The Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response to antifungal drugs and loss of calcineurin function
Open accessAbstract
Summary: Cell wall integrity is crucial for fungal growth, development and stress survival. In the model yeast Saccharomyces cerevisiae, the cell integrity Mpk1/Slt2 MAP kinase and calcineurin pathways monitor cell wall integrity and promote cell wall remodelling under stress conditions. We have identified the Cryptococcus neoformans homologue of the S. cerevisiae Mpk1/Slt2 MAP kinase and have characterized its role in the maintenance of cell integrity in response to elevated growth temperature and in the presence of cell wall synthesis inhibitors. C. neoformans Mpk1 is required for growth at 37°C in vitro, and this growth defect is suppressed by osmotic stabilization. C. neoformans mutants lacking Mpk1 are attenuated for virulence in the mouse model of cryptococcosis. Phosphorylation of Mpk1 is induced in response to perturbations of cell wall biosynthesis by the antifungal drugs nikkomycin Z (a chitin synthase inhibitor), caspofungin (a β‐1,3‐glucan synthase inhibitor), or FK506 (a calcineurin inhibitor), and mutants lacking Mpk1 display enhanced sensitivity to nikkomycin Z and caspofungin. Lastly, we show that calcineurin and Mpk1 play complementing roles in regulating cell integrity in C. neoformans. Our studies demonstrate that pharmacological inhibition of the cell integrity pathway would enhance the activity of antifungal drugs that target the cell wall.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The C. glabrata Δcnb1 strain phenotype (increased susceptibility to azoles and cell wall-damaging agents, decreased virulence) is consistent with previous findings for other pathogenic fungi.
“For example, the observed C. glabrata Δcnb1 strain phenotype, which is characterized by an increased susceptibility to azoles and cell wall-damaging agents as well as decreased virulence, is consistent with previous findings for other pathogenic fungi, such as C. albicans (2-4, 27), C. neoformans (11, 18, 21), and A. fumigatus (9, 30).”
From Roles of Calcineurin and Crz1 in Antifungal Susceptibility and Virulence of <i>Candida glabrata</i> (2010) · cites this paper as [18]
The C. albicans cnb1 mutant showed filamentous growth in vivo but failed to grow in a mouse model of disseminated candidiasis and was unable to survive in serum, revealing evolutionarily distinct control aspects of calcineurin over virulence of two divergent fungal pathogens via distinct mechanisms.
“Although the C. albicans cnb1 mutant strain showed filamentous growth in vivo, it failed to grow in a mouse model of disseminated candidiasis and was unable to survive in serum, revealing evolutionarily distinct control aspects of calcineurin over virulence of two divergent fungal pathogens via distinct mechanisms (Blankenship and Heitman, 2005; Blankenship et al., 2003; Kraus et al., 2003).”
From Calcineurin as a multifunctional regulator: Unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis (2014) · cites this paper as Kraus et al., 2003
Cites
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L. (1991) · Cell · doi:10.1016/0092-8674(91)90124-h · Cited by 4,116 · see citing works
Sherman, F. (1991) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(91)94004-v · Cited by 4,078 · see citing works
Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry
Ho, Y., Gruhler, A., Heilbut, A. M., Bader, G. D., Moore, L., Adams, S., Millar, A., Taylor, P. P., Bennett, K. L., Boutilier, K., et al. (2002) · Nature · doi:10.1038/415180a · Cited by 3,573 · see citing works
Cobb, M. H., & Goldsmith, E. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.25.14843 · Cited by 1,718 · see citing works
MAP Kinase Pathways in the YeastSaccharomyces cerevisiae
Gustin, M., Albertyn, J., Alexander, M., & Davenport, K. (1998) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.62.4.1264-1300.1998 · Cited by 1,010 · see citing works
Dynamics of cell wall structure in Saccharomyces cerevisiae
Klis, F. M., Mol, P. C., Hellingwerf, K. J., & Brul, S. (2002) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2002.tb00613.x · Cited by 1,007 · see citing works
Casadevall, A., & Perfect, J. R. (1998) · ASM Press eBooks · doi:10.1128/9781555818241 · Cited by 673 · see citing works
Calcineurin is required for virulence of Cryptococcus neoformans
Odom, A., Muir, S., Lim, E., Toffaletti, D. L., Perfect, J., & Heitman, J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.10.2576 · Cited by 516 · see citing works
Self-citationChapter 19 Fluorescence Microscopy Methods for Yeast
Pringle, J. R., Preston, R. A., Adams, A. E. M., Stearns, T., Drubin, D. G., Haarer, B. K., & Jones, E. W. (1989) · Methods in cell biology · doi:10.1016/s0091-679x(08)61620-9 · Cited by 514 · see citing works
Kamada, Y., Jung, U. S., Piotrowski, J., & Levin, D. E. (1995) · Genes & Development · doi:10.1101/gad.9.13.1559 · Cited by 488 · see citing works
Xu, J., Staiger, C. J., & Hamer, J. E. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.21.12713 · Cited by 460 · see citing works
Jung, U. S., & Levin, D. E. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01667.x · Cited by 424 · see citing works
Douglas, C. M., Foor, F., Marrinan, J. A., Morin, N., Nielsen, J. B., Dahl, A. M., Mazur, P., Baginsky, W., Li, W., & el-Sherbeini, M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.26.12907 · Cited by 401 · see citing works
A Yeast Mitogen-Activated Protein Kinase Homolog (Mpk1p) Mediates Signalling by Protein Kinase C
Lee, K. S., Irie, K., Gotoh, Y., Watanabe, Y., Araki, H., Nishida, E., Matsumoto, K., & Levin, D. E. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.5.3067 · Cited by 377 · see citing works
Lussier, M., White, A.-M., Sheraton, J., DiPaolo, T., Treadwell, J. A., Southard, S. B., Horenstein, C. I., Chen-Weiner, J., Ram, A. F. J., Kapteyn, J. C., et al. (1997) · Genetics · doi:10.1093/genetics/147.2.435 · Cited by 369 · see citing works
Verna, J., Lodder, A., Lee, K., Vagts, A. J., & Ballester, R. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.25.13804 · Cited by 366 · see citing works
The Yeast Cell Wall and Septum as Paradigms of Cell Growth and Morphogenesis
Cabib, E., Roh, D.-H., Schmidt, M., Crotti, L. B., & Varma, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.r000031200 · Cited by 344 · see citing works
Douglas, C. M., D'Ippolito, J. A., Shei, G.-J., Meinz, M., Onishi, J. C., Marrinan, J. A., Li, W., Abruzzo, G. K., Flattery, A. M., Bartizal, K. F., et al. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.11.2471 · Cited by 344 · see citing works
Martı́n, H., Rodrı́guez-Pachón, J. M., Ruiz, C., Nombela, C., & Molina, M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.2.1511 · Cited by 343 · see citing works
Melanin-lacking mutants of Cryptococcus neoformans and their virulence for mice
Kwon-Chung, K. J., Polacheck, I., & Popkin, T. J. (1982) · Journal of Bacteriology · doi:10.1128/jb.150.3.1414-1421.1982 · Cited by 327 · see citing works
Heinisch, J. J., Lorberg, A., Schmitz, H., & Jacoby, J. J. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01375.x · Cited by 322 · see citing works
A PCR-based strategy to generate integrative targeting alleles with large regions of homology
Davidson, R. C., Blankenship, J. R., Kraus, P. R., de Jesús-Berrı́os, M., Hull, C. M., D’Souza, C. A., Wang, P., & Heitman, J. (2002) · Microbiology · doi:10.1099/00221287-148-8-2607 · Cited by 296 · see citing works
Self-citationActivation of Yeast Protein Kinase C by Rho1 GTPase
Kamada, Y., Qadota, H., Python, C. P., Anraku, Y., Ohya, Y., & Levin, D. E. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.16.9193 · Cited by 280 · see citing works
de Nobel, H., Ruiz, C., Martı́n, H., Morris, W. L., Brul, S., Molina, M., & Klis, F. M. (2000) · Microbiology · doi:10.1099/00221287-146-9-2121 · Cited by 269 · see citing works
Compounds active against cell walls of medically important fungi
Hector, R. F. (1993) · Clinical Microbiology Reviews · doi:10.1128/cmr.6.1.1 · Cited by 242 · see citing works
Gray, J. V., Ogas, J. P., Kamada, Y., Stone, M., Levin, D. E., & Herskowitz, I. (1997) · The EMBO Journal · doi:10.1093/emboj/16.16.4924 · Cited by 224 · see citing works
Zhao, C., Jung, U. S., Garrett-Engele, P., Roe, T., Cyert, M. S., & Levin, D. E. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.2.1013 · Cited by 209 · see citing works
Decreased virulence in stable, acapsular mutants ofCryptococcus neoformans
Fromtling, R. A., Shadomy, H. J., & Jacobson, E. S. (1982) · Mycopathologia · doi:10.1007/bf00636177 · Cited by 202 · see citing works
Thompson, J. R., Douglas, C. M., Li, W., Jue, C. K., Pramanik, B., Yuan, X., Rude, T. H., Toffaletti, D. L., Perfect, J. R., & Kurtz, M. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.2.444-453.1999 · Cited by 196 · see citing works
A protein kinase gene complements the lytic phenotype of Saccharomyces cerevisiae lyt2 mutants
Torres, L., Martı́n, H., García-Sáez, M. I., Arroyo, J., Molina, M., Sánchez, M., & Nombela, C. (1991) · Molecular Microbiology · doi:10.1111/j.1365-2958.1991.tb01993.x · Cited by 191 · see citing works
Garrett-Engele, P. W., Moilanen, B., & Cyert, M. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.8.4103 · Cited by 187 · see citing works
Navarro-García, F., Sánchez, M., Plá, J., & Nombela, C. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.4.2197 · Cited by 182 · see citing works
Fox, D. S., Cruz, M. C., Sia, R. A. L., Ke, H., Cox, G. M., Cardenas, M. E., & Heitman, J. (2001) · Molecular Microbiology · doi:10.1046/j.1365-2958.2001.02295.x · Cited by 175 · see citing works
Self-citationDel Poeta, M., Cruz, M. C., Cardenas, M. E., Perfect, J. R., & Heitman, J. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.3.739-746.2000 · Cited by 169 · see citing works
Self-citationCruz, M. C., Cavallo, L. M., Görlach, J. M., Cox, G. M., Perfect, J. R., Cardenas, M. E., & Heitman, J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.6.4101 · Cited by 168 · see citing works
Self-citationPoeta, M. D., Schell, W. A., & Perfect, J. R. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.8.1835 · Cited by 165 · see citing works
Update on antifungals targeted to the cell wall: focus on β-1,3-glucan synthase inhibitors
Georgopapadakou, N. H. (2001) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.10.2.269 · Cited by 149 · see citing works
Activity of the yeast MAP kinase homologue Slt2 is critically required for cell integrity at 37° C
Martı́n, H., Arroyo, J., Sánchez, M., Molina, M., & Nombela, C. (1993) · Molecular and General Genetics MGG · doi:10.1007/bf00280215 · Cited by 148 · see citing works
Gaughran, J. P., LAI, M. H., Kirsch, D. R., & Silverman, S. J. (1994) · Journal of Bacteriology · doi:10.1128/jb.176.18.5857-5860.1994 · Cited by 148 · see citing works
A role for the Pkc1p/Mpk1p kinase cascade in the morphogenesis checkpoint
Harrison, J. C., Bardes, E. S. G., Ohya, Y., & Lew, D. J. (2001) · Nature Cell Biology · doi:10.1038/35070104 · Cited by 145 · see citing works
Good fungi gone bad: The corruption of calcineurin
Fox, D. S., & Heitman, J. (2002) · BioEssays · doi:10.1002/bies.10157 · Cited by 137 · see citing works
Self-citationFeldmesser, M., Kress, Y., Mednick, A. J., & Casadevall, A. (2000) · The Journal of Infectious Diseases · doi:10.1086/317614 · Cited by 130 · see citing works
A Yeast Mitogen-Activated Protein Kinase Homolog (Mpk1p) Mediates Signalling by Protein Kinase C
Lee, K. S., Irie, K., Gotoh, Y., et al. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.5.3067-3075.1993 · Cited by 127 · see citing works
Diez‐Orejas, R., Molero, G., Navarro-García, F., Plá, J., Nombela, C., & Sánchez‐Pérez, M. (1997) · Infection and Immunity · doi:10.1128/iai.65.2.833-837.1997 · Cited by 120 · see citing works
Spm1, a stress‐activated MAP kinase that regulates morphogenesis in S.pombe
Zaitsevskaya-Carter, T., & Cooper, J. A. (1997) · The EMBO Journal · doi:10.1093/emboj/16.6.1318 · Cited by 117 · see citing works
Roemer, T., Delaney, S., & Bussey, H. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.7.4039 · Cited by 117 · see citing works
Waugh, M. S., Nichols, C. B., DeCesare, C. M., Cox, G. M., Heitman, J., & Alspaugh, J. A. (2002) · Microbiology · doi:10.1099/00221287-148-1-191 · Cited by 104 · see citing works
Self-citationJacoby, J. J., Nilius, S. M., & Heinisch, J. J. (1998) · Molecular and General Genetics MGG · doi:10.1007/s004380050717 · Cited by 104 · see citing works
Cruz, M. C., Sia, R. A. L., Olson, M. E., Cox, G. M., & Heitman, J. (2000) · Infection and Immunity · doi:10.1128/iai.68.2.982-985.2000 · Cited by 75 · see citing works
Self-citationCaspofungin acetate: An antifungal agent
Hoang, A. D. (2001) · American Journal of Health-System Pharmacy · doi:10.1093/ajhp/58.13.1206 · Cited by 68 · see citing works
Inhibitory effect of nikkomycin Z on chitin synthases in Candida albicans
Kim, M. K., Park, H., Kim, C. H., Park, H., & Choi, W. (2002) · Yeast · doi:10.1002/yea.837 · Cited by 58 · see citing works
Calcineurin phosphatase in signal transduction: lessons from fission yeast
Sugiura, R., Sio, S. O., Shuntoh, H., & Kuno, T. (2002) · Genes to Cells · doi:10.1046/j.1365-2443.2002.00557.x · Cited by 58 · see citing works
Nelson, P. W., Lozano‐Chiu, M., & Rex, J. H. (1997) · Medical Mycology · doi:10.1080/02681219780001291 · Cited by 52 · see citing works
Roemer, T., Delaney, S., & Bussey, H. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.7.4039-4048.1993 · Cited by 35 · see citing works
Total number of coding open reading frames in the yeast genome
Kowalczuk, M., Mackiewicz, P., Gierlik, A., Dudek, M. R., & Cebrat, S. (1999) · Yeast · doi:10.1002/(sici)1097-0061(199908)15:11 · Cited by 34 · see citing works
Fox, D. S., & Smulian, A. G. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01606.x · Cited by 34 · see citing works
Self-citationProperties of Various RHO1 Mutant Alleles of Cryptococcus neoformans
Chang, Y. C., & Penoyer, L. A. (2000) · Journal of Bacteriology · doi:10.1128/jb.182.17.4987-4991.2000 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Regulatory circuitry governing fungal development, drug resistance, and disease.
Shapiro, R. S., Robbins, N., & Cowen, L. E. (2011) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00045-10 · Cited by 576 · see citing works
Bayram, Ö., & Braus, G. H. (2011) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2011.00285.x · Cited by 551 · see citing works
Stimulation of Chitin Synthesis Rescues Candida albicans from Echinocandins
Walker, L. A., Munro, C. A., de Bruijn, I., Lenardon, M. D., McKinnon, A., & Gow, N. A. R. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000040 · Cited by 445 · see citing works
Aspergillus fumigatus: saprophyte or pathogen?
Tekaia, F., & Latgé, J.-P. (2005) · Current Opinion in Microbiology · doi:10.1016/j.mib.2005.06.017 · Cited by 387 · see citing works
Mitogen-Activated Protein Kinase Pathways and Fungal Pathogenesis
Zhao, X., Mehrabi, R., & Xu, J. (2007) · Eukaryotic Cell · doi:10.1128/ec.00216-07 · Cited by 367 · see citing works
The Cryptococcus neoformans Capsule: a Sword and a Shield
O’Meara, T. R., & Alspaugh, J. A. (2012) · Clinical Microbiology Reviews · doi:10.1128/cmr.00001-12 · Cited by 365 · see citing works
(2014) · doi:10.1128/cmr.00126-13 · Cited by 437 · see citing works
Deciphering the Model Pathogenic Fungus Cryptococcus Neoformans
Idnurm, A., Bahn, Y., Nielsen, K., Lin, X., Fraser, J. A., & Heitman, J. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1245 · Cited by 337 · see citing works
Self-citationHarnessing calcineurin as a novel anti-infective agent against invasive fungal infections.
Steinbach, W. J., Reedy, J. L., Cramer, R. A., Perfect, J. R., & Heitman, J. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1680 · Cited by 313 · see citing works
Self-citationStress, drugs, and evolution: the role of cellular signaling in fungal drug resistance.
Cowen, L. E., & Steinbach, W. J. (2008) · Eukaryotic Cell · doi:10.1128/ec.00041-08 · Cited by 285 · see citing works
Bahn, Y., Kojima, K., Cox, G. M., & Heitman, J. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-11-0987 · Cited by 274 · see citing works
Self-citationFuchs, B. B., & Mylonakis, E. (2009) · Eukaryotic Cell · doi:10.1128/ec.00193-09 · Cited by 266 · see citing works
Basic principles of the virulence of <i>Cryptococcus</i>
Zaragoza, O. (2019) · Virulence · doi:10.1080/21505594.2019.1614383 · Cited by 249 · see citing works
Mitogen-Activated Protein Kinase Signaling
Kyosseva, S. V. (2004) · International review of neurobiology · doi:10.1016/s0074-7742(04)59008-6 · Cited by 234 · see citing works
Jung, W. H., Sham, A. P., White, R., & Kronstad, J. W. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040410 · Cited by 222 · see citing works
Doering, T. L. (2009) · Annual Review of Microbiology · doi:10.1146/annurev.micro.62.081307.162753 · Cited by 220 · see citing works
A contact-activated kinase signals Candida albicans invasive growth and biofilm development
Kumamoto, C. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407097102 · Cited by 210 · see citing works
Opitz, C., & Soldati‐Favre, D. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.03056.x · Cited by 209 · see citing works
Reinoso-Martín, C., Schüller, C., Schuetzer-Muehlbauer, M., & Kuchler, K. (2003) · Eukaryotic Cell · doi:10.1128/ec.2.6.1200-1210.2003 · Cited by 193 · see citing works
Lamping, E., Monk, B. C., Niimi, K., Holmes, A. R., Tsao, S., Tanabe, K., Niimi, M., Uehara, Y., & Cannon, R. D. (2007) · Eukaryotic Cell · doi:10.1128/ec.00091-07 · Cited by 192 · see citing works
New Horizons in Antifungal Therapy
Pianalto, K. M., & Alspaugh, J. A. (2016) · Journal of Fungi · doi:10.3390/jof2040026 · Cited by 195 · see citing works
Cryptococcus neoformans Virulence Gene Discovery through Insertional Mutagenesis
Idnurm, A., Reedy, J. L., Nussbaum, J. C., & Heitman, J. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.2.420-429.2004 · Cited by 185 · see citing works
Self-citationValiante, V., Macheleidt, J., Föge, M., & Brakhage, A. A. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00325 · Cited by 184 · see citing works
Reese, A. J., Yoneda, A., Breger, J. A., Beauvais, A., Liu, H., Griffith, C. L., Bose, I., Kim, M., Skau, C., Yang, S., et al. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05551.x · Cited by 183 · see citing works
Master and Commander in Fungal Pathogens: the Two-Component System and the HOG Signaling Pathway
Bahn, Y. (2008) · Eukaryotic Cell · doi:10.1128/ec.00323-08 · Cited by 175 · see citing works
Juvvadi, P. R., Lee, S. C., Heitman, J., & Steinbach, W. J. (2016) · Virulence · doi:10.1080/21505594.2016.1201250 · Cited by 172 · see citing works
Self-citationCoping with stress: calmodulin and calcineurin in model and pathogenic fungi
Kraus, P. R., & Heitman, J. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01528-6 · Cited by 169 · see citing works
Self-citationThermotolerance and virulence of Aspergillus fumigatus : role of the fungal nucleolus
Bhabhra, R., & Askew, D. S. (2005) · Medical Mycology · doi:10.1080/13693780400029486 · Cited by 168 · see citing works
Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans
Lee, K.-T., So, Y.-S., Yang, D., Jung, K.-W., Choi, J., Lee, D., Kwon, H., Jang, J., Wang, L. L., Cha, S., et al. (2016) · Nature Communications · doi:10.1038/ncomms12766 · Cited by 166 · see citing works
Self-citationMpkA-Dependent and -Independent Cell Wall Integrity Signaling in Aspergillus nidulans
Fujioka, T., Mizutani, O., Furukawa, K., Sato, N., Yoshimi, A., Yamagata, Y., Nakajima, T., & Abe, K. (2007) · Eukaryotic Cell · doi:10.1128/ec.00281-06 · Cited by 161 · see citing works
MAP kinase pathways as regulators of fungal virulence
Román, E., Arana, D. M., Nombela, C., Alonso‐Monge, R., & Plá, J. (2007) · Trends in Microbiology · doi:10.1016/j.tim.2007.02.001 · Cited by 158 · see citing works
Valiante, V., Heinekamp, T., Jain, R., Härtl, A., & Brakhage, A. A. (2007) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2007.09.006 · Cited by 153 · see citing works
Fungal heat-shock proteins in human disease
Burnie, J., Carter, T. L., Hodgetts, S. J., & Matthews, R. (2005) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2005.00001.x · Cited by 158 · see citing works
Signalling pathways in the pathogenesis of Cryptococcus
Kozubowski, L., Lee, S. C., & Heitman, J. (2008) · Cellular Microbiology · doi:10.1111/j.1462-5822.2008.01273.x · Cited by 150 · see citing works
Self-citationCell wall integrity is dependent on the PKC1 signal transduction pathway in Cryptococcus neoformans
Gerik, K. J., Donlin, M. J., Soto, C. E., Banks, A. M., Banks, I. R., Maligie, M. A., Selitrennikoff, C. P., & Lodge, J. K. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.04843.x · Cited by 146 · see citing works
Cell wall integrity signalling in human pathogenic fungi: CWI signalling in pathogenic fungi
Dichtl, K., Samantaray, S., & Wagener, J. (2016) · Cellular Microbiology · doi:10.1111/cmi.12612 · Cited by 144 · see citing works
Cryptococcus neoformans, a fungus under stress
Brown, S. M., Campbell, L. T., & Lodge, J. K. (2007) · Current Opinion in Microbiology · doi:10.1016/j.mib.2007.05.014 · Cited by 144 · see citing works
Yin, Z., Feng, W., Chen, C., Xu, J., Li, Y., Yang, L., Wang, J., Liu, X., Wang, W., Gao, C., et al. (2019) · Autophagy · doi:10.1080/15548627.2019.1644075 · Cited by 131 · see citing works
Kojima, K., Bahn, Y., & Heitman, J. (2006) · Microbiology · doi:10.1099/mic.0.28571-0 · Cited by 125 · see citing works
Self-citationCryptococcus neoformans: the yeast that likes it hot
Perfect, J. R. (2006) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2006.00051.x · Cited by 122 · see citing works
Mehrabi, R., van der Lee, T., Waalwijk, C., & Kema, G. H. J. (2006) · Molecular Plant-Microbe Interactions · doi:10.1094/mpmi-19-0389 · Cited by 120 · see citing works
Comprehensive genomic analysis of cell wall genes in Aspergillus nidulans
de Groot, P. W. J., Brandt, B. W., Horiuchi, H., Ram, A. F. J., de Koster, C. G., & Klis, F. M. (2009) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2008.07.022 · Cited by 117 · see citing works
Juvvadi, P. R., Lamoth, F., & Steinbach, W. J. (2014) · Fungal Biology Reviews · doi:10.1016/j.fbr.2014.02.004 · Cited by 116 · see citing works
Segorbe, D., Pietro, A. D., Pérez‐Nadales, E., & Turrà, D. (2016) · Molecular Plant Pathology · doi:10.1111/mpp.12446 · Cited by 116 · see citing works
Multiple Signaling Pathways Regulate Yeast Cell Death during the Response to Mating Pheromones
Zhang, N.-N., Dudgeon, D. D., Paliwal, S., Levchenko, A., Grote, E., & Cunningham, K. W. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-03-0177 · Cited by 115 · see citing works
Iron‐regulated transcription and capsule formation in the fungal pathogen Cryptococcus neoformans
Lian, T., Simmer, M. I., D’Souza, C. A., Steen, B. R., Zuyderduyn, S., Jones, S. J. M., Marra, M. A., & Kronstad, J. W. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04474.x · Cited by 113 · see citing works
Curcumin Targets Cell Wall Integrity via Calcineurin-Mediated Signaling in Candida albicans
Kumar, A., Dhamgaye, S., Maurya, I. K., Singh, A., Sharma, M., & Prasad, R. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01385-13 · Cited by 111 · see citing works
Chapter 5 Virulence in Cryptococcus Species
Ma, H., & May, R. C. (2009) · Advances in applied microbiology · doi:10.1016/s0065-2164(08)01005-8 · Cited by 112 · see citing works
Identification of Cryptococcus neoformans Temperature-Regulated Genes with a Genomic-DNA Microarray
Kraus, P. R., Boily, M.-J., Giles, S. S., Stajich, J., Allen, A., Cox, G. M., Dietrich, F. S., Perfect, J. R., & Heitman, J. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.5.1249-1260.2004 · Cited by 109 · see citing works
Self-citationYun, Y., Liu, Z., Zhang, J., Shim, W., Chen, Y., & Ma, Z. (2013) · Environmental Microbiology · doi:10.1111/1462-2920.12334 · Cited by 109 · see citing works
Cramer, K. L., Gerrald, Q. D., Nichols, C. B., Price, M. S., & Alspaugh, J. A. (2006) · Eukaryotic Cell · doi:10.1128/ec.00145-06 · Cited by 106 · see citing works
Crosstalk between PKA and PKG controls pH‐dependent host cell egress of Toxoplasma gondii
Jia, Y., Marq, J., Bisio, H., Jacot, D., Mueller, C., Yu, L., Choudhary, J. S., Brochet, M., & Soldati‐Favre, D. (2017) · The EMBO Journal · doi:10.15252/embj.201796794 · Cited by 107 · see citing works
Cryptococcus neoformans : A sugar-coated killer with designer genes
Perfect, J. R. (2005) · FEMS Immunology & Medical Microbiology · doi:10.1016/j.femsim.2005.06.005 · Cited by 104 · see citing works
Gerik, K. J., Bhimireddy, S. R., Ryerse, J. S., Specht, C. A., & Lodge, J. K. (2008) · Eukaryotic Cell · doi:10.1128/ec.00146-08 · Cited by 107 · see citing works
Park, G., Pan, S., & Borkovich, K. A. (2008) · Eukaryotic Cell · doi:10.1128/ec.00466-07 · Cited by 106 · see citing works
Cryptococcal pathogenic mechanisms: a dangerous trip from the environment to the brain
Esher, S. K., Zaragoza, Ó., & Alspaugh, J. A. (2018) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/0074-02760180057 · Cited by 104 · see citing works
Ngamskulrungroj, P., Himmelreich, U., Breger, J. A., Wilson, C. F., Chayakulkeeree, M., Krockenberger, M. B., Malík, R., Daniel, H., Toffaletti, D. L., Djordjevic, J. T., et al. (2009) · Infection and Immunity · doi:10.1128/iai.00565-09 · Cited by 105 · see citing works
Djordjevic, J. T. (2010) · Frontiers in Microbiology · doi:10.3389/fmicb.2010.00125 · Cited by 102 · see citing works
Damveld, R. A., Arentshorst, M., Franken, A. C. W., vanKuyk, P., Klis, F. M., van den Hondel, C. A. M. J. J., & Ram, A. F. J. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.04827.x · Cited by 99 · see citing works
Toxoplasma gondii: Perfecting an Intracellular Life Style
Sibley, L. D. (2003) · Traffic · doi:10.1034/j.1600-0854.2003.00117.x · Cited by 98 · see citing works
pH Signaling in Human Fungal Pathogens: a New Target for Antifungal Strategies
Cornet, M., & Gaillardin, C. M. (2014) · Eukaryotic Cell · doi:10.1128/ec.00313-13 · Cited by 99 · see citing works
Hayes, B. M. E., Anderson, M. A., Traven, A., van der Weerden, N. L., & Bleackley, M. R. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1573-8 · Cited by 93 · see citing works
Calcineurin Regulation in Fungi and Beyond
Stie, J., & Fox, D. S. (2007) · Eukaryotic Cell · doi:10.1128/ec.00326-07 · Cited by 89 · see citing works
Self-citationRoles of Calcineurin and Crz1 in Antifungal Susceptibility and Virulence of <i>Candida glabrata</i>
Miyazaki, T., Yamauchi, S., Inamine, T., Nagayoshi, Y., Saijo, T., Izumikawa, K., Seki, M., Kakeya, H., Yamamoto, Y., Yanagihara, K., et al. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01364-09 · Cited by 88 · see citing works
Siafakas, A. R., Sorrell, T. C., Wright, L. C., Wilson, C. F., Larsen, M., Boadle, R. A., Williamson, P. R., & Djordjevic, J. T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707913200 · Cited by 88 · see citing works
Nooney, L., Matthews, R., & Burnie, J. (2005) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2004.08.013 · Cited by 83 · see citing works
Yago, J. I., Lin, C., & Chung, K.-R. (2011) · Molecular Plant Pathology · doi:10.1111/j.1364-3703.2010.00701.x · Cited by 81 · see citing works
Yin, Z., Tang, W., Wang, J., Liu, X., Yang, L., Gao, C., Zhang, J., Zhang, H., Zheng, X., Wang, P., et al. (2015) · Molecular Plant Pathology · doi:10.1111/mpp.12317 · Cited by 80 · see citing works
Olson, G. M., Fox, D. S., Wang, P., Alspaugh, J. A., & Buchanan, K. L. (2006) · Eukaryotic Cell · doi:10.1128/ec.00182-06 · Cited by 80 · see citing works
Self-citationIdentification and Characterization of anSKN7Homologue inCryptococcus neoformans
Wormley, F. L., Heinrich, G., Miller, J. L., Perfect, J. R., & Cox, G. M. (2005) · Infection and Immunity · doi:10.1128/iai.73.8.5022-5030.2005 · Cited by 76 · see citing works
Self-citationFungal kinases and transcription factors regulating brain infection in Cryptococcus neoformans
Lee, K.-T., Hong, J., Lee, D., Lee, M., Cha, S., Lim, Y.-G., Jung, K.-W., Hwangbo, A., Lee, Y., Yu, S.-J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15329-2 · Cited by 76 · see citing works
Baldwin, T. K., Winnenburg, R., Urban, M., Rawlings, C., Koehler, J., & Hammond-Kosack, K. E. (2006) · Molecular Plant-Microbe Interactions · doi:10.1094/mpmi-19-1451 · Cited by 75 · see citing works
Mayer, F. L., & Kronstad, J. W. (2017) · mBio · doi:10.1128/mbio.01537-17 · Cited by 76 · see citing works
Chayakulkeeree, M., Sorrell, T. C., Siafakas, A. R., Wilson, C. F., Pantarat, N., Gerik, K. J., Boadle, R. A., & Djordjevic, J. T. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06310.x · Cited by 72 · see citing works
Kraus, P. R., Nichols, C. B., & Heitman, J. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.6.1079-1087.2005 · Cited by 72 · see citing works
Self-citationMiyazaki, T., Inamine, T., Yamauchi, S., Nagayoshi, Y., Saijo, T., Izumikawa, K., Seki, M., Kakeya, H., Yamamoto, Y., Yanagihara, K., et al. (2010) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2010.00611.x · Cited by 70 · see citing works
Attenuation of echinocandin activity at elevated concentrations: a review of the paradoxical effect
Wiederhold, N. P. (2007) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0b013e3282f1be7f · Cited by 64 · see citing works
Protein-O-mannosyltransferases in virulence and development
Lengeler, K. B., Tielker, D., & Ernst, J. F. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7409-z · Cited by 64 · see citing works
Ngamskulrungroj, P., Price, J. L., Sorrell, T. C., Perfect, J. R., & Meyer, W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016076 · Cited by 63 · see citing works
Yi, S., Sahni, N., Daniels, K. J., Pujol, C., Srikantha, T., & Soll, D. R. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-07-0688 · Cited by 62 · see citing works
Benaducci, T., Sardi, J. D. C. O., Lourencetti, N. M. S., Scorzoni, L., Gullo, F. P., Rossi, S. A., Braz, J. D., Prata, M. C. D. A., Fusco‐Almeida, A. M., & Mendes‐Giannini, M. J. S. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00290 · Cited by 62 · see citing works
Tang, R. J., Breger, J. A., Idnurm, A., Gerik, K. J., Lodge, J. K., Heitman, J., Calderwood, S. B., & Mylonakis, E. E. (2005) · Infection and Immunity · doi:10.1128/iai.73.12.8219-8225.2005 · Cited by 60 · see citing works
Self-citationDudgeon, D. D., Zhang, N., Ositelu, O. O., Kim, H., & Cunningham, K. W. (2008) · Eukaryotic Cell · doi:10.1128/ec.00291-08 · Cited by 59 · see citing works
Glycosyltransferases and their products: cryptococcal variations on fungal themes
Klutts, J. S., Yoneda, A., Reilly, M. C., Bose, I., & Doering, T. L. (2006) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2006.00054.x · Cited by 59 · see citing works
Yin, Y., Wu, S., Chui, C., Ma, T., Jiang, H., Hahn, M., & Ma, Z. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007285 · Cited by 58 · see citing works
Esher, S. K., Ost, K. S., Kohlbrenner, M. A., Pianalto, K. M., Telzrow, C. L., Campuzano, A., Nichols, C. B., Munro, C. A., Wormley, F. L., & Alspaugh, J. A. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007126 · Cited by 54 · see citing works
Yang, D., Jung, K., Bang, S., Lee, J.-W., Song, M.-H., Averette, A. F., Festa, R. A., Ianiri, G., Idnurm, A., Thiele, D. J., et al. (2016) · Genetics · doi:10.1534/genetics.116.190595 · Cited by 56 · see citing works
Self-citationPillai, A. D., Addo, R., Sharma, P., Nguitragool, W., Srinivasan, P., & Desai, S. A. (2013) · Molecular Microbiology · doi:10.1111/mmi.12159 · Cited by 55 · see citing works
The serine/threonine phosphatases of apicomplexan parasites
Yang, C., & Arrizabalaga, G. (2017) · Molecular Microbiology · doi:10.1111/mmi.13715 · Cited by 55 · see citing works
Kmetzsch, L., Staats, C. C., Simon, E., Fonseca, F. L., Oliveira, D. L., Joffe, L. S., Rodrigues, J., Leal, A. L., Nimrichter, L., Rodrigues, M. L., et al. (2010) · Eukaryotic Cell · doi:10.1128/ec.00114-10 · Cited by 52 · see citing works
FPPI: Fusarium graminearum Protein−Protein Interaction Database
Zhao, X., Zhang, X., Tang, W., & Chen, L. (2009) · Journal of Proteome Research · doi:10.1021/pr900415b · Cited by 52 · see citing works
Ren, P., Springer, D. J., Behr, M. J., Samsonoff, W. A., Chaturvedi, S., & Chaturvedi, V. P. (2006) · Eukaryotic Cell · doi:10.1128/ec.00009-06 · Cited by 49 · see citing works
A Molecular and Genomic View of the Fungal Cell Wall
Klis, F. M., Ram, A. F. J., & de Groot, P. W. J. (2007) · Springer eBooks · doi:10.1007/978-3-540-70618-2_4 · Cited by 48 · see citing works
Paradoxical echinocandin activity: a limitedin vitrophenomenon?
Wiederhold, N. P. (2009) · Medical Mycology · doi:10.1080/13693780802428542 · Cited by 48 · see citing works
Lee, H., Lamichhane, A. K., Garraffo, H. M., Kwon-Chung, K. J., & Chang, Y. C. (2012) · Molecular Microbiology · doi:10.1111/j.1365-2958.2012.08016.x · Cited by 47 · see citing works
Fox, D. S., & Heitman, J. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.9.1526-1538.2005 · Cited by 47 · see citing works
Self-citationFox, D. S., Cox, G. M., & Heitman, J. (2003) · Eukaryotic Cell · doi:10.1128/ec.2.5.1025-1035.2003 · Cited by 47 · see citing works
Self-citationPhosphoproteome of Cryptococcus neoformans
Selvan, L. D. N., Renuse, S., Kaviyil, J. E., Sharma, J. N., Pinto, S. M., Yelamanchi, S. D., Puttamallesh, V. N., Ravikumar, R., Pandey, A., Prasad, T. S. K., et al. (2013) · Journal of Proteomics · doi:10.1016/j.jprot.2013.06.029 · Cited by 44 · see citing works
Cao, C., Wang, Y., Husain, S., Soteropoulos, P., & Xue, C. (2019) · mBio · doi:10.1128/mbio.01952-19 · Cited by 45 · see citing works
Mitogen activated protein kinases ofAspergillus fumigatus
May, G. S., Xue, T., Kontoyiannis, D. P., & Gustin, M. C. (2005) · Medical Mycology · doi:10.1080/13693780400024784 · Cited by 45 · see citing works
- Authors
- Kraus, P. R., Fox, D. S., Cox, G. M., & Heitman, J.
- Affiliations
- Duke Medical Center (US)
- Howard Hughes Medical Institute (US)
- ORCID
- Heitman, Joseph
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2003-04-29
- Volume
- 48
- Issue
- 5
- Pages
- 1377-1387
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W1586693095
- Cited by
- 217
- References
- 56
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 9 · 2020: 5 · 2019: 8 · 2018: 11 · 2017: 11 · 2016: 18 · 2015: 7 · 2014: 13 · 2013: 10 · 2012: 6
- FWCI
- 9.35
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases (R37AI039115, P01-AI44975, R01AI042159, R01 AI39115, R01AI42159, P01AI044975, R01 AI50438, R01AI050438, R01AI039115)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- Cryptococcus neoformans, Mpk1, cell integrity pathway, calcineurin, antifungal resistance, nikkomycin Z, caspofungin, FK506, chitin synthase inhibition, cell wall integrity, osmotic stabilization, virulence, cryptococcosis, drug synergy
- MeSH terms
- Animals, Antifungal Agents, Cell Wall, Cryptococcosis, Cryptococcus neoformans, Culture Media, Enzyme Inhibitors, Female, Fungal Proteins, Mice, Inbred DBA, Temperature, Virulence, Gene Expression Regulation, Fungal, Calcineurin, Mitogen-Activated Protein Kinases, Saccharomyces cerevisiae Proteins, Mice, Calcineurin Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review