Calcineurin Is Essential for Virulence in Candida albicans
Open accessAbstract
Calcineurin is a conserved Ca 2+ -calmodulin-activated, serine/threonine-specific protein phosphatase that regulates a variety of physiological processes, e.g., cell cycle progression, polarized growth, and adaptation to salt and alkaline pH stresses. In the pathogenic yeast Cryptococcus neoformans , calcineurin is also essential for growth at 37°C and virulence. To investigate whether calcineurin plays a role in the virulence of Candida albicans , the major fungal pathogen of humans, we constructed C. albicans mutants in which both alleles of the CMP1 gene, encoding the calcineurin catalytic subunit, were deleted. The C. albicans Δ cmp1 mutants displayed hypersensitivity to elevated Na + , Li + , and Mn 2+ concentrations and to alkaline pH, phenotypes that have been described after calcineurin inactivation in the related yeast Saccharomyces cerevisiae . Unlike S. cerevisiae calcineurin mutants, which exhibit reduced susceptibility to high Ca 2+ concentrations, growth of C. albicans was inhibited in the presence of 300 mM CaCl 2 after the deletion of CMP1 , demonstrating that there are also differences in calcineurin-mediated cellular responses between these two yeast species. In contrast to C. neoformans , inactivation of calcineurin did not cause temperature sensitivity in C. albicans . In addition, hyphal growth, an important virulence attribute of C. albicans , was not impaired in the Δ cmp1 mutants under a variety of inducing conditions. Nevertheless, the virulence of the mutants was strongly attenuated in a mouse model of systemic candidiasis, demonstrating that calcineurin signaling is essential for virulence in C. albicans .
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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 [2]
C. albicans calcineurin mutants show hypersensitivity to agents causing cell wall damage or perturbing cell membrane integrity, including some antifungals.
“Also these mutants show hypersensitivity to agents causing cell wall damage or perturbing cell membrane integrity including some antifungals.”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Bader et al. 2003
Calcineurin is essential for C. albicans survival in serum and virulence in a murine model of infection.
“Calcineurin has been shown to be essential for C. albicans survival in serum and virulence in a murine model of infection, but the molecular mechanisms involved are still unknown (Blankenship et al. 2003;Bader et al. 2003;Sanglard et al. 2003).”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Bader et al. 2003
C. albicans mutants lacking either calcineurin subunit are viable but exhibit increased sensitivity to ionic stress conditions.
“C. albicans mutants lacking either one of the calcineurin subunits are viable but exhibit increased sensitivity to ionic stress conditions (Cruz et al. 2002;Sanglard et al. 2003;Bader et al. 2003).”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Bader et al. 2003
The C. albicans cna1/cna1 and cmp1/cmp1 strains, having deleted the calcineurin catalytic subunit, exhibit increased susceptibility to alkaline cation toxicity.
“The C. albicans cna1/cna1 and cmp1/cmp1 strains, having deleted the calcineurin catalytic subunit, exhibit increased susceptibility to alkaline cation toxicity (Sanglard et al. 2003;Bader et al. 2003).”
From Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor (2005) · cites this paper as Bader et al. 2003
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
The mechanism of action of cyclosporin A and FK506
Schreiber, S. L., & Crabtree, G. R. (1992) · Immunology Today · doi:10.1016/0167-5699(92)90111-j · Cited by 2,127 · see citing works
Nonfilamentous C. albicans Mutants Are Avirulent
Lo, H.-J., Köhler, J. R., DiDomenico, B., Loebenberg, D., Cacciapuoti, A., & Fink, G. R. (1997) · Cell · doi:10.1016/s0092-8674(00)80358-x · Cited by 1,809 · see citing works
Isogenic strain construction and gene mapping in Candida albicans.
Fonzi, W. A., & Irwin, M. Y. (1993) · Genetics · doi:10.1093/genetics/134.3.717 · Cited by 1,695 · see citing works
Gillum, A. M., Tsay, E. Y. H., & Kirsch, D. R. (1984) · Molecular and General Genetics MGG · doi:10.1007/bf00328721 · Cited by 1,253 · see citing works
Gimeno, C. J., Ljungdahl, P. O., Styles, C. A., & Fink, G. R. (1992) · Cell · doi:10.1016/0092-8674(92)90079-r · Cited by 1,184 · see citing works
Lee, K. L., BUCKLEY, H. R., & Campbell, C. C. (1975) · Medical Mycology · doi:10.1080/00362177585190271 · Cited by 791 · see citing works
Suppression of Hyphal Formation in Candida albicans by Mutation of a STE12 Homolog
Liu, H., Köhler, J. R., & Fink, G. R. (1994) · Science · doi:10.1126/science.7992058 · Cited by 788 · 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
Stathopoulos, A. M., & Cyert, M. S. (1997) · Genes & Development · doi:10.1101/gad.11.24.3432 · Cited by 442 · see citing works
Cunningham, K. W., & Fink, G. R. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.124.3.351 · Cited by 432 · see citing works
Differential Expression and Function of Two Homologous Subunits of Yeast 1,3-β-D-Glucan Synthase
Mazur, P., Morin, N. R., Baginsky, W. F., El-Sherbeini, M., Clemas, J. A., NIELSEN, J. B. K., & Foor, F. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.10.5671 · Cited by 425 · see citing works
The protein phosphatase calcineurin is essential for NaCl tolerance of Saccharomyces cerevisiae.
Mendoza, I., Rubio, F., Rodriguez-Navarro, A., & Pardo, J. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37038-2 · Cited by 350 · see citing works
Calcineurin is essential for survival during membrane stress in Candida albicans
Cruz, M. C., Goldstein, A. L., Blankenship, J. R., Del Poeta, M., Davis, D., Cardenas, M. E., Perfect, J. R., McCusker, J. H., & Heitman, J. (2002) · The EMBO Journal · doi:10.1093/emboj/21.4.546 · Cited by 342 · cited 2× · see citing works
“albicans calcineurin mutants, which were obtained by deleting the CNB1 gene encoding the regulatory subunit of calcineurin, were hypersensitive to membrane stress caused by the presence of sodium dodecyl sulfate or ergosterol biosynthesis inhibitors (7).”
BackgroundMatheos, D. P., Kingsbury, T. J., Ahsan, U. S., & Cunningham, K. W. (1997) · Genes & Development · doi:10.1101/gad.11.24.3445 · Cited by 332 · see citing works
Leberer, E., Harcus, D., Dignard, D., Johnson, L., Ushinsky, S. C., Thomas, D. Y., & Schröppel, K. (2001) · Molecular Microbiology · doi:10.1046/j.1365-2958.2001.02672.x · Cited by 295 · see citing works
Cyert, M. S., Kunisawa, R., Kaim, D., & Thorner, J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.16.7376 · Cited by 289 · see citing works
Transcription factors in Candida albicans – environmental control of morphogenesis
Ernst, J. F. (2000) · Microbiology · doi:10.1099/00221287-146-8-1763 · Cited by 286 · see citing works
Nakamura, T., Liu, Y., Hirata, D., Namba, H., Harada, S., Hirokawa, T., & Miyakawa, T. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06090.x · Cited by 270 · see citing works
Essential role of calcineurin in response to endoplasmic reticulum stress
Bonilla, M., Nastase, K. K., & Cunningham, K. W. (2002) · The EMBO Journal · doi:10.1093/emboj/21.10.2343 · Cited by 255 · see citing works
Potent Synergism of the Combination of Fluconazole and Cyclosporine in <i>Candida albicans</i>
Marchetti, O., Moreillon, P., Glauser, M. P., Bille, J., & Sanglard, D. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.9.2373-2381.2000 · Cited by 252 · see citing works
Stathopoulos-Gerontides, A., Guo, J. J., & Cyert, M. S. (1999) · Genes & Development · doi:10.1101/gad.13.7.798 · Cited by 240 · see citing works
Cyert, M., & Thorner, J. W. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.8.3460 · Cited by 236 · see citing works
Schweizer, A., Rupp, S., Taylor, B. N., Röllinghoff, M., & Schröppel, K. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.02132.x · Cited by 232 · see citing works
Millon, L., Manteaux, A., Reboux, G., Drobacheff, C., Monod, M., Barale, T., & Michel-Briand, Y. (1994) · Journal of Clinical Microbiology · doi:10.1128/jcm.32.4.1115-1118.1994 · Cited by 205 · see citing works
Serrano, R., Ruiz, A., Bernal, D., Chambers, J. R., & Ariño, J. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.03246.x · Cited by 198 · see citing works
Köhler, G. A., White, T. C., & Agabian, N. (1997) · Journal of Bacteriology · doi:10.1128/jb.179.7.2331-2338.1997 · Cited by 190 · see citing works
Liu, Y., Ishii, S., Tokai, M., Tsutsumi, H., Ohki, O., Akada, R., Tanaka, K., Tsuchiya, E., Fukui, S., & Miyakawa, T. (1991) · Molecular and General Genetics MGG · doi:10.1007/bf00260706 · Cited by 177 · 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
Lay, J., Henry, L. K., Clifford, J., Koltin, Y., Bulawa, C. E., & Becker, J. M. (1998) · Infection and Immunity · doi:10.1128/iai.66.11.5301-5306.1998 · Cited by 174 · see citing works
Virulence genes in the pathogenic yeastCandida albicans
Navarro-García, F., Sánchez, M., Nombela, C., & Plá, J. (2001) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2001.tb00577.x · Cited by 170 · see citing works
Pathogenicity of Candida albicans auxotrophic mutants in experimental infections
Kirsch, D. R., & Whitney, R. R. (1991) · Infection and Immunity · doi:10.1128/iai.59.9.3297-3300.1991 · Cited by 150 · see citing works
Cruz, M. C., Fox, D. S., & Heitman, J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.5.1020 · Cited by 150 · see citing works
Sequential gene disruption in Candida albicans by FLP‐mediated site‐specific recombination
Morschhäuser, J., Michel, S., & Staib, P. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01393.x · Cited by 147 · see citing works
Yeast putative transcription factors involved in salt tolerance
Mendizabal, I., Rios, G., Mulet, J. M., Serrano, R., & de Larrinoa, I. F. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00249-x · Cited by 136 · see citing works
Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains.
Breuder, T., Hemenway, C. S., Movva, N. R., Cardenas, M. E., & Heitman, J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.12.5372 · Cited by 135 · see citing works
Cruz, M. C., Poeta, M. D., Wang, P., Wenger, R. M., Zenke, G., Quesniaux, V. F. J., Movva, N. R., Perfect, J. R., Cardenas, M. E., & Heitman, J. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.1.143-149.2000 · Cited by 129 · see citing works
Sundstrom, P., Cutler, J., & Staab, J. (2002) · Infection and Immunity · doi:10.1128/iai.70.6.3281-3283.2002 · Cited by 128 · see citing works
Prokisch, H., Yarden, O., Dieminger, M., Tropschug, M., & Barthelmess, I. B. (1997) · Molecular and General Genetics MGG · doi:10.1007/s004380050551 · Cited by 125 · see citing works
Antifungal activity in <i>Saccharomyces cerevisiae</i> is modulated by calcium signalling
Edlind, T., Smith, L., Henry, K., Katiyar, S., & Nickels, J. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.03165.x · Cited by 114 · see citing works
Marchetti, O., Entenza, J. M., Sanglard, D., Bille, J., Glauser, M. P., & Moreillon, P. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.11.2932-2938.2000 · Cited by 113 · see citing works
Moser, M. J., Geiser, J. R., & Davis, T. N. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4824 · Cited by 104 · see citing works
Morschhäuser, J., Michel, S., & Hacker, J. (1998) · Molecular and General Genetics MGG · doi:10.1007/s004380050665 · Cited by 101 · see citing works
Growth and guidance of the fungal hypha
Gow, N. A. R. (1994) · Microbiology · doi:10.1099/13500872-140-12-3193 · Cited by 95 · see citing works
cDNA cloning of a calcineurin B homolog in Saccharomyces cerevisiae
Kuno, T., Tanaka, H., Mukai, H., Chang, C., Hiraga, K., Miyakawa, T., & Tanaka, C. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(05)81188-x · Cited by 94 · see citing works
Cyert, M., & Thorner, J. W. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.8.3460-3469.1992 · Cited by 82 · 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
FARCASANU, I. C., Hirata, D., Tsuchiya, E., Nishiyama, F., & Miyakawa, T. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.0712a.x · Cited by 72 · see citing works
Ura-status-dependent adhesion of Candida albicans mutants
Bain, J. M., Stubberfield, C. R., & Gow, N. A. R. (2001) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2001.tb10905.x · Cited by 63 · see citing works
FARCASANU, I. C., Hirata, D., Tsuchiya, E., Nishiyama, F., & Miyakawa, T. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.tb20865.x · Cited by 52 · see citing works
Garc�a, M. G., O'Connor, J.-E., Garc�a, L. L., Irar, S., Herrero, E., & Agudo, L. D. C. (2001) · Yeast · doi:10.1002/1097-0061(20010315)18:4 · Cited by 45 · see citing works
Avirulence of Candida albicans auxotrophic mutants in a rat model of oropharyngeal candidiasis
Cole, M. F., Bowen, W. H., Zhao, X.-J., & Cihlar, R. L. (1995) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1995.tb07413.x · Cited by 35 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
LaFayette, S. L., Collins, C., Zaas, A. K., Schell, W. A., Betancourt-Quiroz, M., Gunatilaka, A. A. L., Perfect, J. R., & Cowen, L. E. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1001069 · Cited by 329 · see citing works
Harnessing 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
Rispail, N., Soanes, D. M., Ant, C., Czajkowski, R., Grünler, A., Huguet, R., Pérez‐Nadales, E., Poli, A., Sartorel, E., Valiante, V., et al. (2009) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2009.01.002 · Cited by 312 · see citing works
An update on antifungal targets and mechanisms of resistance in<i>Candida</i><i>albicans</i>
Akins, R. A. (2005) · Medical Mycology · doi:10.1080/13693780500138971 · Cited by 291 · see citing works
Virulence Factors in Candida species
Staniszewska, M. (2019) · Current Protein and Peptide Science · doi:10.2174/1389203720666190722152415 · Cited by 281 · see citing works
NLLSS: Predicting Synergistic Drug Combinations Based on Semi-supervised Learning
Chen, X., Ren, B., Chen, M., Wang, Q., Zhang, L., & Yan, G. (2016) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004975 · Cited by 281 · see citing works
Calcineurin Controls Growth, Morphology, and Pathogenicity in <i>Aspergillus fumigatus</i>
Steinbach, W. J., Cramer, R. A., Perfect, B. Z., Asfaw, Y. G., Sauer, T. C., Najvar, L. K., Kirkpatrick, W. R., Patterson, T. F., Benjamin, D. K., Heitman, J., et al. (2006) · Eukaryotic Cell · doi:10.1128/ec.00139-06 · Cited by 264 · see citing works
Karkowska‐Kuleta, J., Rąpała‐Kozik, M., & Kozik, A. (2009) · Acta Biochimica Polonica · doi:10.18388/abp.2009_2452 · Cited by 251 · see citing works
<i>CRZ1</i> , a target of the calcineurin pathway in <i>Candida albicans</i>
Karababa, M., Valentino, E., Pardini, G., Coste, A. T., Bille, J., & Sanglard, D. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.05037.x · Cited by 231 · see citing works
Uppuluri, P., Nett, J., Heitman, J., & Andes, D. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01397-07 · Cited by 228 · see citing works
How human pathogenic fungi sense and adapt to pH: the link to virulence
Davis, D. A. (2009) · Current Opinion in Microbiology · doi:10.1016/j.mib.2009.05.006 · Cited by 177 · 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
Cramer, R. A., Perfect, B. Z., Pinchai, N., Park, S., Perlin, D. S., Asfaw, Y. G., Heitman, J., Perfect, J. R., & Steinbach, W. J. (2008) · Eukaryotic Cell · doi:10.1128/ec.00086-08 · Cited by 172 · see citing works
Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans
Cui, J., Ren, B., Tong, Y., Dai, H., & Zhang, L. (2015) · Virulence · doi:10.1080/21505594.2015.1039885 · Cited by 173 · see citing works
Thermotolerance 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
Schumacher, J., Fernandez-de-Larrinoa, Í., & Tudzynski, B. (2008) · Eukaryotic Cell · doi:10.1128/ec.00426-07 · Cited by 155 · see citing works
Onyewu, C., Wormley, F. L., Perfect, J. R., & Heitman, J. (2004) · Infection and Immunity · doi:10.1128/iai.72.12.7330-7333.2004 · Cited by 121 · see citing works
Pardini, G., De Groot, P. W. J., Coste, A. T., Karababa, M., Klis, F. M., de Koster, C. G., & Sanglard, D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606361200 · Cited by 121 · see citing works
Functional characterization of the Aspergillus fumigatus calcineurin
Ferreira, M. E. D. S., Heinekamp, T., Härtl, A., Brakhage, A. A., Semighini, C. P., Harris, S. D., Savoldi, M., de Gouvêa, P. F., Goldman, M. H. D. S., & Goldman, G. H. (2007) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2006.08.004 · Cited by 121 · 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
Calcineurin Is Required forCandida albicansTo Survive Calcium Stress in Serum
Blankenship, J. R., & Heitman, J. (2005) · Infection and Immunity · doi:10.1128/iai.73.9.5767-5774.2005 · Cited by 111 · see citing works
Calcineurin controls drug tolerance, hyphal growth, and virulence in Candida dubliniensis
Chen, Y.-L., Brand, A., Morrison, E. L., Silao, F. G. S., Bigol, U. G., Malbas, F. F., Nett, J. E., Andes, D. R., Solis, N. V., Filler, S. G., et al. (2011) · Eukaryotic Cell · doi:10.1128/ec.00310-10 · Cited by 107 · see citing works
Okoli, I. G., Coleman, J. J., Tempakakis, E., An, W. F., Holson, E. B., Wagner, F. F., Conery, A. L., Larkins‐Ford, J., Wu, G., Stern, A., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007025 · Cited by 107 · see citing works
Animal models: an important tool in mycology
Capilla, J., Clemons, K. V., & Stevens, D. A. (2007) · Medical Mycology · doi:10.1080/13693780701644140 · Cited by 94 · 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
Roles 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
Drug Resistance and Novel Therapeutic Approaches in Invasive Candidiasis
Murphy, S. E., & Bicanic, T. A. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.759408 · Cited by 85 · see citing works
Bader, T., Schröppel, K., Bentink, S., Agabian, N., Köhler, G., & Morschhäuser, J. (2006) · Infection and Immunity · doi:10.1128/iai.00142-06 · Cited by 81 · see citing works
Self-citationJuvvadi, P. R., Fortwendel, J. R., Rogg, L. E., Burns, K. A., Randell, S. H., & Steinbach, W. J. (2011) · Molecular Microbiology · doi:10.1111/j.1365-2958.2011.07886.x · Cited by 80 · see citing works
Santos, M., & de Larrinoa, I. F. (2005) · Current Genetics · doi:10.1007/s00294-005-0003-8 · Cited by 78 · see citing works
Reedy, J. L., Filler, S. G., & Heitman, J. (2010) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2009.09.002 · Cited by 76 · see citing works
Silkworm as an experimental animal for research on fungal infections
Matsumoto, Y., & Sekimizu, K. (2019) · Microbiology and Immunology · doi:10.1111/1348-0421.12668 · Cited by 77 · see citing works
Kim, S., Hu, J., Oh, Y., Park, J., Choi, J., Lee, Y., Dean, R. A., & Mitchell, T. K. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000909 · Cited by 72 · see citing works
Hameed, S., Dhamgaye, S., Singh, A., Goswami, S. K., & Prasad, R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018684 · Cited by 69 · see citing works
Heath, V. L., Shaw, S. L., Roy, S., & Cyert, M. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.3.695-704.2004 · Cited by 68 · see citing works
Hanaoka, N., Takano, Y., Shibuya, K., Fugo, H., Uehara, Y., & Niimi, M. (2008) · Eukaryotic Cell · doi:10.1128/ec.00129-08 · Cited by 67 · see citing works
Anticandidal Effect and Mechanisms of Monoterpenoid, Perillyl Alcohol against Candida albicans
Ansari, M. A., Fatima, Z., & Hameed, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162465 · Cited by 66 · see citing works
Epp, E., Vanier, G., Harcus, D., Lee, A. Y., Jansen, G., Hallett, M., Sheppard, D. C., Thomas, D. Y., Munro, C. A., Mullick, A., et al. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000753 · Cited by 61 · see citing works
Genome-wide functional analysis of phosphatases in the pathogenic fungus Cryptococcus neoformans
Jin, J., Lee, K.-T., Hong, J., Lee, D., Jang, E.-H., Kim, J. Y., Lee, Y., Lee, S., So, Y.-S., Jung, K., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18028-0 · Cited by 57 · see citing works
Fan, W., Idnurm, A., Breger, J., Mylonakis, E., & Heitman, J. (2007) · Infection and Immunity · doi:10.1128/iai.01977-06 · Cited by 57 · see citing works
Vandeputte, P., Ischer, F., Sanglard, D., & Coste, A. T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026962 · Cited by 56 · see citing works
Li, F., Wang, Z., Zhang, L.-B., Ying, S., & Feng, M. (2014) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-014-6124-6 · Cited by 53 · see citing works
Genomics, molecular targets and the discovery of antifungal drugs
Odds, F. C. (2005) · Revista Iberoamericana de Micología · doi:10.1016/s1130-1406(05)70048-6 · Cited by 52 · see citing works
Singh, N., & Heitman, J. (2004) · Transplantation · doi:10.1097/01.tp.0000117252.75651.d6 · Cited by 50 · see citing works
Calcium-calcineurin signaling pathway in Candida albicans: A potential drug target
Li, W., Shrivastava, M., Lu, H., & Jiang, Y. (2021) · Microbiological Research · doi:10.1016/j.micres.2021.126786 · Cited by 47 · see citing works
Variability of the Stripe Rust Pathogen
Wan, A., Wang, X., Kang, Z., & Chen, X. (2017) · Springer eBooks · doi:10.1007/978-94-024-1111-9_2 · Cited by 47 · see citing works
Zhang, H., Guo, J., Voegele, R. T., Zhang, J., Duan, Y., Luo, H., & Kang, Z. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049262 · Cited by 46 · see citing works
Harren, K., Schumacher, J., & Tudzynski, B. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041761 · Cited by 46 · see citing works
Cao, Y., Du, M., Luo, S., & Xia, Y. (2014) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-014-5876-3 · Cited by 43 · see citing works
Progress and prospects for targeting Hsp90 to treat fungal infections
Veri, A. O., & Cowen, L. E. (2014) · Parasitology · doi:10.1017/s0031182013002072 · Cited by 43 · see citing works
Heitman, J. (2005) · Science · doi:10.1126/science.1119321 · Cited by 42 · see citing works
Chen, S. C.-A., Lewis, R. E., & Kontoyiannis, D. P. (2011) · Virulence · doi:10.4161/viru.2.4.16764 · Cited by 41 · see citing works
Sircaik, S., Román, E., Bapat, P., Lee, K. K., Andes, D. R., Gow, N. A. R., Nobile, C. J., Pla, J., & Panwar, S. L. (2021) · Cellular Microbiology · doi:10.1111/cmi.13307 · Cited by 41 · see citing works
On the Roles of Calcineurin in Fungal Growth and Pathogenesis
Chen, Y., Kozubowski, L., Cardenas, M. E., & Heitman, J. (2010) · Current Fungal Infection Reports · doi:10.1007/s12281-010-0027-5 · Cited by 39 · see citing works
Innate Immune and Fungal Model of Alzheimer’s Disease
Parady, B. (2018) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-180073 · Cited by 39 · see citing works
Roles of Cch1 and Mid1 in Morphogenesis, Oxidative Stress Response and Virulence in Candida albicans
Yu, Q., Wang, H., Cheng, X., Xu, N., Ding, X., Xing, L., & Li, M. (2012) · Mycopathologia · doi:10.1007/s11046-012-9569-0 · Cited by 38 · see citing works
Delattin, N., Brucker, K. D., Craik, D. J., Cheneval, O., Fröhlich, M., Veber, M., Girandon, L., Davis, T. R., Weeks, A. E., Kumamoto, C. A., et al. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01274-13 · Cited by 37 · see citing works
Bairwa, G., Rasheed, M., Taigwal, R., Sahoo, R., & Kaur, R. (2014) · Biochemical Journal · doi:10.1042/bj20130757 · Cited by 36 · see citing works
Calcineurin-Mediated Regulation of Hyphal Growth, Septation, and Virulence in Aspergillus fumigatus
Juvvadi, P. R., Lamoth, F., & Steinbach, W. J. (2014) · Mycopathologia · doi:10.1007/s11046-014-9794-9 · Cited by 36 · see citing works
Onyewu, C., Afshari, N. A., & Heitman, J. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00393-06 · Cited by 36 · see citing works
Huang, S., He, Z., Zhang, S., Keyhani, N. O., Song, Y., Yang, Z., Jiang, Y., Zhang, W., Pei, Y., & Zhang, Y. (2015) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2015.08.009 · Cited by 35 · see citing works
Signaling cascades as drug targets in model and pathogenic fungi.
Bastidas, R. J., Reedy, J. L., Morales-Johansson, H., Heitman, J., & Cardenas, M. E. (2008) · PubMed · Cited by 34 · see citing works
Latgé, J., & Calderone, R. (2006) · Springer eBooks · doi:10.1007/3-540-28135-5_5 · Cited by 33 · see citing works
Fu, C., Donadio, N., Cardenas, M. E., & Heitman, J. (2017) · Genetics · doi:10.1534/genetics.117.300422 · Cited by 33 · see citing works
Immunotherapy of Fungal Infections
Datta, K., & Hamad, M. A. (2015) · Immunological Investigations · doi:10.3109/08820139.2015.1093913 · Cited by 33 · see citing works
Cervantes-Chávez, J. A., Ali, S., & Bakkeren, G. (2011) · Molecular Plant-Microbe Interactions · doi:10.1094/mpmi-09-10-0202 · Cited by 32 · see citing works
Denardi, L. B., Mario, D. A. N., Loreto, É. S., Santúrio, J. M., & Alves, S. H. (2015) · Brazilian Journal of Microbiology · doi:10.1590/s1517-838246120120442 · Cited by 32 · see citing works
Zinc Cluster Transcription Factors Alter Virulence in Candida albicans
Issi, L., Farrer, R. A., Pastor, K., Landry, B. D., Delorey, T. M., Bell, G. W., Thompson, D. A., Cuomo, C. A., & Rao, R. P. (2016) · Genetics · doi:10.1534/genetics.116.195024 · Cited by 31 · see citing works
Calcineurin: The Achilles’ heel of fungal pathogens
Yadav, V., & Heitman, J. (2023) · PLoS Pathogens · doi:10.1371/journal.ppat.1011445 · Cited by 29 · see citing works
Cha, H., Won, D., Kang, S., Kim, E.-S., Lee, K.-A., Lee, W.-J., Lee, K.-T., & Bahn, Y.-S. (2025) · PLOS Pathogens · doi:10.1371/journal.ppat.1013363 · Cited by 24 · see citing works
Novel Regulatory Mechanisms of Pathogenicity and Virulence to Combat MDR inCandida albicans
Hameed, S., & Fatima, Z. (2013) · International Journal of Microbiology · doi:10.1155/2013/240209 · Cited by 24 · see citing works
Calcineurin-dependent contributions to fitness in the opportunistic pathogen <i>Candida glabrata</i>
Pavesic, M. W., Gale, A. N., Nickels, T. J., Harrington, A. A., Bussey, M., & Cunningham, K. W. (2024) · mSphere · doi:10.1128/msphere.00554-23 · Cited by 22 · see citing works
Lipidome analysis reveals antifungal polyphenol curcumin affects membrane lipid homeostasis
Sharma, M. (2011) · Frontiers in Bioscience-Elite · doi:10.2741/451 · Cited by 22 · see citing works
Jia, Y., Tang, R.-J., Wang, L., Zhang, X., Wang, Y., Jia, X.-M., & Jiang, Y.-Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048369 · Cited by 19 · see citing works
Cha, H., Won, D., & Bahn, Y.-S. (2025) · mBio · doi:10.1128/mbio.02475-23 · Cited by 19 · see citing works
Molecular Principles of Antifungal Drug Resistance
Sanglard, D., & White, T. C. (2014) · ASM Press eBooks · doi:10.1128/9781555815776.ch14 · Cited by 19 · see citing works
Thomas, E., Sircaik, S., Román, E., Brunel, J. M., Johri, A. K., Plá, J., & Panwar, S. L. (2015) · FEMS Yeast Research · doi:10.1093/femsyr/fov095 · Cited by 18 · see citing works
Reedy, J. L., Husain, S., Ison, M. G., Pruett, T. L., Singh, N., & Heitman, J. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.50.4.1573-1577.2006 · Cited by 18 · see citing works
Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans
Jung, W. H., Son, Y.-E., Oh, S., Fu, C., Kim, H., Kwak, J., Cardenas, M. E., Heitman, J., & Park, H.-S. (2017) · G3 Genes Genomes Genetics · doi:10.1534/g3.117.300444 · Cited by 17 · see citing works
Li, W., Zhang, Z., Luo, Y., Liang, N., Pi, X., & Fan, Y. (2020) · Journal of Medical Microbiology · doi:10.1099/jmm.0.001161 · Cited by 17 · see citing works
Development of Non-Immunosuppressive FK506 Derivatives as Antifungal and Neurotrophic Agents
Jung, J. A., & Yoon, Y. J. (2020) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.1911.11008 · Cited by 14 · see citing works
Ppg1, a PP2A-Type Protein Phosphatase, Controls Filament Extension and Virulence in Candida albicans
Bataineh, M. T. A., Lazzell, A. L., Lopez-Ribot, J. L., & Kadosh, D. (2014) · Eukaryotic Cell · doi:10.1128/ec.00199-14 · Cited by 16 · see citing works
Malik, A., Afaq, S., El-Gamal, B., Ellatif, M. E. A., Hassan, W. N., Dera, A. A., Noor, R., & Tarique, M. (2019) · Bioinformation · doi:10.6026/97320630015277 · Cited by 14 · see citing works
Loss, O., Bertuzzi, M., Yan, Y., Fedorova, N. D., McCann, B. L., Armstrong-James, D. P. H., Espeso, E. A., Read, N. D., Nierman, W. C., & Bignell, E. (2017) · Molecular Microbiology · doi:10.1111/mmi.13840 · Cited by 13 · see citing works
Cek1 regulates ß(1,3)-glucan exposure through calcineurin effectors in Candida albicans
Wagner, A. S., Lumsdaine, S. W., Mangrum, M. M., King, A. E., Hancock, T. J., Sparer, T. E., & Reynolds, T. B. (2022) · PLOS Genetics · doi:10.1371/journal.pgen.1010405 · Cited by 12 · see citing works
Antifungal Targets, Mechanisms of Action, and Resistance in Candida albicans
Akins, R. A., & Sobel, J. D. (2009) · Humana Press eBooks · doi:10.1007/978-1-59745-180-2_29 · Cited by 12 · see citing works
Wong, S. S. W., Raşid, O., Laskaris, P., Fekkar, A., Cavaillon, J., Steinbach, W. J., & Ibrahim-Granet, O. (2017) · Virulence · doi:10.1080/21505594.2017.1339007 · Cited by 11 · see citing works
Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans
Son, Y.-E., Fu, C., Jung, W. H., Oh, S., Kwak, J., Cardenas, M. E., Heitman, J., & Park, H.-S. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00355 · Cited by 11 · see citing works
The putative flavin carrier family FlcA-C is important forAspergillus fumigatusvirulence
de Castro, P. A., Chiaratto, J., Morais, E. R., dos Reis, T. F., Mitchell, T. K., Brown, N. A., & Goldman, G. H. (2016) · Virulence · doi:10.1080/21505594.2016.1239010 · Cited by 10 · see citing works
Thewes, S., Krohn, S., Schmith, A., Herzog, S., Stach, T., Weissenmayer, B. A., & Mutzel, R. (2012) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2012.07.006 · Cited by 10 · see citing works
Thewes, S., Schubert, S. K., Park, K., & Mutzel, R. (2013) · Journal of Basic Microbiology · doi:10.1002/jobm.201200574 · Cited by 9 · see citing works
Tang, H., Ren, J., Yuan, J., Zeng, B., & Wei, H. (2010) · African Journal of Microbiology Research · Cited by 9 · see citing works
Briñez-Ortega, E., de Almeida, V. L., Lopes, J. C. D., & Burgos, A. E. (2020) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765202020181323 · Cited by 9 · see citing works
Antifungal Targets, Mechanisms of Action, and Resistance in Candida albicans
Akins, R. A., & Sobel, J. D. (2017) · Springer eBooks · doi:10.1007/978-3-319-46718-4_30 · Cited by 9 · see citing works
Silencing the crowd: high‐throughput functional genomics inMagnaporthe oryzae
Caracuel‐Rios, Z., & Talbot, N. J. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06257.x · Cited by 9 · see citing works
Liu, C., Liu, T., Lv, Z., Qin, M., Qu, Z., Zhang, Z., Li, F., Chen, D., Zhang, X., Chen, X., et al. (2022) · Frontiers in Plant Science · doi:10.3389/fpls.2022.925645 · Cited by 8 · see citing works
Fungal calcineurin complex as an antifungal target: From past to present to future
Li, X., Zhang, C., & Lü, L. (2022) · Fungal Biology Reviews · doi:10.1016/j.fbr.2022.10.003 · Cited by 7 · see citing works
Resheat-Eini, Z., Zelter, A., Gorovits, R., Read, N. D., & Yarden, O. (2008) · Fungal Genetics Reports · doi:10.4148/1941-4765.1088 · Cited by 7 · see citing works
Aequorin as a Useful Calcium-Sensing Reporter in Candida albicans
Sanglard, D. (2021) · Journal of Fungi · doi:10.3390/jof7040319 · Cited by 6 · see citing works
Iron Acquisition in the Pathobiology of Candida albicans
Srivastav, M. K., Nair, R., & Natarajan, K. (2017) · Springer eBooks · doi:10.1007/978-3-319-50409-4_17 · Cited by 5 · see citing works
- Authors
- Bader, T., Bodendorfer, B., Schröppel, K., & Morschhäuser, J.
- Affiliations
- University of Würzburg (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Universität Erlangen, D-91054 Erlangen
- Institut für Molekulare Infektionsbiologie, Universität Würzburg, D-97070 Würzburg
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2003-09
- Volume
- 71
- Issue
- 9
- Pages
- 5344-5354
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC187310
- OpenAlex
- W2149198831
- Cited by
- 121
- References
- 52
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 1 · 2017: 8 · 2016: 5 · 2015: 6 · 2014: 9 · 2013: 5 · 2012: 5
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Infection and Immunity (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Burroughs Wellcome Fund
- Deutsche Forschungsgemeinschaft
- Bayerische Forschungsstiftung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- calcineurin, Candida albicans, virulence, systemic candidiasis, hyphal growth, cation sensitivity, temperature sensitivity, protein phosphatase, mouse model, Cryptococcus neoformans
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Candida albicans, Candidiasis, DNA, Fungal, Female, Genes, Fungal, Humans, Hydrogen-Ion Concentration, Mice, Inbred BALB C, Molecular Sequence Data, Virulence, Gene Deletion, Sequence Homology, Amino Acid, Calcineurin, Protein Subunits, Mice
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