메뉴 건너뛰기




Volumn 11, Issue 6, 2008, Pages 511-516

Fungal adaptation to the mammalian host: it is a new world, after all

Author keywords

[No Author keywords available]

Indexed keywords

CARBON DIOXIDE; FUNGAL PROTEIN; GLYOXYLIC ACID; ISOCITRATE LYASE; OXYGEN; SIDEROPHORE;

EID: 56949096142     PISSN: 13695274     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mib.2008.09.018     Document Type: Review
Times cited : (61)

References (50)
  • 1
    • 0033653838 scopus 로고    scopus 로고
    • Signal transduction cascades regulating pseudohyphal differentiation of Saccharomyces cerevisiae
    • Pan X., Harashima T., and Heitman J. Signal transduction cascades regulating pseudohyphal differentiation of Saccharomyces cerevisiae. Curr Opin Microbiol 3 (2000) 567-572
    • (2000) Curr Opin Microbiol , vol.3 , pp. 567-572
    • Pan, X.1    Harashima, T.2    Heitman, J.3
  • 2
    • 33846622349 scopus 로고    scopus 로고
    • A Ras1-Cdc24 signal transduction pathway mediates thermotolerance in the fungal pathogen Cryptococcus neoformans
    • Nichols C.B., Perfect Z.H., and Alspaugh J.A. A Ras1-Cdc24 signal transduction pathway mediates thermotolerance in the fungal pathogen Cryptococcus neoformans. Mol Microbiol 63 (2007) 1118-1130
    • (2007) Mol Microbiol , vol.63 , pp. 1118-1130
    • Nichols, C.B.1    Perfect, Z.H.2    Alspaugh, J.A.3
  • 3
    • 38849141080 scopus 로고    scopus 로고
    • Transcriptional profile of ras1 and ras2 and the potential role of farnesylation in the dimorphism of the human pathogen Paracoccidioides brasiliensis
    • Fernandes L., Paes H.C., Tavares A.H., Silva S.S., Dantas A., Soares C.M., Torres F.A., and Felipe M.S. Transcriptional profile of ras1 and ras2 and the potential role of farnesylation in the dimorphism of the human pathogen Paracoccidioides brasiliensis. FEMS Yeast Res 8 (2008) 300-310
    • (2008) FEMS Yeast Res , vol.8 , pp. 300-310
    • Fernandes, L.1    Paes, H.C.2    Tavares, A.H.3    Silva, S.S.4    Dantas, A.5    Soares, C.M.6    Torres, F.A.7    Felipe, M.S.8
  • 4
    • 37349024997 scopus 로고    scopus 로고
    • A p21-activated kinase is required for conidial germination in Penicillium marneffei
    • This work identifies a downstream effector of the Ras1 signaling pathway as a novel regulator of temperature-dependent transcriptional and developmental changes in a thermally dimorphic fungus.
    • Boyce K.J., and Andrianopoulos A. A p21-activated kinase is required for conidial germination in Penicillium marneffei. PLoS Pathog 3 (2007) e162. This work identifies a downstream effector of the Ras1 signaling pathway as a novel regulator of temperature-dependent transcriptional and developmental changes in a thermally dimorphic fungus.
    • (2007) PLoS Pathog , vol.3
    • Boyce, K.J.1    Andrianopoulos, A.2
  • 5
    • 33646253928 scopus 로고    scopus 로고
    • Global control of dimorphism and virulence in fungi
    • Nemecek J.C., Wuthrich M., and Klein B.S. Global control of dimorphism and virulence in fungi. Science 312 (2006) 583-588
    • (2006) Science , vol.312 , pp. 583-588
    • Nemecek, J.C.1    Wuthrich, M.2    Klein, B.S.3
  • 6
    • 34548654789 scopus 로고    scopus 로고
    • Dimorphism and virulence in fungi
    • Klein B.S., and Tebbets B. Dimorphism and virulence in fungi. Curr Opin Microbiol 10 (2007) 314-319
    • (2007) Curr Opin Microbiol , vol.10 , pp. 314-319
    • Klein, B.S.1    Tebbets, B.2
  • 7
    • 42449127140 scopus 로고    scopus 로고
    • Temperature-induced switch to the pathogenic yeast form of Histoplasma capsulatum requires Ryp1, a conserved transcriptional regulator
    • This work identifies a global transcriptional regulator that is required for morphogenesis and expression of yeast phase-specific genes in a dimorphic fungal pathogen.
    • Nguyen V.Q., and Sil A. Temperature-induced switch to the pathogenic yeast form of Histoplasma capsulatum requires Ryp1, a conserved transcriptional regulator. Proc Natl Acad Sci U S A 105 (2008) 4880-4885. This work identifies a global transcriptional regulator that is required for morphogenesis and expression of yeast phase-specific genes in a dimorphic fungal pathogen.
    • (2008) Proc Natl Acad Sci U S A , vol.105 , pp. 4880-4885
    • Nguyen, V.Q.1    Sil, A.2
  • 8
    • 0035811478 scopus 로고    scopus 로고
    • The glyoxylate cycle is required for fungal virulence
    • Lorenz M.C., and Fink G.R. The glyoxylate cycle is required for fungal virulence. Nature 412 (2001) 83-86
    • (2001) Nature , vol.412 , pp. 83-86
    • Lorenz, M.C.1    Fink, G.R.2
  • 9
    • 33646343945 scopus 로고    scopus 로고
    • Niche-specific regulation of central metabolic pathways in a fungal pathogen
    • This work reveals distinct patterns of expression for glyoxylate cycle genes in different micro-environments within the host of a fungal pathogen.
    • Barelle C.J., Priest C.L., Maccallum D.M., Gow N.A., Odds F.C., and Brown A.J. Niche-specific regulation of central metabolic pathways in a fungal pathogen. Cell Microbiol 8 (2006) 961-971. This work reveals distinct patterns of expression for glyoxylate cycle genes in different micro-environments within the host of a fungal pathogen.
    • (2006) Cell Microbiol , vol.8 , pp. 961-971
    • Barelle, C.J.1    Priest, C.L.2    Maccallum, D.M.3    Gow, N.A.4    Odds, F.C.5    Brown, A.J.6
  • 10
    • 33847194205 scopus 로고    scopus 로고
    • Mutations in alternative carbon utilization pathways in Candida albicans attenuate virulence and confer pleiotropic phenotypes
    • Ramirez M.A., and Lorenz M.C. Mutations in alternative carbon utilization pathways in Candida albicans attenuate virulence and confer pleiotropic phenotypes. Eukaryot Cell 6 (2007) 280-290
    • (2007) Eukaryot Cell , vol.6 , pp. 280-290
    • Ramirez, M.A.1    Lorenz, M.C.2
  • 11
    • 40649109347 scopus 로고    scopus 로고
    • Upregulation of glyoxylate cycle genes upon Paracoccidioides brasiliensis internalization by murine macrophages and in vitro nutritional stress condition
    • Derengowski L.S., Tavares A.H., Silva S., Procopio L.S., Felipe M.S., and Silva-Pereira I. Upregulation of glyoxylate cycle genes upon Paracoccidioides brasiliensis internalization by murine macrophages and in vitro nutritional stress condition. Med Mycol 46 (2008) 125-134
    • (2008) Med Mycol , vol.46 , pp. 125-134
    • Derengowski, L.S.1    Tavares, A.H.2    Silva, S.3    Procopio, L.S.4    Felipe, M.S.5    Silva-Pereira, I.6
  • 12
    • 0031259678 scopus 로고    scopus 로고
    • Molecular characterization of mutants of the acetate regulatory gene facB of Aspergillus nidulans
    • Todd R.B., Kelly J.M., Davis M.A., and Hynes M.J. Molecular characterization of mutants of the acetate regulatory gene facB of Aspergillus nidulans. Fungal Genet Biol 22 (1997) 92-102
    • (1997) Fungal Genet Biol , vol.22 , pp. 92-102
    • Todd, R.B.1    Kelly, J.M.2    Davis, M.A.3    Hynes, M.J.4
  • 13
    • 33751375138 scopus 로고    scopus 로고
    • Developmental regulation of the glyoxylate cycle in the human pathogen Penicillium marneffei
    • Canovas D., and Andrianopoulos A. Developmental regulation of the glyoxylate cycle in the human pathogen Penicillium marneffei. Mol Microbiol 62 (2006) 1725-1738
    • (2006) Mol Microbiol , vol.62 , pp. 1725-1738
    • Canovas, D.1    Andrianopoulos, A.2
  • 14
    • 33646575320 scopus 로고    scopus 로고
    • Analysis of the regulation, expression, and localisation of the isocitrate lyase from Aspergillus fumigatus, a potential target for antifungal drug development
    • Ebel F., Schwienbacher M., Beyer J., Heesemann J., Brakhage A.A., and Brock M. Analysis of the regulation, expression, and localisation of the isocitrate lyase from Aspergillus fumigatus, a potential target for antifungal drug development. Fungal Genet Biol 43 (2006) 476-489
    • (2006) Fungal Genet Biol , vol.43 , pp. 476-489
    • Ebel, F.1    Schwienbacher, M.2    Beyer, J.3    Heesemann, J.4    Brakhage, A.A.5    Brock, M.6
  • 15
    • 33847709957 scopus 로고    scopus 로고
    • Aspergillus fumigatus does not require fatty acid metabolism via isocitrate lyase for development of invasive aspergillosis
    • Schobel F., Ibrahim-Granet O., Ave P., Latge J.P., Brakhage A.A., and Brock M. Aspergillus fumigatus does not require fatty acid metabolism via isocitrate lyase for development of invasive aspergillosis. Infect Immun 75 (2007) 1237-1244
    • (2007) Infect Immun , vol.75 , pp. 1237-1244
    • Schobel, F.1    Ibrahim-Granet, O.2    Ave, P.3    Latge, J.P.4    Brakhage, A.A.5    Brock, M.6
  • 16
    • 36048935085 scopus 로고    scopus 로고
    • Ability to grow on lipids accounts for the fully virulent phenotype in neutropenic mice of Aspergillus fumigatus null mutants in the key glyoxylate cycle enzymes
    • Olivas I., Royuela M., Romero B., Monteiro M.C., Minguez J.M., Laborda F., and De Lucas J.R. Ability to grow on lipids accounts for the fully virulent phenotype in neutropenic mice of Aspergillus fumigatus null mutants in the key glyoxylate cycle enzymes. Fungal Genet Biol 45 (2008) 45-60
    • (2008) Fungal Genet Biol , vol.45 , pp. 45-60
    • Olivas, I.1    Royuela, M.2    Romero, B.3    Monteiro, M.C.4    Minguez, J.M.5    Laborda, F.6    De Lucas, J.R.7
  • 17
    • 50349097380 scopus 로고    scopus 로고
    • Genes differentially expressed in conidia and hyphae of Aspergillus fumigatus upon exposure to human neutrophils
    • This work uses a microarray to identify carbon utilization genes as a major component of the transcriptional response of a fungal pathogen to host cells.
    • Sugui J.A., Kim H.S., Zarember K.A., Chang Y.C., Gallin J.I., Nierman W.C., and Kwon-Chung K.J. Genes differentially expressed in conidia and hyphae of Aspergillus fumigatus upon exposure to human neutrophils. PLoS ONE 3 (2008) e2655. This work uses a microarray to identify carbon utilization genes as a major component of the transcriptional response of a fungal pathogen to host cells.
    • (2008) PLoS ONE , vol.3
    • Sugui, J.A.1    Kim, H.S.2    Zarember, K.A.3    Chang, Y.C.4    Gallin, J.I.5    Nierman, W.C.6    Kwon-Chung, K.J.7
  • 18
    • 51849144248 scopus 로고    scopus 로고
    • Siderophores in fungal physiology and virulence
    • Haas H., Eisendle M., and Turgeon B.G. Siderophores in fungal physiology and virulence. Annu Rev Phytopathol 46 (2008) 149-187
    • (2008) Annu Rev Phytopathol , vol.46 , pp. 149-187
    • Haas, H.1    Eisendle, M.2    Turgeon, B.G.3
  • 19
    • 43049121756 scopus 로고    scopus 로고
    • Histoplasma requires SID1, a member of an iron-regulated siderophore gene cluster, for host colonization
    • Hwang L.H., Mayfield J.A., Rine J., and Sil A. Histoplasma requires SID1, a member of an iron-regulated siderophore gene cluster, for host colonization. PLoS Pathog 4 (2008) e1000044
    • (2008) PLoS Pathog , vol.4
    • Hwang, L.H.1    Mayfield, J.A.2    Rine, J.3    Sil, A.4
  • 20
    • 46849120759 scopus 로고    scopus 로고
    • Sre1, an iron-modulated GATA DNA-binding protein of iron-uptake genes in the fungal pathogen Histoplasma capsulatum
    • Chao L.Y., Marletta M.A., and Rine J. Sre1, an iron-modulated GATA DNA-binding protein of iron-uptake genes in the fungal pathogen Histoplasma capsulatum. Biochemistry 47 (2008) 7274-7283
    • (2008) Biochemistry , vol.47 , pp. 7274-7283
    • Chao, L.Y.1    Marletta, M.A.2    Rine, J.3
  • 23
    • 47049127797 scopus 로고    scopus 로고
    • Candida albicans ferric reductases are differentially regulated in response to distinct forms of iron limitation by the Rim101 and CBF transcription factors
    • Baek Y.U., Li M., and Davis D.A. Candida albicans ferric reductases are differentially regulated in response to distinct forms of iron limitation by the Rim101 and CBF transcription factors. Eukaryot Cell 7 (2008) 1168-1179
    • (2008) Eukaryot Cell , vol.7 , pp. 1168-1179
    • Baek, Y.U.1    Li, M.2    Davis, D.A.3
  • 24
    • 45149086178 scopus 로고    scopus 로고
    • An endocytic mechanism for haemoglobin-iron acquisition in Candida albicans
    • This paper identifies a novel pathway by which a fungal pathogen acquires iron from host hemoglobin.
    • Weissman Z., Shemer R., Conibear E., and Kornitzer D. An endocytic mechanism for haemoglobin-iron acquisition in Candida albicans. Mol Microbiol 69 (2008) 201-217. This paper identifies a novel pathway by which a fungal pathogen acquires iron from host hemoglobin.
    • (2008) Mol Microbiol , vol.69 , pp. 201-217
    • Weissman, Z.1    Shemer, R.2    Conibear, E.3    Kornitzer, D.4
  • 27
    • 0033796715 scopus 로고    scopus 로고
    • Candida albicans RIM101 pH response pathway is required for host-pathogen interactions
    • Davis D., Edwards Jr. J.E., Mitchell A.P., and Ibrahim A.S. Candida albicans RIM101 pH response pathway is required for host-pathogen interactions. Infect Immun 68 (2000) 5953-5959
    • (2000) Infect Immun , vol.68 , pp. 5953-5959
    • Davis, D.1    Edwards Jr., J.E.2    Mitchell, A.P.3    Ibrahim, A.S.4
  • 30
    • 34548567025 scopus 로고    scopus 로고
    • PalC, one of two Bro1 domain proteins in the fungal pH signalling pathway, localizes to cortical structures and binds Vps32
    • This work is the first to investigate the role of PalC in the fungal pH signaling cascade and identifies this protein as a potential bridge between the plasma membrane and endosomal signaling complexes.
    • Galindo A., Hervas-Aguilar A., Rodriguez-Galan O., Vincent O., Arst Jr. H.N., Tilburn J., and Penalva M.A. PalC, one of two Bro1 domain proteins in the fungal pH signalling pathway, localizes to cortical structures and binds Vps32. Traffic 8 (2007) 1346-1364. This work is the first to investigate the role of PalC in the fungal pH signaling cascade and identifies this protein as a potential bridge between the plasma membrane and endosomal signaling complexes.
    • (2007) Traffic , vol.8 , pp. 1346-1364
    • Galindo, A.1    Hervas-Aguilar, A.2    Rodriguez-Galan, O.3    Vincent, O.4    Arst Jr., H.N.5    Tilburn, J.6    Penalva, M.A.7
  • 31
    • 28444473460 scopus 로고    scopus 로고
    • Deletions of endocytic components VPS28 and VPS32 affect growth at alkaline pH and virulence through both RIM101-dependent and RIM101-independent pathways in Candida albicans
    • Cornet M., Bidard F., Schwarz P., Da Costa G., Blanchin-Roland S., Dromer F., and Gaillardin C. Deletions of endocytic components VPS28 and VPS32 affect growth at alkaline pH and virulence through both RIM101-dependent and RIM101-independent pathways in Candida albicans. Infect Immun 73 (2005) 7977-7987
    • (2005) Infect Immun , vol.73 , pp. 7977-7987
    • Cornet, M.1    Bidard, F.2    Schwarz, P.3    Da Costa, G.4    Blanchin-Roland, S.5    Dromer, F.6    Gaillardin, C.7
  • 32
    • 36849012447 scopus 로고    scopus 로고
    • Evidence for the direct involvement of the proteasome in the proteolytic processing of the Aspergillus nidulans zinc finger transcription factor PacC
    • Hervas-Aguilar A., Rodriguez J.M., Tilburn J., Arst Jr. H.N., and Penalva M.A. Evidence for the direct involvement of the proteasome in the proteolytic processing of the Aspergillus nidulans zinc finger transcription factor PacC. J Biol Chem 282 (2007) 34735-34747
    • (2007) J Biol Chem , vol.282 , pp. 34735-34747
    • Hervas-Aguilar, A.1    Rodriguez, J.M.2    Tilburn, J.3    Arst Jr., H.N.4    Penalva, M.A.5
  • 33
    • 9244246998 scopus 로고    scopus 로고
    • Biosynthesis and uptake of siderophores is controlled by the PacC-mediated ambient-pH regulatory system in Aspergillus nidulans
    • Eisendle M., Oberegger H., Buttinger R., Illmer P., and Haas H. Biosynthesis and uptake of siderophores is controlled by the PacC-mediated ambient-pH regulatory system in Aspergillus nidulans. Eukaryot Cell 3 (2004) 561-563
    • (2004) Eukaryot Cell , vol.3 , pp. 561-563
    • Eisendle, M.1    Oberegger, H.2    Buttinger, R.3    Illmer, P.4    Haas, H.5
  • 34
    • 34248370072 scopus 로고    scopus 로고
    • Mucosal tissue invasion by Candida albicans is associated with E-cadherin degradation, mediated by transcription factor Rim101p and protease Sap5p
    • Villar C.C., Kashleva H., Nobile C.J., Mitchell A.P., and Dongari-Bagtzoglou A. Mucosal tissue invasion by Candida albicans is associated with E-cadherin degradation, mediated by transcription factor Rim101p and protease Sap5p. Infect Immun 75 (2007) 2126-2135
    • (2007) Infect Immun , vol.75 , pp. 2126-2135
    • Villar, C.C.1    Kashleva, H.2    Nobile, C.J.3    Mitchell, A.P.4    Dongari-Bagtzoglou, A.5
  • 38
    • 27844610829 scopus 로고    scopus 로고
    • 2 sensing during Cryptococcus neoformans growth, differentiation, and virulence
    • 2 sensing during Cryptococcus neoformans growth, differentiation, and virulence. Curr Biol 15 (2005) 2013-2020
    • (2005) Curr Biol , vol.15 , pp. 2013-2020
    • Bahn, Y.S.1    Cox, G.M.2    Perfect, J.R.3    Heitman, J.4
  • 40
    • 35748930845 scopus 로고    scopus 로고
    • Differential regulation of the transcriptional repressor NRG1 accounts for altered host-cell interactions in Candida albicans and Candida dubliniensis
    • This work demonstrates that cAMP-dependent filamentation in response to host-specific cues plays a major role in the virulence of different Candida species.
    • Moran G.P., MacCallum D.M., Spiering M.J., Coleman D.C., and Sullivan D.J. Differential regulation of the transcriptional repressor NRG1 accounts for altered host-cell interactions in Candida albicans and Candida dubliniensis. Mol Microbiol 66 (2007) 915-929. This work demonstrates that cAMP-dependent filamentation in response to host-specific cues plays a major role in the virulence of different Candida species.
    • (2007) Mol Microbiol , vol.66 , pp. 915-929
    • Moran, G.P.1    MacCallum, D.M.2    Spiering, M.J.3    Coleman, D.C.4    Sullivan, D.J.5
  • 41
    • 33845659996 scopus 로고    scopus 로고
    • Candida albicans transcription factor Ace2 regulates metabolism and is required for filamentation in hypoxic conditions
    • Mulhern S.M., Logue M.E., and Butler G. Candida albicans transcription factor Ace2 regulates metabolism and is required for filamentation in hypoxic conditions. Eukaryot Cell 5 (2006) 2001-2013
    • (2006) Eukaryot Cell , vol.5 , pp. 2001-2013
    • Mulhern, S.M.1    Logue, M.E.2    Butler, G.3
  • 42
    • 33746363517 scopus 로고    scopus 로고
    • Transcriptional response of Candida albicans to hypoxia: linkage of oxygen sensing and Efg1p-regulatory networks
    • Setiadi E.R., Doedt T., Cottier F., Noffz C., and Ernst J.F. Transcriptional response of Candida albicans to hypoxia: linkage of oxygen sensing and Efg1p-regulatory networks. J Mol Biol 361 (2006) 399-411
    • (2006) J Mol Biol , vol.361 , pp. 399-411
    • Setiadi, E.R.1    Doedt, T.2    Cottier, F.3    Noffz, C.4    Ernst, J.F.5
  • 44
    • 33847335459 scopus 로고    scopus 로고
    • A link between virulence and homeostatic responses to hypoxia during infection by the human fungal pathogen Cryptococcus neoformans
    • This paper formally identifies the hypoxia response and two of its regulators as essential for virulence of a fungal pathogen.
    • Chun C.D., Liu O.W., and Madhani H.D. A link between virulence and homeostatic responses to hypoxia during infection by the human fungal pathogen Cryptococcus neoformans. PLoS Pathog 3 (2007) e22. This paper formally identifies the hypoxia response and two of its regulators as essential for virulence of a fungal pathogen.
    • (2007) PLoS Pathog , vol.3
    • Chun, C.D.1    Liu, O.W.2    Madhani, H.D.3
  • 45
    • 34247547435 scopus 로고    scopus 로고
    • Sre1p, a regulator of oxygen sensing and sterol homeostasis, is required for virulence in Cryptococcus neoformans
    • Chang Y.C., Bien C.M., Lee H., Espenshade P.J., and Kwon-Chung K.J. Sre1p, a regulator of oxygen sensing and sterol homeostasis, is required for virulence in Cryptococcus neoformans. Mol Microbiol 64 (2007) 614-629
    • (2007) Mol Microbiol , vol.64 , pp. 614-629
    • Chang, Y.C.1    Bien, C.M.2    Lee, H.3    Espenshade, P.J.4    Kwon-Chung, K.J.5
  • 46
    • 0028350193 scopus 로고
    • Chloroquine induces human macrophage killing of Histoplasma capsulatum by limiting the availability of intracellular iron and is therapeutic in a murine model of histoplasmosis
    • Newman S.L., Gootee L., Brunner G., and Deepe Jr. G.S. Chloroquine induces human macrophage killing of Histoplasma capsulatum by limiting the availability of intracellular iron and is therapeutic in a murine model of histoplasmosis. J Clin Invest 93 (1994) 1422-1429
    • (1994) J Clin Invest , vol.93 , pp. 1422-1429
    • Newman, S.L.1    Gootee, L.2    Brunner, G.3    Deepe Jr., G.S.4
  • 47
    • 0030824696 scopus 로고    scopus 로고
    • Chloroquine induces human mononuclear phagocytes to inhibit and kill Cryptococcus neoformans by a mechanism independent of iron deprivation
    • Levitz S.M., Harrison T.S., Tabuni A., and Liu X. Chloroquine induces human mononuclear phagocytes to inhibit and kill Cryptococcus neoformans by a mechanism independent of iron deprivation. J Clin Invest 100 (1997) 1640-1646
    • (1997) J Clin Invest , vol.100 , pp. 1640-1646
    • Levitz, S.M.1    Harrison, T.S.2    Tabuni, A.3    Liu, X.4
  • 49
    • 33745116230 scopus 로고    scopus 로고
    • Chloroquine inhibits Paracoccidioides brasiliensis survival within human monocytes by limiting the availability of intracellular iron
    • Dias-Melicio L.A., Moreira A.P., Calvi S.A., and Soares A.M. Chloroquine inhibits Paracoccidioides brasiliensis survival within human monocytes by limiting the availability of intracellular iron. Microbiol Immunol 50 (2006) 307-314
    • (2006) Microbiol Immunol , vol.50 , pp. 307-314
    • Dias-Melicio, L.A.1    Moreira, A.P.2    Calvi, S.A.3    Soares, A.M.4


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.