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Requirement of the isocitrate lyase gene ICL1 for VPS41-mediated starvation response in Cryptococcus neoformans

  • Microbial Genetics, Genomics and Molecular Biology
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Abstract

Cryptococcus neoformans is a major cause of fungal meningitis in individuals with impaired immunity. Our previous studies have shown that the VPS41 gene plays a critical role in the survival of Cryptococcus neoformans under nitrogen starvation; however, the molecular mechanisms underlying VPS41-mediated starvation response remain to be elucidated. In the present study, we show that, under nitrogen starvation, VPS41 strongly enhanced ICL1 expression in C. neoformans and that overexpression of ICL1 in the vps41 mutant dramatically suppressed its defects in starvation response due to the loss of VPS41 function. Moreover, targeted deletion of ICL1 resulted in a dramatic decline in viability of C. neoformans cells under nitrogen deprivation. Taken together, our data suggest a model in which VPS41 up-regulates ICL1 expression, directly or indirectly, to promote survival of C. neoformans under nitrogen starvation.

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References

  • Chang, Y.C. and Kwon-Chung, K.J. 1994. Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence. Mol. Cell Biol. 14, 4912–4919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox, G.M., Mukherjee, J., Cole, G.T., Casadevall, A., and Perfect, J.R. 2000. Urease as a virulence factor in experimental cryptococcosis. Infect. Immun. 68, 443–448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dunn, M.F., Ramírez-Trujillo, J.A., and Hernández-Lucas, I. 2009. Major roles of isocitrate lyase and malate synthase in bacterial and fungal pathogenesis. Microbiology 155, 3166–3175.

    Article  CAS  PubMed  Google Scholar 

  • Erickson, T., Liu, L., Gueyikian, A., Zhu, X., Gibbons, J., and Williamson, P.R. 2001. Multiple virulence factors of Cryptococcus neoformans are dependent on VPH1. Mol. Microbiol. 42, 1121–1131.

    Article  CAS  PubMed  Google Scholar 

  • Fernandez, E., Moreno, F., and Rodicio, R. 1992. The ICL1 gene from Saccharomyces cerevisiae. Eur. J. Biochem. 204, 983–990.

    Article  CAS  PubMed  Google Scholar 

  • Hu, G.W., Hacham, M., Waterman, S.R., Panepinto, J., Shin, S., Liu, X., Gibbons, J., Valyi-Nagy, T., Obara, K., Jaffe, H.A., et al. 2008. PI3K signaling of autophagy is required for starvation tolerance and virulence of Cryptococcus neoformans. J. Clin. Invest. 118, 1186–1197.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Idnurm, A. and Howlett, B.J. 2002. Isocitrate lyase is essential for pathogenicity of the fungus Leptosphaeria maculans to Canola (Brassica napus). Eukaryot. Cell 1, 719–724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeon, J.M., Lee, H.I., Sadowsky, M.J., Sugawara, M., and Chang, W.S. 2015. Characterization of a functional role of the Bradyrhizobium japonicum isocitrate lyase in desiccation tolerance. Int. J. Mol. Sci. 16, 16695–16709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung, W.H. and Kronstad, J.W. 2008. Iron and fungal pathogenesis: a case study with Cryptococcus neoformans. Cell. Microbiol. 10, 277–284.

    Article  CAS  PubMed  Google Scholar 

  • Kwon-Chung, K.J., Polacheck, I., and Popkin, T.J. 1982. Melaninlacking mutants of Cryptococcus neoformans and their virulence for mice. J. Bacteriol. 150, 1414–1421.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lindsey, T.L., Hagins, J.M., Sokol, P.A., and Silo-Suh, L.A. 2008. Virulence determinants from a cystic fibrosis isolate of Pseudomonas aeruginosa include isocitrate lyase. Microbiology 154, 1616–1627.

    Article  CAS  PubMed  Google Scholar 

  • Liu, X.G., Hu, G.W., Panepinto, J., and Williamson, P.R. 2006. Role of a VPS41 homologue in starvation response, intracellular survival and virulence of Cryptococcus neoformans. Mol. Microbiol. 61, 1132–1146.

    Article  CAS  PubMed  Google Scholar 

  • Liu, X., Li, W., and Ye, D. 2015. Digital gene expression profiling of vps41Δ of Cryptococcus neoformans under nitrogen starvation. J. Tianjin Univ. Sci. Technol. 30, 14–18. (in Chinese)

    Google Scholar 

  • Lorenz, M.C. and Fink, G.R. 2001. The glyoxylate cycle is required for fungal virulence. Nature 412, 83–86.

    Article  CAS  PubMed  Google Scholar 

  • Lorenz, M.C. and Fink, G.R. 2002. Life and death in a macrophage: role of the glyoxylate cycle in virulence. Eukaryot. Cell 1, 657–662.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McKinney, J.D., Honer zu Bentrup, K., Munoz-Elias, E.J., Miczak, A., Chen, B., Chan, W.T., Swenson, D., Sacchettini, J.C., Jacobs, W.R.Jr., and Russell, D.G. 2000. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406, 735–738.

    Article  CAS  PubMed  Google Scholar 

  • Mitchell, T.G. and Perfect, J.R. 1995. Cryptococcosis in the era of AIDS-100 years after the discovery of Cryptococcus neoformans. Clin. Microbiol. Rev. 8, 515–548.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Odom, A., Muir, S., Lim, E., Toffaletti, D.L., Perfect, J., and Heitman, J. 1997 Calcineurin is required for virulence of Cryptococcus neoformans. EMBO J. 16, 2576–2589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park, B.J., Wannemuehler, K.A., Marston, B.J., Govender, N., Pappas, P.G., and Chiller, T.M. 2009. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23, 525–530.

    Article  PubMed  Google Scholar 

  • Ramirez, M.A. and Lorenz, C.M. 2006. Mutations in alternative carbon utilization pathways in Candida albicans attenuate virulence and confer pleiotropic phenotypes. Eukaryot. Cell 6, 280–290.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rude, T.H., Toffaletti, D.L., Cox, G.M., and Perfect, J.R. 2002. Relationship of the glyoxylate pathway to the pathogenesis of Cryptococcus neoformans. Infect. Immun. 70, 5684–5694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salas, S.D., Bennett, J.E., Kwon-Chung, K.J., Perfect, J.R., and Williamson, P.R. 1996. Effect of the laccase gene CNLAC1 on virulence of Cryptococcus neoformans. J. Exp. Med. 184, 377–386.

    Article  CAS  PubMed  Google Scholar 

  • Wall, D.M., Duffy, P.S., DuPont, C., Prescott, J.F., and Meijer, W.G. 2005. Isocitrate lyase activity is required for virulence of the intracellular pathogen Rhodococcus equi. Infect. Immun. 73, 6736–6741.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Xiaoguang Liu.

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Xu, Z., Zhi, Y., Dong, J. et al. Requirement of the isocitrate lyase gene ICL1 for VPS41-mediated starvation response in Cryptococcus neoformans . J Microbiol. 54, 487–491 (2016). https://doi.org/10.1007/s12275-016-6177-6

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  • DOI: https://doi.org/10.1007/s12275-016-6177-6

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