. J. Biol. Chem. (in press).

Grzegorzewicz, A. E., J. Korduláková, V. Jones, S. E. M. Born, J. M. Belardinelli, A. Vaquié, V. A. K. B. Gundi, J. Madacki, N. Slama, F. Laval, J. Vaubourgeix, R. M. Crew, B. Gicquel, M. Daffé, H. R. Morbidoni, P. J. Brennan, A. Quémard, M. R. McNeil, and M. Jackson. (2012). A common mechanism of inhibition of the Mycobacterium tuberculosis mycolic acid biosynthetic pathway by Isoxyl and Thiacetazone. J. Biol. Chem. (in press).

Urresti, S., D. Albesa-Jove, F. Schaeffer, H. T. Pham, D. Kaur, P. Gest, M. J. van der Woerd, A. Carreras Gonzalez, S. Lopez Fernandez, P. M. Alzari, P. J. Brennan, M. Jackson, and M. E. Guerin (2012). Mechanistic insights into the retaining glucosyl-3-phosphoglycerate synthase from mycobacteria. J. Biol. Chem. 287(29):24649-24661.

Scherman, M. S., E. J. North, V. Jones, T. N. Hess, A. E. Grzegorzewicz, T. Kasagami, I.-H. Kim, O. Merzlikin, A. J. Lenaerts, R. E. Lee, M. Jackson, C. Morisseau, and M. R. McNeil (2012). Screening a library of 1,600 adamantyl ureas for anti-Mycobacterium tuberculosis activity in vitro and for better physical chemical properties for bioavailability. Bioorg. Med. Chem. 20(10): 3255-3262.

Klepp, L. I., M. A. Forrellad, A. V. Osella, F. Blanco, E. J. Stella, M. V. Bianco, M. P. Santangelo, C. Sassetti, M. Jackson, A. A. Cataldi, F. Bigi, and H. R. Morbidoni (2012). Impact of the deletion of the six mce operons in Mycobacterium smegmatis. Microbes and Infection 14(7-8) :590-599.

Grzegorzewicz, A. E., and Jackson M. (2012). Subfractionation and analysis of the cell envelope (lipo)polysaccharides of Mycobacterium tuberculosis. In A. H. Delcour (ed.), The Bacterial Cell Surface: Methods and Protocols. Humana Press, New York. (in press)

Grzegorzewicz, A. E., H. Pham, V. A. K. B. Gundi, M. S. Scherman, E. J. North, T. Hess, V. Jones, V. Gruppo, S. E. M. Born, J. Korduláková, S. S. Chavadi, C. Morisseau, A. J. Lenaerts, R. E. Lee, M. R. McNeil, and M. Jackson (2012) Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane. Nat. Chem. Biol. 8(4):334-341.

Fisher, C. W., A. Fiorello, D. Shaffer, M. Jackson, and G. E. McDonnell (2012). Aldehyde-resistant mycobacteria associated with the use of endoscope reprocessing systems. Am. J. Infect. Control (in press).

Santangelo, M. P., P. M. Gest, M. E. Guerin, M. Coinçon, H. Pham, G. Ryan, S. E. Puckett, J. S. Spencer, M. Gonzalez-Juarrero, R. Daher, A. J. Lenaerts, D. Schnappinger, M. Therisod, S. Ehrt, J. Sygusch, and M. Jackson (2011). Glycolytic and non-glycolytic functions of the fructose-1,6-bisphosphate aldolase of Mycobacterium tuberculosis, an essential enzyme produced by replicating and non-replicating bacilli. J. Biol. Chem. 286(46): 40219-40231.

Dianišková, P., J. Korduláková, H. Škovierová, D. Kaur, M. Jackson, P. J. Brennan, and K. Mikušová (2011). Investigation of ABC transporter from mycobacterial arabinogalactan biosynthetic cluster. Gen. Physiol. Biophys. 30:239-250.

Jackson, M., and Yamamoto, S. (2011). Chapter 1: Historical background of Mycobacterium bovis BCG, p. 3-12. In T. Takii, J. Maeyama, and S. Yamamoto (ed.), BCG − Vaccine and Adjuvant. Japan Anti-Tuberculosis Association, Tokyo, Japan.

Shang, S., S. Gibbs, M. Henao-Tamayo, C. A. Shanley, G. McDonnell, R. S. Duarte, D. J. Ordway, and M. Jackson (2011). Increased virulence of an epidemic strain of Mycobacterium massiliense in mice. PLoS ONE 6(9): e24726.

Brown, J. R., E. J. North, J. G. Hurdle, C. Morisseau, J. S. Scarborough, D. Sun, J. Korduláková, M. S. Scherman, V. Jones, A. Grzegorzewicz, R. M. Crew, M. Jackson, M. R. McNeil, and R. E. Lee (2011). The structure-activity relationship of urea derivatives as anti-tuberculosis agents. Bioorg Med Chem 19(18): 5585-5595.

Zhang, J., S. K. Angala, P. K. Pramanik, K. Li, D. C. Crick, A. Liav, A. Jozwiak, E. Swiezewska, M. Jackson, and D. Chatterjee (2011). Reconstitution of functional mycobacterial arabinosyltransferase AtfC proteoliposome and assessment of decaprenylphosphorylarabinose analogues as arabinofuranosyl donors. ACS Chemical Biology. 6: 819-828.

Škovierová, H., G. Larrouy-Maumus, H. Pham, M. Belanová, N. Barilone, A. DasGupta, K. Mikušová, B. Gicquel, M. Gilleron, P. J. Brennan, G. Puzo, J. Nigou, and M. Jackson (2010). Biosynthetic origin of the galactosamine substituent of arabinogalactan in Mycobacterium tuberculosis. J. Biol. Chem. 285(53): 41348-41355.

Termentzi, A., Khouri, I., Gaslonde, T., Prado, S., Saint-Joanis, B., Bardou, F., Amanatiadou, E. P., Vizirianakis, I. S., Korduláková, J., Jackson, M., Brosch, R., Janin, Y. L., Daffé, M., Tillequin, F., and Michel, S. (2010) Synthesis, biological activity, and evaluation of the mode of action of novel antitubercular benzofurobenzopyrans substituted on A ring. Eur. J. Med. Chem. 45(12): 5833-5847.

Guerin, M. E., J. Korduláková, P. M. Alzari, P. J. Brennan, and Jackson, M. (2010). Molecular basis of phosphatidylinositol mannoside biosynthesis and regulation in mycobacteria. J. Biol. Chem. 285: 33577-33583.

Daher, R., M. Coinçon, M. Fonvielle, P. Gest, M. Guerin, M. Jackson, J. Sygusch, and M. Thérisod (2010). Rational design, synthesis and evaluation of new selective inhibitors of microbial class II (zinc dependent) fructose bis-phosphate aldolases. J. Med. Chem. 53: 7836-7842.

Dasgupta, A., K. Sureka, D. Mitra, B. Saha, S. Sanyal, A. K. Das, P. Chakrabarti, M. Jackson, B. Gicquel, M. Kundu, and J. Basu (2010). An oligopeptide transporter of Mycobacterium tuberculosis regulates cytokine release and apoptosis of infected macrophages. PLoS ONE 5(8):e12225.

Christophe, T., M. Jackson, H. K. Jeon, D. Fenistein, M. Contreras Dominguez, J. Kim, A. Genovesio, J.-P. Carralot, F. Ewann, E. H. Kim, S. Y. Lee, S. Kang, M. J. Seo, E. J. Park, H. Škovierová, H. Pham, G. Riccardi, J. Y. Nam, L. Marsollier, M. Kempf, M.-L. Joly-Guillou, T. Oh, W. K. Shin, Z. No, U. Nehrbass, R. Brosch, S. T. Cole, and P. Brodin. (2009). High content screening identifies decaprenyl-phosphoribose 2' epimerase as a target for intracellular antimycobacterial inhibitors. PLoS Pathog. 5(10):e10000645.
doi:10.1371/journal.ppat.1000645.

Kaur, D., Pham, H., Larrouy-Maumus, G., Rivière, M., Vissa, V., Guerin, M. E., Puzo, G., Brennan, P. J. and Jackson, M. (2009) Initiation of methylglucose lipopolysaccharide biosynthesis in mycobacteria. PLoS ONE. 4(5): e5447. doi:10.1371/journal.pone.0005447.

Santangelo, M. P., L. Klepp, J. Nuñez-García, F. Blanco, M. Soria, M. del Carmen García-Pelayo, M. V. Bianco, A. Cataldi, P. Golby, M. Jackson, S. V. Gordon and F. Bigi. (2009) Mce3R, a TetR-type transcriptional repressor, controls the expression of a regulon involved in lipid metabolism in Mycobacterium tuberculosis. Microbiology. 155 : 2245-2255.

Guerin, M. E., Schaeffer, F., Chaffotte, A., Gest, P., Giganti, D., Korduláková, J., van der Woerd, M., Jackson, M. and Alzari, P. M. (2009) Substrate-induced conformational changes in the essential peripheral membrane-associated mannosyltransferase PimA from Mycobacteria. Implications for catalysis. J Biol Chem 284 : 21613-21625.

Svetlíková, Z., H. Škovierová, M. Niederweis, J.-L. Gaillard, G. McDonnell and Jackson, M. (2009) The role of porins in the susceptibility of Mycobacterium smegmatis and Mycobacterium chelonae to aldehyde-based disinfectants and drugs. Antimicrob Agents Chemother 53 : 4015-4018.

Škovierová, H., G. Larrouy-Maumus, J. Zhang, D. Kaur, N. Barilone, J. Korduláková, M. Gilleron, S. Guadagnini, M. Belanova, M.-C. Prevost, B. Gicquel, G. Puzo, D. Chatterjee, P. J. Brennan, J. Nigou, and Jackson, M. (2009) AftD, a novel essential arabinofuranosyltransferase from mycobacteria. Glycobiology 19: 1235-1247.

Guerin, M. E., D. Kaur, B. S. Somashekar, S. Gibbs, P. Gest, D. Chatterjee, P. J. Brennan, and Jackson, M. (2009) New insights into the early steps of phosphatidylinositol mannosides biosynthesis in mycobacteria. PimB' is an essential enzyme of Mycobacterium smegmatis. J. Biol. Chem. 284: 25687-25696.

Scherman, H., D. Kaur, H. Pham, H. Škovierová, M. Jackson, and P. J. Brennan. (2009) Identification of a polyprenylphosphomannosyl synthase involved in the synthesis of mycobacterial mannosides. J. Bacteriol. 191: 6769-6772.

Kaur, D., Guerin, M. E., Škovierová, H., Brennan, P. J. and Jackson, M. (2009) Biogenesis of the cell wall and other glycoconjugates of Mycobacterium tuberculosis. Advances in Applied Microbiology. 69: pp. 23-78.

Jackson, M., and Brennan, P.J. (2009) Polymethylated polysaccharides from Mycobacterium species revisited. J. Biol. Chem. 284: pp. 1949-1953.

Chesne-Seck, M.-L., N. Barilone, F. Boudou, J. Gonzalo Asensio, P. E. Kolattukudy, C. Martin, S. T. Cole, B. Gicquel, D. N. Gopaul, and Jackson, M. (2008). A point mutation in the two-component regulator PhoP-PhoR accounts for the absence of polyketide-derived acyltrehaloses but not that of phthiocerol dimycocerosates in Mycobacterium tuberculosis H37Ra J. Bact. 190, pp. 1329-1334.

Pitarque, S., Larrouy-Maumus, G., Payré, B., Jackson, M., Puzo, G., and Nigou, J. (2008) The immunomodulatory lipoglycans, lipoarabinomannan and lipomannan, are exposed at the mycobacterial cell surface. Tuberculosis 88, pp. 560-565.

Liav, A., Angala, S.K., Brennan, P.J., and Jackson, M. (2008) N-D-Aldopentofuranosyl-N’-[p-(isoamyloxy)phenyl]-thiourea derivatives: Potential anti-TB therapeutic agents. Bioorg. Med. Chem. Lett. 18: 2649-2651.

Fonvielle, M., Coincon, M., Daher, R., Desbenoit, N., Kosieradzka, K., Barilone, N., Gicquel, B., Sygusch, J., Jackson, M., and Therisod, M. (2008) Synthesis and biochemical evaluation of selective inhibitors of class II fructose bis-phosphate aldolases: towards new synthetic antibiotics. Chem. Eur. J. 14: 8521-8529.

Sambou, T., Dinadayala, P., Stadthagen, G., Barilone, N., Bordat, Y., Constant, P., Levillain, F., Neyrolles, O., Gicquel, B., Lemassu, A., Daffé, M., and Jackson, M. (2008) Capsular glucan and intracellular glycogen of Mycobacterium tuberculosis: Biosynthesis and impact on the persistence in mice. Mol. Microbiol. 70: 762-774.

Kaur, D., Obregón-Henao, A., Pham, H., Chatterjee, D., Brennan, P.J., and Jackson, M. (2008) Lipoarabinomannan of Mycobacterium; mannose capping by a multifunctional terminal mannosyltransferase. Proc. Natl. Acad. Sci. USA 105: 17973-17977.

Gest, P., Kaur, D., Pham, H.T., van der Woerd, M., Hansen, E., Brennan, P.J., Jackson, M., and Guerin, M.E. (2008) Preliminary crystallographic analysis of GpgS, a key glucosyltransferase involved in methylglucose lipopolysaccharide biosynthesis in Mycobacterium tuberculosis. Acta Crystallogr Sect F Struct Biol Cryst Commun F64: 1121–1124.

Gilleron, M., Jackson, M., Nigou, J., and Puzo, G. (2008) Structure, activities and biosynthesis of the Phosphatidyl-myo-Inositol-based lipoglycans In The Mycobacterial Cell Envelope: an overview. Editors: M. Daffé & J.-M. Reyrat; ASM Press, Washington DC. Chap. 6, 75-105.

Guerin, M.E., Korduláková, J., Schaeffer, F., Svetlikova, Z., Buschiazzo, A., Giganti, D., Gicquel, B., Mikusová, K., Jackson, M., and Alzari, P.M. (2007) Molecular recognition and interfacial catalysis by the essential phosphatidylinositol mannosyltransferase PimA from mycobacteria. J. Biol. Chem 282: 20705-20714.

Stadthagen, G., Sambou, T., Guerin, M., Barilone, N., Boudou, F., Korduláková, J., Charles, P., Alzari, P.M., Lemassu, A., Daffé, M., Puzo, G., Gicquel, B., Rivière, M., and Jackson, M. (2007) Genetic basis for the biosynthesis of methylglucose lipopolysaccharides in Mycobacterium tuberculosis. J. Biol. Chem. 282: 27270-27276.

Kaur, D., M. R. McNeil, K.-H. Khoo, D. Chatterjee, D. C. Crick, M. Jackson, and P. J. Brennan. (2007) New insights into the biosynthesis of mycobacterial lipomannan arising from deletion of a conserved gene. J. Biol. Chem 282:27133-27140.

Korduláková, J., Y. L. Janin, A. Liav, N. Barilone, T. Dos Vultos, J. Rauzier, P. J. Brennan, B. Gicquel, and M. Jackson. (2007) Isoxyl activation by EthA is required for bacteriostatic activity against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 51:3824-3829.

Jackson, M., Stadthagen, G., and Gicquel, B. (2007) Long-chain multiple methyl-branched fatty acid-containing lipids of Mycobacterium tuberculosis: biosynthesis, transport, regulation and biological activities. Tuberculosis 87 : 78-86.

Berg, S., D. Kaur, M. Jackson, and P. J. Brennan. (2007) The glycosyltransferases of Mycobacterium tuberculosis- roles in the synthesis of arabinogalactan, lipoarabinomannan, and other glycoconjugates. Glycobiology 17:35R-56R.

Marsollier, L., P. Brodin, M. Jackson, J. Korduláková, P. Tafelmeyer, E. Carbonnelle, J. Aubry, G. Milon, P. Legras, J.-P. Saint-Andre, C. Leroy, J. Cottin, M.-L. Joly Guillou, G. Reysset, and S. T. Cole. (2007) Impact of Mycobacterium ulcerans biofilm on tranmissibility to ecological niches and Buruli ulcer pathogenesis. PLoS Pathogens 3:e62.

Other Selected Publications

Kaur, D., Berg, S., Dinadayala, P., Gicquel, B., Chatterjee, D., McNeil, M.R., Vissa, V., Crick, D.C., Jackson, M., and Brennan, P.J. (2006) Biosynthesis of mycobacterial lipoarabinomannan: Role of a branching mannosyltransferase. Proc. Natl. Acad. Sci. USA 103: 13664-13669.

Sulzenbacher, G., Canaan, S., Bordat, Y., Neyrolles, O., Stadthagen, G., Roig-Zamboni, V., Rauzier, J., Maurin, D., Laval, F., Daffé, M., Cambillau, C., Gicquel, B., Bourne, Y., and Jackson, M. (2006) LppX is a lipoprotein required for the translocation of phthiocerol dimycocerosates to the surface of Mycobacterium tuberculosis. EMBO J. 25 : 1436-1444.

Gonzalo Asensio, J., Maia, C., Ferrer, N.L., Barilone, N., Laval, F., Soto, C., Winter, N., Daffé, M., Gicquel, B., Martin, C., and Jackson, M. (2006) The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 281: 1313-1316.

Rousseau, C., Winter, N., Pivert, E., Bordat, Y., Neyrolles, O., Avé, P., Huerre, M., Gicquel, B. and Jackson, M. (2004) Production of phthiocerol dimycocerosates protects Mycobacterium tuberculosis from the cidal activity of reactive nitrogen intermediates produced by macrophages and modulates the early immune response to infection. Cell. Microbiol., 6, 277-287.

Korduláková, J., Gilleron, M., Puzo, G., Brennan, P. J., Gicquel, B., Mikusová, K. and Jackson, M. (2003) Identification of the required acyltransferase step in the biosynthesis of the phosphatidylinositol mannosides of Mycobacterium species. J. Biol. Chem., 278, 36285-36295.

Korduláková, J., M. Gilleron, K. Mikusová, G. Puzo, P. J. Brennan, B. Gicquel, and M. Jackson (2002) Definition of the first mannosylation step in phosphatidylinositol synthesis: PimA is essential for growth of mycobacteria. J. Biol. Chem. 277, 31335-31344.

Raynaud, C., C. Guilhot, J. Rauzier, Y. Bordat, V. Pelicic, R. Manganelli, I. Smith, B. Gicquel, and M. Jackson (2002) Phospholipases C are involved in the virulence of Mycobacterium tuberculosis. Mol. Microbiol. 45, 203-217.

Jackson, M., Crick, D. C. and P. J. Brennan (2000) Phosphatidylinositol is an essential phospholipid of mycobacteria. J. Biol. Chem., 275, 30092-30099.

Jackson, M., Phalen, S. W., Lagranderie, M., Ensergueix, D., Chavarot, P., Marchal, G., McMurray, D. N., Gicquel, B. and C. Guilhot (1999) Persistence and protective efficacy of a Mycobacterium tuberculosis auxotroph vaccine. Infect. Immun., 67, 2867-2873.

Jackson, M., Raynaud, C., Lanéelle, M.-A., Guilhot, C., Laurent-Winter, C., Ensergueix, D., Gicquel B. and M. Daffé (1999) Inactivation of the antigen 85C gene profoundly affects the mycolate content and alters the permeability of the Mycobacterium tuberculosis cell envelope. Mol. Microbiol., 31, 1573-1587.

Pelicic, V., Jackson, M., Reyrat, J.-M., Jacobs Jr., W. R., Gicquel, B. and C. Guilhot (1997) Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci USA, 94, 10955-10960.

Research Support

Our research program is supported by grants from the National Institutes of Health / National Institute of Allergy and Infectious Diseases, and other for-profit and not-for-profit partners.

We collaborate with numerous academic and industrial partners both nationally and internationally.

Links

Mary Jackson Faculty Webpage

Video -Tuberculosis Research at CSU

Open Positions

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1619 Campus Delivery
Fort Collins, Colorado 80523-1619

Phone:
(970) 491-6144

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