Heat Shock Protein 90 Is Required for Conidiation and Cell Wall Integrity in Aspergillus fumigatus
Open accessAbstract
Heat shock protein 90 (Hsp90) is a eukaryotic molecular chaperone. Its involvement in the resistance of Candida albicans to azole and echinocandin antifungals is well established. However, little is known about Hsp90's function in the filamentous fungal pathogen Aspergillus fumigatus . We investigated the role of Hsp90 in A. fumigatus by genetic repression and examined its cellular localization under various stress conditions. Failure to generate a deletion strain of hsp90 suggested that it is essential. Genetic repression of Hsp90 was achieved by an inducible nitrogen-dependent promoter ( pniiA -Hsp90) and led to decreased spore viability, decreased hyphal growth, and severe defects in germination and conidiation concomitant with the downregulation of the conidiation-specific transcription factors brlA , wetA , and abaA . Hsp90 repression potentiated the effect of cell wall inhibitors affecting the β-glucan structure of the cell wall (caspofungin, Congo red) and of the calcineurin inhibitor FK506, supporting a role in regulating cell wall integrity pathways. Moreover, compromising Hsp90 abolished the paradoxical effect of caspofungin. Pharmacological inhibition of Hsp90 by geldanamycin and its derivatives (17-AAG and 17-DMAG) resulted in similar effects. C-terminal green fluorescent protein (GFP) tagging of Hsp90 revealed mainly cytosolic distribution under standard growth conditions. However, treatment with caspofungin resulted in Hsp90 accumulation at the cell wall and at sites of septum formation, further highlighting its role in cell wall stress compensatory mechanisms. Targeting Hsp90 with fungal-specific inhibitors to cripple stress response compensatory pathways represents an attractive new antifungal strategy.
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?
Calcineurin inhibitors (FK506 and cyclosporine) and Hsp90 inhibitors (geldanamycin, 17-AAG, and 17-DMAG) are active against A. fumigatus and potentiate the effect of caspofungin.
“Calcineurin inhibitors (FK506 and cyclosporine) and Hsp90 inhibitors (geldanamycin, 17-allylamino-17-demethoxygeldanamycin [17-AAG], and 17-demethylaminoethylamino-17-demethoxygeldanamycin [17-DMAG]) are active against A. fumigatus and potentiate the effect of caspofungin (6–8)”
From Identification of a Key Lysine Residue in Heat Shock Protein 90 Required for Azole and Echinocandin Resistance in Aspergillus fumigatus (2014) · cites this paper as [7]
Compromising Hsp90-mediated stress responses by genetic modifications of the hsp90 promoter potentiates the effect of caspofungin and abolishes the paradoxical effect of this drug.
“Compromising Hsp90-mediated stress responses by genetic modifications of the hsp90 promoter also potentiated the effect of caspofungin and abolished the paradoxical effect of this drug (7, 12).”
From Identification of a Key Lysine Residue in Heat Shock Protein 90 Required for Azole and Echinocandin Resistance in Aspergillus fumigatus (2014) · cites this paper as [7]
The K27A-K271A double mutation's phenotypic characteristics were similar to those obtained after genetic repression of Hsp90.
“These phenotypic characteristics were similar to those obtained after genetic repression of Hsp90 (7, 12).”
From Identification of a Key Lysine Residue in Heat Shock Protein 90 Required for Azole and Echinocandin Resistance in Aspergillus fumigatus (2014) · cites this paper as [7]
Deletion of rpdA (a class 1 KDAC) was lethal in A. nidulans.
“Interestingly, deletion of rpdA (a class 1 KDAC), whose contribution to KDAC activity is less important, was lethal in A. nidulans, and its repression resulted in growth and conidiation defects that were comparable to the phenotypic consequences of Hsp90 repression in our previous works (7, 12, 41).”
From Identification of a Key Lysine Residue in Heat Shock Protein 90 Required for Azole and Echinocandin Resistance in Aspergillus fumigatus (2014) · cites this paper as [7]
Differences regarding susceptibility to azoles were observed following Hsp90 repression in A. fumigatus and C. albicans.
“Differences regarding susceptibility to azoles were also observed following Hsp90 repression in A. fumigatus and C. albicans (6, 7, 10, 12).”
From Identification of a Key Lysine Residue in Heat Shock Protein 90 Required for Azole and Echinocandin Resistance in Aspergillus fumigatus (2014) · cites this paper as [7]
Repression of rpdA resulted in growth and conidiation defects comparable to the phenotypic consequences of Hsp90 repression.
“Interestingly, deletion of rpdA (a class 1 KDAC), whose contribution to KDAC activity is less important, was lethal in A. nidulans, and its repression resulted in growth and conidiation defects that were comparable to the phenotypic consequences of Hsp90 repression in our previous works (7, 12, 41).”
From Identification of a Key Lysine Residue in Heat Shock Protein 90 Required for Azole and Echinocandin Resistance in Aspergillus fumigatus (2014) · cites this paper as [7]
In Aspergillus fumigatus, Hsp90 is involved in drug resistance, conidiation, and maintenance of cell wall integrity.
“In Aspergillus fumigatus, the role of Hsp90 in drug resistance [16], conidiation and maintenance of cell wall integrity has been well established [17].”
From Heat shock protein 90 localizes to the surface and augments virulence factors of Cryptococcus neoformans (2017) · cites this paper as [17]
Under Hsp90 repression in A. fumigatus, conidiation-specific transcription factors brlA and wetA are down-regulated.
“Supporting these observations, there was down-regulation of the conidiation-specific transcription factors brlA, wetA under Hsp90 repression (Lamoth et al., 2012).”
From Calcineurin as a multifunctional regulator: Unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis (2014) · cites this paper as Lamoth et al., 2012
In A. fumigatus, genetic or pharmacologic inhibition of Hsp90 or calcineurin did not or only modestly impact azole susceptibility.
“Genetic or pharmacologic inhibition of Hsp90 or calcineurin did not (or only modestly) impact azole susceptibility (Lamoth et al., 2012; Lamoth et al., 2013a; Steinbach et al., 2004a).”
From Calcineurin as a multifunctional regulator: Unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis (2014) · cites this paper as Lamoth et al., 2012
In A. fumigatus, Hsp90 is abundantly distributed in the cytosol under standard growth conditions, moves to the nucleus under heat stress, and moves to the cell wall, septa, and hyphal tips in response to caspofungin-induced cell wall stress.
“Subcellular localization analysis of A. fumigatus Hsp90 using an EGFP-tagged strain showed that Hsp90 was abundantly distributed within the cytosol under standard growth conditions and moved to the nucleus under heat stress or to the cell wall, septa and hyphal tips in response to the cell wall stress induced by caspofungin (Lamoth et al., 2012).”
From Calcineurin as a multifunctional regulator: Unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis (2014) · cites this paper as Lamoth et al., 2012
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
National Committee for Clinical Laboratory Standards
Bruck, E. (1980) · PEDIATRICS · doi:10.1542/peds.65.1.187 · Cited by 14,736 · see citing works
Global analysis of protein localization in budding yeast
Huh, W.-K., Falvo, J. V., Gerke, L. C., Carroll, A. S., Howson, R. W., Weissman, J. S., & O'Shea, E. K. (2003) · Nature · doi:10.1038/nature02026 · Cited by 4,248 · see citing works
HSP90 and the chaperoning of cancer
Whitesell, L., & Lindquist, S. L. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1716 · Cited by 2,502 · see citing works
Synergy, antagonism, and what the chequerboard puts between them
Odds, F. C. (2003) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkg301 · Cited by 2,498 · see citing works
Targeting the dynamic HSP90 complex in cancer
Trepel, J. B., Mollapour, M., Giaccone, G., & Neckers, L. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2887 · Cited by 1,523 · see citing works
Colot, H. V., Park, G., Turner, G., Ringelberg, C. S., Crew, C. M., Litvinkova, L., Weiss, R. L., Borkovich, K. A., & Dunlap, J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601456103 · Cited by 1,112 · see citing works
Zhao, R., Davey, M., Hsu, Y.-C., Kaplanek, P., Tong, A., Parsons, A. B., Krogan, N., Cagney, G., Mai, D., Greenblatt, J., et al. (2005) · Cell · doi:10.1016/j.cell.2004.12.024 · Cited by 819 · see citing works
Asexual Sporulation inAspergillus nidulans
Adams, T. H., Wieser, J. K., & Yu, J. (1998) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.62.1.35-54.1998 · Cited by 712 · see citing works
Hsp90 Potentiates the Rapid Evolution of New Traits: Drug Resistance in Diverse Fungi
Cowen, L. E., & Lindquist, S. (2005) · Science · doi:10.1126/science.1118370 · Cited by 698 · see citing works
NLStradamus: a simple Hidden Markov Model for nuclear localization signal prediction
Ba, A. N. N., Pogoutse, A. K., Provart, N. J., & Moses, A. M. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-202 · Cited by 697 · see citing works
Borkovich, K. A., Farrelly, F. W., Finkelstein, D. B., Taulien, J., & Lindquist, S. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.9.3919 · Cited by 641 · see citing works
Cowen, L. E., Singh, S. D., Köhler, J. R., Collins, C., Zaas, A. K., Schell, W. A., Aziz, H., Mylonakis, E., Perfect, J. R., Whitesell, L., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813394106 · Cited by 413 · see citing works
da Silva Ferreira, M. E., Kress, M. R. V. Z., Savoldi, M., Goldman, M. H. S., Härtl, A., Heinekamp, T., Brakhage, A. A., & Goldman, G. H. (2006) · Eukaryotic Cell · doi:10.1128/ec.5.1.207-211.2006 · Cited by 403 · see citing works
Hsp90 Governs Echinocandin Resistance in the Pathogenic Yeast Candida albicans via Calcineurin
Singh, S. D., Robbins, N., Zaas, A. K., Schell, W. A., Perfect, J. R., & Cowen, L. E. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000532 · Cited by 362 · cited 2× · see citing works
“albicans and resulted in increased susceptibility to azoles and echinocandins in vitro and in a murine model of invasive candidiasis (8, 9, 31).”
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
Hsp90 Orchestrates Temperature-Dependent Candida albicans Morphogenesis via Ras1-PKA Signaling
Shapiro, R. S., Uppuluri, P., Zaas, A. K., Collins, C., Senn, H., Perfect, J. R., Heitman, J., & Cowen, L. E. (2009) · Current Biology · doi:10.1016/j.cub.2009.03.017 · Cited by 311 · see citing works
The evolution of fungal drug resistance: modulating the trajectory from genotype to phenotype.
Cowen, L. E. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1835 · Cited by 311 · see citing works
Hsp90 Governs Dispersion and Drug Resistance of Fungal Biofilms
Robbins, N., Uppuluri, P., Nett, J., Rajendran, R., Ramage, G., Lopez-Ribot, J. L., Andes, D., & Cowen, L. E. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002257 · Cited by 291 · 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
Self-citationBorkovich, K. A., Farrelly, F. W., FINKELSTEIN, D. B., et al. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.9.3919-3930.1989 · Cited by 255 · see citing works
Essential Gene Identification and Drug Target Prioritization in Aspergillus fumigatus
Hu, W., Sillaots, S., Lemieux, S., Davison, J., Kauffman, S., Breton, A., Linteau, A., Xin, C., Bowman, J., Becker, J., et al. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030024 · Cited by 237 · see citing works
Fortwendel, J. R., Juvvadi, P. R., Pinchai, N., Perfect, B. Z., Alspaugh, J. A., Perfect, J. R., & Steinbach, W. J. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01154-08 · Cited by 161 · see citing works
Self-citationGenetic Architecture of Hsp90-Dependent Drug Resistance
Cowen, L. E., Carpenter, A. E., Matangkasombut, O., Fink, G. R., & Lindquist, S. (2006) · Eukaryotic Cell · doi:10.1128/ec.00274-06 · Cited by 159 · 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
Fortwendel, J. R., Juvvadi, P. R., Perfect, B. Z., Rogg, L. E., Perfect, J. R., & Steinbach, W. J. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00854-09 · Cited by 153 · see citing works
Self-citationThe GATA factor AreA is essential for chromatin remodelling in a eukaryotic bidirectional promoter
Muro‐Pastor, M. I., Gonzalez, R., Strauss, J., Narendja, F. M., & Scazzocchio, C. (1999) · The EMBO Journal · doi:10.1093/emboj/18.6.1584 · Cited by 151 · see citing works
In Vitro Interactions between Antifungals and Immunosuppressants against Aspergillus fumigatus
Steinbach, W. J., Schell, W. A., Blankenship, J. R., Onyewu, C., Heitman, J., & Perfect, J. R. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.5.1664-1669.2004 · Cited by 135 · see citing works
Self-citationAbaA and WetA govern distinct stages of Aspergillus fumigatus development
Tao, L., & Yu, J.-H. (2011) · Microbiology · doi:10.1099/mic.0.044271-0 · Cited by 133 · see citing works
Hsp90 orchestrates stress response signaling governing fungal drug resistance
Cowen, L. E. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000471 · Cited by 130 · see citing works
Role of HSP90 in salt stress tolerance via stabilization and regulation of calcineurin.
Imai, J., & Yahara, I. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.24.9262-9270.2000 · Cited by 123 · see citing works
Steinbach, W. J., Cramer, R. A., Perfect, B. Z., Henn, C., Nielsen, K., Heitman, J., & Perfect, J. R. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01394-06 · Cited by 108 · see citing works
Self-citationOsherov, N. (2001) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/48.1.75 · Cited by 96 · see citing works
Juvvadi, 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
Self-citationLangfelder, K., Philippe, B., Jahn, B., Latgé, J., & Brakhage, A. A. (2001) · Infection and Immunity · doi:10.1128/iai.69.10.6411-6418.2001 · Cited by 79 · see citing works
Senn, H., Shapiro, R. S., & Cowen, L. E. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-08-0729 · Cited by 67 · 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
Association of ergot alkaloids with conidiation in Aspergillus fumigatus
Coyle, C. M., Kenaley, S. C., Rittenour, W. R., & Panaccione, D. G. (2007) · Mycologia · doi:10.3852/mycologia.99.6.804 · Cited by 56 · see citing works
Tapia, H., & Morano, K. A. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-05-0376 · Cited by 50 · see citing works
Juvvadi, P. R., Fortwendel, J. R., Pinchai, N., Perfect, B. Z., Heitman, J., & Steinbach, W. J. (2008) · Eukaryotic Cell · doi:10.1128/ec.00200-08 · Cited by 42 · see citing works
Self-citationAspergillus fumigatus Calcipressin CbpA Is Involved in Hyphal Growth and Calcium Homeostasis
Pinchai, N., Perfect, B. Z., Juvvadi, P. R., Fortwendel, J. R., Cramer, R. A., Asfaw, Y. G., Heitman, J., Perfect, J. R., & Steinbach, W. J. (2009) · Eukaryotic Cell · doi:10.1128/ec.00336-08 · Cited by 41 · see citing works
Self-citationAssociation of ergot alkaloids with conidiation inAspergillus fumigatus
Coyle, C. M., Kenaley, S. C., Rittenour, W. R., & Panaccione, D. G. (2007) · Mycologia · doi:10.1080/15572536.2007.11832512 · Cited by 26 · see citing works
Thompson, S., Croft, N. J., Sotiriou, A., Piggins, H. D., & Crosthwaite, S. K. (2008) · Eukaryotic Cell · doi:10.1128/ec.00427-07 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Antifungal Drug Resistance: Molecular Mechanisms in <i>Candida albicans</i> and Beyond
Lee, Y., Puumala, E., Robbins, N., & Cowen, L. E. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00199 · Cited by 801 · see citing works
Paulussen, C., Hallsworth, J. E., Álvarez‐Pérez, S., Nierman, W. C., Hamill, P. G., Blain, D., Rediers, H., & Lievens, B. (2016) · Microbial Biotechnology · doi:10.1111/1751-7915.12367 · Cited by 345 · see citing works
Antifungal Drugs: The Current Armamentarium and Development of New Agents
Robbins, N., Wright, G. D., & Cowen, L. E. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.funk-0002-2016 · Cited by 271 · see citing works
Role of Heat-Shock Proteins in Cellular Function and in the Biology of Fungi
Tiwari, S., Thakur, R., & Shankar, J. (2015) · Biotechnology Research International · doi:10.1155/2015/132635 · Cited by 255 · see citing works
Combinatorial strategies for combating invasive fungal infections
Spitzer, M., Robbins, N., & Wright, G. D. (2016) · Virulence · doi:10.1080/21505594.2016.1196300 · Cited by 218 · see citing works
Valiante, V., Macheleidt, J., Föge, M., & Brakhage, A. A. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00325 · Cited by 184 · see citing works
Dermatophyte Resistance to Antifungal Drugs: Mechanisms and Prospectus
Martinez-Rossi, N. M., Bitencourt, T. A., Peres, N. T. A., Lang, E. A. S., Gomes, E. V., Quaresemin, N. R., Martins, M. P., Lopes, L. R., & Rossi, A. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01108 · Cited by 189 · see citing works
Triazole Resistance in Aspergillus spp.: A Worldwide Problem?
Rivero-Menendez, O., Alastruey-Izquierdo, A., Mellado, E., & Cuenca-Estrella, M. (2016) · Journal of Fungi · doi:10.3390/jof2030021 · Cited by 142 · see citing works
Heat shock proteins in infection
Bolhassani, A., & Agi, E. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.08.015 · Cited by 140 · see citing works
Kim, S. H., Iyer, K. R., Pardeshi, L., Muñoz, J. F., Robbins, N., Cuomo, C. A., Wong, K. H., & Cowen, L. E. (2019) · mBio · doi:10.1128/mbio.02529-18 · Cited by 136 · see citing works
Echinocandins for the treatment of invasive aspergillosis: from laboratory to bedside
Aruanno, M., Glampedakis, E., & Lamoth, F. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00399-19 · Cited by 136 · see citing works
Self-citationLeach, M. D., Budge, S., Walker, L. A., Munro, C. A., Cowen, L. E., & Brown, A. J. P. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1003069 · Cited by 133 · see citing works
Molecular Mechanisms of Conidial Germination in Aspergillus spp
Baltussen, T. J. H., Zoll, J., Verweij, P. E., & Melchers, W. J. G. (2019) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00049-19 · Cited by 129 · 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
Self-citationThe fungal Achilles’ heel: targeting Hsp90 to cripple fungal pathogens
Cowen, L. E. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2013.03.005 · Cited by 93 · see citing works
Opportunistic yeast pathogens: reservoirs, virulence mechanisms, and therapeutic strategies
Polvi, E. J., Li, X., O’Meara, T. R., Leach, M. D., & Cowen, L. E. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1860-z · Cited by 90 · see citing works
Lamoth, F., Juvvadi, P. R., Gehrke, C., & Steinbach, W. J. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01857-12 · Cited by 88 · see citing works
Self-citationHagiwara, D., Sakamoto, K., Abe, K., & Gomi, K. (2016) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2016.1162085 · Cited by 87 · see citing works
The contribution of Aspergillus fumigatus stress responses to virulence and antifungal resistance
Brown, N. A., & Goldman, G. H. (2016) · The Journal of Microbiology · doi:10.1007/s12275-016-5510-4 · Cited by 77 · see citing works
Recent advances in the understanding of the Aspergillus fumigatus cell wall
Lee, M. J., & Sheppard, D. C. (2016) · The Journal of Microbiology · doi:10.1007/s12275-016-6045-4 · Cited by 75 · see citing works
Ries, L. N. A., Rocha, M. C., de Castro, P. A., Silva-Rocha, R., Silva, R. N., Freitas, F. Z., de Assis, L. J., Bertolini, M. C., Malavazi, I., & Goldman, G. H. (2017) · mBio · doi:10.1128/mbio.00705-17 · Cited by 76 · see citing works
Regulatory role of the 90-kDa-heat-shock protein (Hsp90) and associated factors on gene expression
Erlejman, A. G., Lagadari, M., Toneatto, J., Piwien‐Pilipuk, G., & Galigniana, M. D. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2013.12.006 · Cited by 74 · see citing works
Lamoth, F., Juvvadi, P. R., Soderblom, E. J., Moseley, M. A., Asfaw, Y. G., & Steinbach, W. J. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02286-13 · Cited by 74 · see citing works
Self-citationRecent Insights into the Paradoxical Effect of Echinocandins
Wagener, J., & Loiko, V. (2017) · Journal of Fungi · doi:10.3390/jof4010005 · Cited by 73 · see citing works
Aspergillus terreus: Novel lessons learned on amphotericin B resistance
Posch, W., Blatzer, M., Wilflingseder, D., & Lass‐Flörl, C. (2018) · Medical Mycology · doi:10.1093/mmy/myx119 · Cited by 74 · see citing works
Developmental regulators in Aspergillus fumigatus
Park, H.-S., & Yu, J. (2016) · The Journal of Microbiology · doi:10.1007/s12275-016-5619-5 · Cited by 71 · see citing works
Boral, H., Metin, B., Döğen, A., Seyedmousavi, S., & İlkit, M. (2017) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2017.10.008 · Cited by 71 · see citing works
Combination Therapy to Treat Fungal Biofilm-Based Infections
Tits, J., Cammue, B. P. A., & Thevissen, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228873 · Cited by 70 · see citing works
Cordeiro, R. D. A., Evangelista, A. J. D. J., Serpa, R., Marques, F. J. D. F., Melo, C. V. S. D., Oliveira, J. S. D., Franco, J. D. S., Alencar, L. P. D., Bandeira, T. D. J. P. G., Brilhante, R. S. N., et al. (2016) · Microbiology · doi:10.1099/mic.0.000222 · Cited by 63 · see citing works
Lamoth, F., Juvvadi, P. R., Gehrke, C., Asfaw, Y. G., & Steinbach, W. J. (2014) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit530 · Cited by 62 · see citing works
Self-citationdos Reis, T. F., de Castro, P. A., Bastos, R. W., Pinzan, C. F., Souza, P. F. N., Ackloo, S. Z., Hossain, M. A., Drewry, D. H., Alkhazraji, S., Ibrahim, A. S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37573-y · Cited by 62 · see citing works
Leach, M. D., & Cowen, L. E. (2014) · Eukaryotic Cell · doi:10.1128/ec.00138-14 · Cited by 62 · see citing works
Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis
Lamoth, F., Juvvadi, P. R., & Steinbach, W. J. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00096 · Cited by 61 · see citing works
Self-citationChatterjee, S., & Tatu, U. (2017) · PLOS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0005836 · Cited by 57 · see citing works
Heat shock protein 90 (Hsp90): A novel antifungal target against Aspergillus fumigatus
Lamoth, F., Juvvadi, P. R., & Steinbach, W. J. (2014) · Critical Reviews in Microbiology · doi:10.3109/1040841x.2014.947239 · Cited by 57 · see citing works
Self-citationSurviving the Heat of the Moment: A Fungal Pathogens Perspective
Leach, M. D., & Cowen, L. E. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003163 · Cited by 55 · see citing works
Bui, D., Lee, Y., Lim, J. Y., Fu, M., Kim, J.-C., Choi, G. J., Son, H., & Lee, Y. (2016) · Scientific Reports · doi:10.1038/srep28154 · Cited by 57 · see citing works
Innate and Adaptive Immune Response to Fungal Products and Allergens
Williams, P. B., Barnes, C. S., Portnoy, J. M., Barnes, C., Baxi, S., Grimes, C., Horner, W. E., Kennedy, K., Larenas‐Linnemann, D. E., Levetin, E., et al. (2016) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2015.11.016 · Cited by 53 · see citing works
Blatzer, M., Blum, G., Jukic, E., Posch, W., Gruber, P., Nagl, M., Binder, U., Maurer, E., Sarg, B., Lindner, H. H., et al. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.05164-14 · Cited by 52 · see citing works
Loiko, V., & Wagener, J. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01690-16 · Cited by 51 · see citing works
Antifungal resistance in Aspergillus terreus: A current scenario
Vahedi‐Shahandashti, R., & Lass‐Flörl, C. (2019) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2019.103247 · Cited by 51 · see citing works
O'Meara, T. R., & Cowen, L. E. (2014) · Cellular Microbiology · doi:10.1111/cmi.12266 · Cited by 48 · see citing works
Roles of Hsp90 in Candida albicans morphogenesis and virulence
Robbins, N., & Cowen, L. E. (2023) · Current Opinion in Microbiology · doi:10.1016/j.mib.2023.102351 · Cited by 50 · see citing works
Animal Models of Aspergillosis.
Désoubeaux, G., & Cray, C. (2018) · Europe PMC (PubMed Central) · Cited by 47 · see citing works
Fabri, J. H. T. M., Rocha, M. C., Fernandes, C. M., Persinoti, G. F., Ries, L. N. A., da Cunha, A. F., Goldman, G. H., Poeta, M. D., & Malavazi, I. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.656548 · Cited by 48 · see citing works
Iurlaro, A., Caroli, M. D., Sabella, E., Pascali, M. D., Rampino, P., Bellis, L. D., Perrotta, C., Dalessandro, G., Piro, G., Fry, S. C., et al. (2016) · Frontiers in Plant Science · doi:10.3389/fpls.2016.01686 · Cited by 43 · see citing works
Vargas-Muñiz, J. M., Renshaw, H., Richards, A. D., Lamoth, F., Soderblom, E. J., Moseley, M. A., Juvvadi, P. R., & Steinbach, W. J. (2015) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2015.05.014 · Cited by 43 · see citing works
Self-citationPotential Microbiological Effects of Higher Dosing of Echinocandins
Steinbach, W. J., Lamoth, F., & Juvvadi, P. R. (2015) · Clinical Infectious Diseases · doi:10.1093/cid/civ725 · Cited by 42 · see citing works
Self-citationMount, H. O., Revie, N. M., Todd, R. T., Anstett, K., Collins, C., Costanzo, M., Boone, C., Robbins, N., Selmecki, A., & Cowen, L. E. (2018) · PLOS Genetics · doi:10.1371/journal.pgen.1007319 · Cited by 34 · see citing works
Tiwari, S., Thakur, R., Goel, G., & Shankar, J. (2016) · Mycopathologia · doi:10.1007/s11046-016-0056-x · Cited by 40 · see citing works
Rocha, M. C., Minari, K., Fabri, J. H. T. M., Kerkaert, J. D., Gava, L. M., da Cunha, A. F., Cramer, R. A., Borges, J. C., & Malavazi, I. (2020) · Cellular Microbiology · doi:10.1111/cmi.13273 · Cited by 39 · see citing works
Small heat shock proteins (HSP12, HSP20 and HSP30) play a role inUstilago maydispathogenesis
Ghosh, A. S. (2014) · FEMS Microbiology Letters · doi:10.1111/1574-6968.12605 · Cited by 36 · see citing works
Heat shock proteins and the calcineurin-crz1 signaling regulate stress responses in fungi
Roy, A., & Tamuli, R. (2022) · Archives of Microbiology · doi:10.1007/s00203-022-02833-w · Cited by 36 · see citing works
Gaziano, R., Campione, E., Iacovelli, F., Marino, D., Pica, F., Francesco, P. D., Aquaro, S., Menichini, F., Falconi, M., & Bianchi, L. (2018) · Drug Design Development and Therapy · doi:10.2147/dddt.s155610 · Cited by 34 · see citing works
He, P., Dong, W., Chu, X., Feng, M., & Ying, S. (2016) · Environmental Microbiology · doi:10.1111/1462-2920.13500 · Cited by 34 · see citing works
Juvvadi, P. R., & Steinbach, W. J. (2015) · Pathogens · doi:10.3390/pathogens4040883 · Cited by 33 · see citing works
Self-citationDistinct Roles of Myosins in Aspergillus fumigatus Hyphal Growth and Pathogenesis
Renshaw, H., Vargas-Muñiz, J. M., Richards, A. D., Asfaw, Y. G., Juvvadi, P. R., & Steinbach, W. J. (2016) · Infection and Immunity · doi:10.1128/iai.01190-15 · Cited by 32 · see citing works
Self-citationChaperone Networks in Fungal Pathogens of Humans
Horianopoulos, L. C., & Kronstad, J. W. (2021) · Journal of Fungi · doi:10.3390/jof7030209 · Cited by 29 · see citing works
Lamoth, F., Juvvadi, P. R., Soderblom, E. J., Moseley, M. A., & Steinbach, W. J. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00946-15 · Cited by 32 · see citing works
Self-citationStructure-guided approaches to targeting stress responses in human fungal pathogens
LeBlanc, E. V., Polvi, E. J., Veri, A. O., Privé, G. G., & Cowen, L. E. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.013731 · Cited by 31 · see citing works
Novel Promising Antifungal Target Proteins for Conquering Invasive Fungal Infections
Zhen, C., Lu, H., & Jiang, Y. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.911322 · Cited by 33 · see citing works
The molecular mechanism of azole resistance in Aspergillus fumigatus: from bedside to bench and back
Wei, X., Zhang, Y., & Lü, L. (2015) · The Journal of Microbiology · doi:10.1007/s12275-015-5014-7 · Cited by 31 · see citing works
Heat Shock Proteins in Dermatophytes: Current Advances and Perspectives
Martinez-Rossi, N. M., Jacob, T. R., Sanches, P. R., Peres, N. T. A., Lang, E. A. S., Martins, M. P., & Rossi, A. (2015) · Current Genomics · doi:10.2174/1389202917666151116212437 · Cited by 31 · see citing works
The eagle-like effect of echinocandins: what’s in a name?
Vanstraelen, K., Lagrou, K., Maertens, J., Wauters, J., Willems, L., & Spriet, I. (2013) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.2013.841543 · Cited by 28 · see citing works
Promising immunotherapeutic targets for treating candidiasis
Feng, Z. C., Lu, H., & Jiang, Y. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1339501 · Cited by 27 · see citing works
Wu, J., Wang, M., Zhou, L., & Yu, D. (2015) · Gene · doi:10.1016/j.gene.2015.09.044 · Cited by 28 · see citing works
To Sense or Die: Mechanisms of Temperature Sensing in Fungal Pathogens
Leach, M. D., & Cowen, L. E. (2014) · Current Fungal Infection Reports · doi:10.1007/s12281-014-0182-1 · Cited by 28 · see citing works
Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections
Neves‐da‐Rocha, J., Santos-Saboya, M. J., Lopes, M. E. R., Rossi, A., & Martinez-Rossi, N. M. (2023) · Microorganisms · doi:10.3390/microorganisms11081878 · Cited by 27 · see citing works
Antifungal Drugs: The Current Armamentarium and Development of New Agents
Robbins, N., Wright, G. D., & Cowen, L. E. (2017) · ASM Press eBooks · doi:10.1128/9781555819583.ch44 · Cited by 26 · see citing works
Schubert, M., Xue, S., Ebel, F., Vaggelas, A., Krylov, V. B., Nifantiev, N. E., Chudobová, I., Schillberg, S., & Nölke, G. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00234 · Cited by 26 · see citing works
Gao, X., Wang, Q., Feng, Q., Zhang, B., He, C., Luo, H., & An, B. (2022) · Journal of Fungi · doi:10.3390/jof8020175 · Cited by 25 · see citing works
Vargas-Muñiz, J. M., Renshaw, H., Richards, A. D., Waitt, G. M., Soderblom, E. J., Moseley, M. A., Asfaw, Y. G., Juvvadi, P. R., & Steinbach, W. J. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00997 · Cited by 24 · see citing works
Self-citationOld and new strategies in therapy and diagnosis against fungal infections
Vanzolini, T., & Magnani, M. (2024) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-023-12884-8 · Cited by 24 · see citing works
Campione, E., Gaziano, R., Doldo, E., Marino, D., Falconi, M., Iacovelli, F., Tagliaferri, D., Pacello, L., Bianchi, L., Lanna, C., et al. (2020) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01874-20 · Cited by 23 · see citing works
Epigenetic and Posttranslational Modifications in Regulating the Biology of Aspergillus Species
Nie, X., Li, B., & Wang, S. (2018) · Advances in applied microbiology · doi:10.1016/bs.aambs.2018.05.004 · Cited by 21 · see citing works
Chu, X., Feng, M., & Ying, S. (2015) · Current Genetics · doi:10.1007/s00294-015-0517-7 · Cited by 20 · see citing works
Araújo, D. S., Lima, P. D. S., Baeza, L. C., Parente, A. F. A., Bailão, A. M., Borges, C. L., & Soares, C. M. D. A. (2017) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2017.08.016 · Cited by 19 · see citing works
Phosphoproteomics of Aspergillus fumigatus Exposed to the Antifungal Drug Caspofungin
Mattos, E. C., Palmisano, G., & Goldman, G. H. (2020) · mSphere · doi:10.1128/msphere.00365-20 · Cited by 19 · see citing works
Effect of Nitrosative Stress on the S-Nitroso-Proteome of Paracoccidioides brasiliensis
Navarro, M. V., Chaves, A. F. A., Castilho, D. G., Casula, I., Calado, J. C. P., Conceição, P. M., Iwai, L. K., de Castro, B. F., & Batista, W. L. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.01184 · Cited by 18 · see citing works
Li, H., Lu, Z., Zhu, Q. C., Gong, J., Geng, Y., Shi, J., Xu, Z., & Ma, Y. (2017) · PROTEOMICS · doi:10.1002/pmic.201700256 · Cited by 17 · see citing works
Proteomic analysis of Aspergillus niger 3.316 under heat stress
Deng, X., Du, B., Zhu, F., Gao, Y., & Li, J. (2020) · MicrobiologyOpen · doi:10.1002/mbo3.1012 · Cited by 17 · see citing works
Moura, Á. N. D., de Oliveira, D. S. L., Paredes, V., Rocha, L. B., de Oliveira, F. S., Lessa, G., Riasco-Palacios, J., Casadevall, A., Albuquerque, P., Felipe, M. S. S., et al. (2020) · Journal of Fungi · doi:10.3390/jof6040193 · Cited by 16 · see citing works
Aruanno, M., Bachmann, D., Sanglard, D., & Lamoth, F. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00208-19 · Cited by 16 · see citing works
Self-citationAlaalm, L., Crunden, J. L., Butcher, M. C., Obst, U., Whealy, R. N., Williamson, C. E., O’Brien, H., Schaffitzel, C., Ramage, G., SPENCER, J. M., et al. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.637836 · Cited by 16 · see citing works
Novel Treatment Approach for Aspergilloses by Targeting Germination
Verburg, K., van Neer, J., Duca, M., & de Cock, H. (2022) · Journal of Fungi · doi:10.3390/jof8080758 · Cited by 16 · see citing works
RNA thermometers and other regulatory elements: Diversity and importance in bacterial pathogenesis
Sharma, A., Alajangi, H. K., Pisignano, G., Sood, V., Singh, G., & Barnwal, R. P. (2022) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1711 · Cited by 15 · see citing works
Synergistic effects of vorinostat (SAHA) and azoles against Aspergillus species and their biofilms
Tu, B., Yin, G., & Li, H. (2020) · BMC Microbiology · doi:10.1186/s12866-020-1718-x · Cited by 15 · see citing works
Fang, T., Xiong, J., Huang, X., Fang, X., Shen, X., Jiang, Y., & Lu, H. (2024) · Microbiological Research · doi:10.1016/j.micres.2024.127964 · Cited by 14 · see citing works
Pennerman, K. K., Yin, G., Bennett, J. W., & Hua, S.-S. T. (2019) · Journal of Fungi · doi:10.3390/jof5020053 · Cited by 14 · see citing works
Trade-Offs Between Growth Rate and Other Fungal Traits
Lovero, K. G., & Treseder, K. K. (2021) · Frontiers in Forests and Global Change · doi:10.3389/ffgc.2021.756650 · Cited by 13 · see citing works
Ancuceanu, R., Hovaneț, M. V., Maria, C.-T., Anghel, A.-I., & Dinu, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012543 · Cited by 13 · see citing works
Interdisciplinary approaches for the discovery of novel antifungals
Yiu, B., Robbins, N., & Cowen, L. E. (2024) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2024.04.018 · Cited by 13 · see citing works
Genomic Approaches to Antifungal Drug Target Identification and Validation
Robbins, N., & Cowen, L. E. (2022) · Annual Review of Microbiology · doi:10.1146/annurev-micro-041020-094524 · Cited by 13 · see citing works
Proteomic analysis of Aspergillus fumigatus – clinical implications
Moloney, N. M., Owens, R. A., & Doyle, S. (2016) · Expert Review of Proteomics · doi:10.1080/14789450.2016.1203783 · Cited by 12 · see citing works
Cissé, O. H., Ma, L., & Kovacs, J. A. (2024) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00202-22 · Cited by 11 · see citing works
Heat Shock Protein 90 (Hsp90) in Fungal Growth and Pathogenesis
Lamoth, F., Juvvadi, P. R., & Steinbach, W. J. (2014) · Current Fungal Infection Reports · doi:10.1007/s12281-014-0195-9 · Cited by 10 · see citing works
Self-citationZhao, W., Hao, Y., WANG, L., Zhou, Z., & Li, Z. (2015) · Parasitology · doi:10.1017/s0031182015000190 · Cited by 10 · see citing works
Caspofungin exposure alters the core septin AspB interactome of Aspergillus fumigatus
Vargas-Muñiz, J. M., Renshaw, H., Waitt, G. M., Soderblom, E. J., Moseley, M. A., Palmer, J. M., Juvvadi, P. R., Keller, N. P., & Steinbach, W. J. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.02.116 · Cited by 10 · see citing works
Self-citationLiu, L., Zhang, X., Kayastha, S., Tan, L., Zhang, H., Tan, J., Li, L., Mao, J., & Sun, Y. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.825745 · Cited by 9 · see citing works
Seo, Y. H., Kim, S.-S., & Shin, K.-S. (2015) · Mycobiology · doi:10.5941/myco.2015.43.2.150 · Cited by 9 · see citing works
- Authors
- Lamoth, F., Juvvadi, P. R., Fortwendel, J. R., & Steinbach, W. J.
- Affiliations
- Duke Medical Center (US)
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2012-11
- Volume
- 11
- Issue
- 11
- Pages
- 1324-1332
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC3486032
- OpenAlex
- W2106567443
- Semantic Scholar
- eb6f3834aabdc76c9098700ed11d9c6f343b2fea
- Cited by
- 136
- References
- 42
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 7 · 2023: 5 · 2022: 11 · 2021: 8 · 2020: 12 · 2019: 10 · 2018: 9 · 2017: 11 · 2016: 19 · 2015: 17 · 2014: 10 · 2013: 5 · 2012: 2
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (134303)
- National Institute of Allergy and Infectious Diseases (R56AI077648, T32AI052080)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- HSP90, Aspergillus fumigatus, conidiation, cell wall integrity, molecular chaperones, brlA, weta, abaA, caspofungin, Congo red, FK506, geldanamycin, 17-AAG, 17-DMAG, hyphal growth, spore viability, septum formation, antifungal drug targets, fungal pathogens
- MeSH terms
- Caspofungin, Aspergillus fumigatus, Cell Wall, Cytosol, Fungal Proteins, Promoter Regions, Genetic, Spores, Fungal, Stress, Physiological, Transcription Factors, Transcription, Genetic, Gene Expression Regulation, Fungal, Benzoquinones, Tacrolimus, Gene Deletion, HSP90 Heat-Shock Proteins, Hyphae, Lactams, Macrocyclic, beta-Glucans, Green Fluorescent Proteins, Microbial Viability, Echinocandins, Lipopeptides
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
