CoChat
Sign Up
Cited by 31Fungal and yeast genetics researchAntifungal resistance and susceptibilityFungal Infections and Studies

Crosstalk between the calcineurin and cell wall integrity pathways prevents chitin overexpression in Candida albicans

Open access
da Silva Dantas, Alessandra, Nogueira, Filomena, Lee, Keunsook K., Walker, Louise A., Edmondson, Matt, Brand, Alexandra C., Lenardon, Megan D., Gow, Neil A. R.·2021·Journal of Cell Science
DOI 10.1242/jcs.258889PMC PMC8729787
Open this paper in CoChat — free accountOpen PDF

Abstract

Echinocandins such as caspofungin are frontline antifungal drugs that compromise β-1,3 glucan synthesis in the cell wall. Recent reports have shown that fungal cells can resist killing by caspofungin by upregulation of chitin synthesis, thereby sustaining cell wall integrity (CWI). When echinocandins are removed, the chitin content of cells quickly returns to basal levels, suggesting that there is a fitness cost associated with having elevated levels of chitin in the cell wall. We show here that simultaneous activation of the calcineurin and CWI pathways generates a subpopulation of Candida albicans yeast cells that have supra-normal chitin levels interspersed throughout the inner and outer cell wall, and that these cells are non-viable, perhaps due to loss of wall elasticity required for cell expansion and growth. Mutations in the Ca2+-calcineurin pathway prevented the formation of these non-viable supra-high chitin cells by negatively regulating chitin synthesis driven by the CWI pathway. The Ca2+-calcineurin pathway may therefore act as an attenuator that prevents the overproduction of chitin by coordinating both chitin upregulation and negative regulation of the CWI signaling pathway. This article has an associated First Person interview with the first author of the paper.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1242/jcs.258889

Cites

16 of 16 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Cell wall adaptation to echinocandins is characterized by increased levels and exposure of chitin following depletion of a substantial portion of β-glucan.

    “These effects have been associated with cell wall adaptation to echinocandins, characterized by increased levels and exposure of chitin following the depletion of a substantial portion of β-glucan; however, our understanding of echinocandin-induced remodeling mechanism of Candida cell wall architecture remains limited24,27–29.”

    From Distinct echinocandin responses of Candida albicans and Candida auris cell walls revealed by solid-state NMR (2025) · cites this paper as [29]

    The Discussion (page unavailable) reports that caspofungin-treated cells have increased wall chitin alongside decreased β-1,3-glucan, and that some chitin becomes more accessible at the wall surface. It does not establish that a substantial portion of β-glucan was depleted, so that magnitude is unsupported. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • This rigidification may be a result of chitin relocation from the inner to the outer layer, which also enhanced chitin-protein association.

    “This may be a result of chitin relocation from the inner to the outer layer, which also enhanced chitin-protein association, as recently reported (Fig. 8)29.”

    From Distinct echinocandin responses of Candida albicans and Candida auris cell walls revealed by solid-state NMR (2025) · cites this paper as [29]

    The Results and Discussion (Figs 2 and 8; page unavailable) report increased chitin exposure in the outer wall after caspofungin treatment and suggest that chitin distributed through the wall may increase rigidity. They do not report that this relocation enhanced chitin–protein association; the Discussion instead mentions chitin–glucan cross-linking as a possible influence on rigidity. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • A recent study using high molecular weight lectin to stain C. albicans cell walls revealed an increased level of surface-exposed chitin following caspofungin treatment.

    “A recent study using high molecular weight lectin to stain C. albicans cell walls—which can access only the outer layer and not penetrate the inner layer—revealed an increased level of surface-exposed chitin following caspofungin treatment29.”

    From Distinct echinocandin responses of Candida albicans and Candida auris cell walls revealed by solid-state NMR (2025) · cites this paper as [29]

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

Flagged first, then by citations

Research works printed but not linked: 67

  1. Altwasser, R., Baldin, C., Weber, J., Guthke, R., Kniemeyer, O., Brakhage, A. A., Linde, J. and Valiante, V. (2015). Network modeling reveals cross talk of MAP kinases during adaptation to caspofungin stress in Aspergillus fumigatus. PLoS ONE 10, e0136932. 10.1371/journal.pone.0136932 26356475 PMC4565559 · DOI
  2. Astvad, K. M., Perlin, D. S., Johansen, H. K., Jensen, R. H. and Arendrup, M. C. (2013). Evaluation of caspofungin susceptibility testing by the new Vitek 2 AST-YS06 yeast card using a unique collection of FKS wild-type and hot spot mutant isolates, including the five most common Candida species. Antimicrob. Agents Chemother. 57, 177- 182. 10.1128/AAC.01382-12 23089746 PMC3535959 · DOI · Paper page
  3. Bates, S., MacCallum, D. M., Bertram, G., Munro, C. A., Hughes, H. B., Buurman, E. T., Brown, A. J., Odds, F. C. and Gow, N. A. (2005). Candida albicans Pmr1p, a secretory pathway P-type Ca2+/Mn2+-ATPase, is required for glycosylation and virulence. J. Biol. Chem. 280, 23408- 23415. 10.1074/jbc.M502162200 15843378 · DOI
  4. Ben-Ami, R., Garcia-Effron, G., Lewis, R. E., Gamarra, S., Leventakos, K., Perlin, D. S. and Kontoyiannis, D. P. (2011). Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance. J. Infect. Dis. 204, 626- 635. 10.1093/infdis/jir351 21791665 PMC3144175 · DOI · Paper page
  5. Bizerra, F. C., Melo, A. S. A., Katchburian, E., Freymüller, E., Straus, A. H., Takahashi, H. K. and Colombo, A. L. (2011). Changes in cell wall synthesis and ultrastructure during paradoxical growth effect of caspofungin on four different Candida species. Antimicrob. Agents Chemother. 55, 302- 310. 10.1128/AAC.00633-10 21060107 PMC3019691 · DOI
  6. Brand, A., MacCallum, D. M., Brown, A. J. P., Gow, N. A. R. and Odds, F. C. (2004). Ectopic expression of URA3 can influence the virulence phenotypes and proteome of Candida albicans but can be overcome by targeted reintegration of URA3 at the RPS10 locus. Eukaryot. Cell 3, 900- 909. 10.1128/EC.3.4.900-909.2004 15302823 PMC500875 · DOI
  7. Brand, A., Shanks, S., Duncan, V. M. S., Yang, M., Mackenzie, K. and Gow, N. A. R. (2007). Hyphal orientation of Candida albicans is regulated by a calcium-dependent mechanism. Curr. Biol. 17, 347- 352. 10.1016/j.cub.2006.12.043 17275302 PMC1885950 · DOI
  8. Bruno, V. M., Kalachikov, S., Subaran, R., Nobile, C. J., Kyratsous, C. and Mitchell, A. P. (2006). Control of the C. albicans cell wall damage response by transcriptional regulator Cas5. PLoS Pathog. 2, e21. 10.1371/journal.ppat.0020021 16552442 PMC1401495 · DOI · Paper page
  9. Chaudhari, R. D., Stenson, J. D., Obverton, T. W. and Thomas, C. R. (2012). Effect of bud scars on the mechanical properties of Saccharomyces cerevisiae cell walls. Chem. Eng. Sci. 84, 188- 196. 10.1016/j.ces.2012.08.027 · DOI
  10. Colabardini, A. C., Ries, L. N. A., Brown, N. A., Savoldi, M., Dinamarco, T. M., von Zeska, M. R., Goldman, M. H. S. and Goldman, G. H. (2014). Protein kinase C overexpression suppresses calcineurin-associated defects in Aspergillus nidulans and is involved in mitochondrial function. PLoS ONE 9, e104792. 10.1371/journal.pone.0104792 25153325 PMC4143261 · DOI
  11. Coste, A. T., Karababa, M., Ischer, F., Bille, J. and Sanglard, D. (2004). TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2. Eukaryot. Cell 3, 1639- 1652. 10.1128/ec.3.6.1639-1652.2004 15590837 PMC539021 · DOI · Paper page
  12. Dantas, A., Lee, K. K., Raziunaite, I., Schaefer, K., Wagener, J., Yadav, B. and Gow, N. A. R. (2017). Cell biology of Candida albicans – host interactions. Curr. Opin. Microbiol. 34, 111- 118. 10.1016/j.mib.2016.08.006 PMC5660506 27689902 · DOI
  13. Denning, D. W. (2003). Echinocandin antifungal drugs. Lancet 362, 1142- 1151. 10.1016/S0140-6736(03)14472-8 14550704 · DOI · Paper page
  14. Denning, D. W., Kneale, M., Sobel, J. D. and Rautemaa-Richardson, R. (2018). Global burden of recurrent vulvovaginal candidiasis: a systematic review. Lancet Infect. Dis. 18, e339- e347. 10.1016/S1473-3099(18)30103-8 30078662 · DOI · Paper page
  15. Donlin, M. J., Upadhya, R., Gerik, K. J., Lam, W., VanArendonk, L. G., Specht, C. A., Sharma, N. K. and Lodge, J. K. (2014). Cross talk between the cell wall integrity and cyclic AMP/protein kinase A pathways in Cryptococcus neoformans. mBio 5, e01514- e01573. 10.1128/mBio.01573-14 PMC4145688 25118241 · DOI
  16. Drakulovski, P., Dunyach, C., Bertout, S., Reynes, J. and Mallié, M. (2011). A Candida albicans strain with high MIC for caspofungin and no FKS1 mutations exhibits a high chitin content and mutations in two chitinase genes. Med. Mycol. 49, 467- 474. 10.3109/13693786.2010.538732 21108572 · DOI
  17. Ene, I. J., Walker, L. A., Schiavone, M., Lee, K. K., Martin-Yken, H., Dague, E., Gow, N. A. R., Munro, C. A. and Brown, A. P. J. (2015). Cell wall remodelling enzymes modulate fungal cell wall elasticity and osmotic stress resistance. mBio 6, e00915- e00986. 10.1128/mBio.00986-15 PMC4551979 26220968 · DOI
  18. Fernandes, C., Anjos, J., Walker, L. A., Silva, B. M. A., Cortes, L., Mota, M., Munro, C. A., Gow, N. A. R. and Goncalves, T. (2014). Modulation of Alternaria infectoria cell wall chitin and glucan synthesis by cell wall synthase inhibitors. Antimicrob. Agents. Chemother. 58, 2894- 2904. 10.1128/AAC.02647-13 24614372 PMC3993226 · DOI
  19. Földi, R., Kovács, R., Gesztelyi, R., Kardos, G., Berényi, R., Juhász, B., Szilágyi, J., Mózes, J. and Majoros, L. (2012). Comparison of in vitro and vivo efficacy of caspofungin against Candida parapsilosis, C. orthopsilosis, C. metapsilosis and C. albicans. Mycopathologia 174, 311- 318. 10.1007/s11046-012-9554-7 22565489 · DOI
  20. Fraser, M., Borman, A. M., Thorn, R. and Lawrance, L. M. (2020). Resistance to echinocandin antifungal agents in the United Kingdom in clinical isolates of Candida glabrata: Fifteen years of interpretation and assessment. Med. Mycol. 58, 219- 226. 10.1093/mmy/myz053 31111912 · DOI
  21. Gow, N. A. R. and Gooday, G. W. (1983). Ultrastructure of chitin in hyphae of Candida albicans and other dimorphic and mycelial fungi. Protoplasma. 115, 52- 58. 10.1007/BF01293580 · DOI
  22. Gow, N. A. R., Gooday, G. W., Russell, J. D. and Wilson, M. J. (1987). Infrared and X-ray diffraction data on chitins of variable structure. Carbohydr. Res. 165, 105- 110. 10.1016/0008-6215(87)80082-4 · DOI
  23. Gow, N. A. R., Latgé, J.-P. and Munro, C. A. (2017). The fungal cell wall: structure, biosynthesis and function. In The Fungal Kingdom (ed. J. Heitman, N.A.R. Gow, B. Howlett, P. Crous, E. Stukenbrock and T. James), pp. 227- 292. Microbiology Spectrum ASM Press. PMC11687499 28513415
  24. Healey, K. R., Nagasaki, Y., Zimmerman, M., Kordalewska, M., Park, S., Zhao, Y. and Perlin, D. S. (2017). The gastrointestinal tract is a major source of echinocandin drug resistance in a murine model of Candida glabrata colonization and systemic dissemination. Antimicrob. Agents Chemother. 61, e01412-17. 10.1128/AAC.01412-17 28971865 PMC5700336 · DOI
  25. Hoang, A. T. (2001). Caspofungin acetate: an antifungal agent. Am. J. Health. Syst. Pharm. 58, 1206- 1214. 10.1093/ajhp/58.13.1206 11449878 · DOI
  26. Jiang, L., Wang, J., Asghar, F., Snyder, N. and Cunningham, K. W. (2018). CaGdt1 plays a compensatory role for the calcium pump CaPmr1 in the regulation of calcium signaling and cell wall integrity signaling in Candida albicans. Cell Commun. Signal. 16, 33. 10.1186/s12964-018-0246-x 29954393 PMC6025805 · DOI
  27. Kaloriti, D., Tillmann, A., Cook, E., Jacobsen, M., You, T., Lenardon, M., Ames, L., Barahona, M., Chandrasekaran, K., Coghill, D. et al. (2012). Combinatorial stresses kill pathogenic Candida species. Med. Mycol. 50, 699- 709. 10.3109/13693786.2012.672770 22463109 PMC3483063 · DOI · Paper page
  28. Katiyar, S., Pfaller, M. and Edlind, T. (2006). Candida albicans and Candida glabrata clinical isolates exhibiting reduced echinocandin susceptibility. Antimicrob. Agents Chemother. 50, 2892- 2894. 10.1128/AAC.00349-06 16870797 PMC1538661 · DOI
  29. Kordalewska, M., Lee, A., Park, S., Berrio, I., Chowdhary, A., Zhao, Y. and Perlin, D. S. (2018). Understanding echinocandin resistance in the emerging pathogen Candida auris. Antimicrob. Agents Chemother. 62, e00238-18. 10.1128/AAC.00238-18 29632013 PMC5971591 · DOI · Paper page
  30. Kullberg, B. J. and Arendrup, M. C. (2015). Invasive candidiasis. N. Engl. J. Med. 373, 1445- 1456. 10.1056/NEJMra1315399 26444731 · DOI · Paper page
  31. Kumar, A., Dhamgaye, S., Maurya, I. K., Singh, A., Sharma, M. and Prasad, R. (2014). Curcumin targets cell wall integrity via calcineurin-mediated signaling in Candida albicans. Antimicrob. Agents. Chemother. 58, 167- 175. 10.1128/AAC.01385-13 24145527 PMC3910804 · DOI
  32. Lee, K. K., Kubo, K., Abdelmoneim Abdelaziz, J., Cunningham, I., de Silva Dantas, A., Chen, X., Okada, H., Ohya, Y. and Gow, N. A. R. (2018). Yeast species-specific, differential inhibition of β-1,3-glucan synthesis by poacic acid and caspofungin. The Cell Surface 3, 12- 25. 10.1016/j.tcsw.2018.09.001 30370375 PMC6195761 · DOI
  33. Lenardon, M. D., Munro, C. A. and Gow, N. A. R. (2010). Chitin synthesis and fungal pathogenesis. Curr. Opin. Microbiol. 13, 416- 423. 10.1016/j.mib.2010.05.002 20561815 PMC2923753 · DOI · Paper page
  34. Lenardon, M. D., Sood, P., Dorfmueller, H. C., Brown, A. J. P. and Gow, N. A. R. (2020). Scalar nanostructure of the Candida albicans cell wall; a molecular, cellular and ultrastructural analysis and interpretation. The Cell Surface. 6, 10047. 10.1016/j.tcsw.2020.100047 PMC7691183 33294751 · DOI · Paper page
  35. Liu, T. T., Lee, R. E. B., Barker, K. S., Lee, R. E., Wei, L., Homayouni, R. and Rogers, D. P. (2005). Genome-wide expression profiling of the response to azole, polyene, echinocandin, and pyrimidine antifungal agents in Candida albicans. Antimicrob. Agents Chemother. 49, 2226- 2236. 10.1128/AAC.49.6.2226-2236.2005 15917516 PMC1140538 · DOI · Paper page
  36. Melo, A. S., Colombo, A. L. and Arthington-Skaggs, B. A. (2007). Paradoxical growth effect of caspofungin observed on biofilms and planktonic cells of five different Candida species. Antimicrob. Agents Chemother. 51, 3081- 3088. 10.1128/AAC.00676-07 17591847 PMC2043224 · DOI
  37. Mishra, R., van Drogen, F., Dechant, R., Oh, S., Jeon, N. L., Lee, S. S. and Peter, M. (2017). Protein kinase C and calcineurin cooperatively mediate cell survival under compressive mechanical stress. Proc. Natl. Acad. Sci. USA 114, 13471- 13476. 10.1073/pnas.1709079114 29196524 PMC5754771 · DOI
  38. Mora-Montes, H. M., Netea, M. G., Ferwerda, G., Lenardon, M. D., Brown, G. D., Mistry, A. R., Kullberg, J., O'Callaghan, C. A., Sheth, C. C., Odds, F. C. et al. (2011). Recognition and blocking of innate immunity cells by Candida albicans chitin. Infect. Immun. 79, 1961- 1970. 10.1128/IAI.01282-10 21357722 PMC3088140 · DOI
  39. Mroczyńska, M. and Brillowska-Dąbrowska, A. (2020). Review on current status of echinocandins use. Antibiotics 9, 227. 10.3390/antibiotics9050227 PMC7277767 32370108 · DOI
  40. Munro, C. A., Selvaggini, S., de Bruijn, I., Walker, L., Lenardon, M. D., Gerssen, B., Milne, S., Brown, A. J. and Gow, N. A. R. (2007). The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans. Mol. Microbiol. 63, 1399- 1413. 10.1111/j.1365-2958.2007.05588.x 17302816 PMC2649417 · DOI · Paper page
  41. Noble, S. M. and Johnson, A. D. (2005). Strains and strategies for large-scale gene deletion studies of the diploid human fungal pathogen Candida albicans. Eukaryot. Cell. 4, 298- 309. 10.1128/EC.4.2.298-309.2005 15701792 PMC549318 · DOI · Paper page
  42. Odds, F. C., Brown, A. P. J. and Gow, N. A. R. (2003). Antifungal agents: mechanisms of action. Trends Microbiol. 11, 272- 279. 10.1016/S0966-842X(03)00117-3 12823944 · DOI · Paper page
  43. Pappas, P. G., Lionakis, M. S., Arendrup, M. C., Ostrosky-Zeichner, L. and Kullberg, B. J. (2018). Invasive candidiasis. Nat. Rev. Dis. Primers 4, 18026. 10.1038/nrdp.2018.26 29749387 · DOI · Paper page
  44. Patil, A. and Majumdar, S. (2017). Echinocandins in antifungal pharmacotherapy. J. Pharm. Pharmacol. 69, 1635- 1660. 10.1111/jphp.12780 28744860 · DOI · Paper page
  45. Perlin, D. S. (2015). Mechanisms of echinocandin antifungal drug resistance. Ann. N. Y. Acad. Sci. 1354, 1- 11. 10.1111/nyas.12831 26190298 PMC4626328 · DOI · Paper page
  46. Perlin, D. S. (2020). Cell wall-modifying antifungal drugs. Curr. Top. Microbiol. Immunol. 425, 255- 275. 10.1007/82_2019_188 31875267 · DOI
  47. Perlin, D. S., Rautemaa-Richardson, R. and Alastruey-Izquierdo, A. (2017). The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet. Infect. Dis. 17, e383- e392. 10.1016/S1473-3099(17)30316-X 28774698 · DOI · Paper page
  48. Pfaller, M. A., Diekema, D. J., Turnidge, J. D., Castanheira, M. and Jones, R. N. (2019). Twenty years of the SENTRY antifungal surveillance program: results for Candida species from 1997-2016. Open Forum Infect. Dis. 6 Suppl. 1, S79- S94. 10.1093/ofid/ofy358 30895218 PMC6419901 · DOI · Paper page
  49. Pianalto, K. M., Billmyre, R. B., Telzrow, C. L. and Alspaugh, J. A. (2019). Roles for stress response and cell wall biosynthesis pathways in caspofungin tolerance in Cryptococcus neoformans. Genetics. 213, 213- 227. 10.1534/genetics.119.302290 31266771 PMC6727808 · DOI · Paper page
  50. Reedy, J. L., Filler, S. G. and Heitman, J. (2010). Elucidating the Candida albicans calcineurin signaling cascade controlling stress response and virulence. Fungal Genet. Biol. 47, 107- 116. 10.1016/j.fgb.2009.09.002 19755168 PMC2815136 · DOI · Paper page
  51. Roemer, T., Jiang, B., Davison, J., Ketela, T., Veillette, K., Breton, A., Tandia, F., Linteau, A., Sillaots, S., Marta, C. et al. (2003). Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery. Mol. Microbiol. 50, 167- 181. 10.1046/j.1365-2958.2003.03697.x 14507372 · DOI
  52. Rueda, C., Cuenca-Estrella, M. and Zaragoza, O. (2014). Paradoxical growth of Candida albicans in the presence of caspofungin is associated with multiple cell wall rearrangements and decreased virulence. Antimicrob. Agents Chemother. 58, 1071- 1083. 10.1128/AAC.00946-13 24295973 PMC3910852 · DOI
  53. Sanguinetti, M., Posteraro, B. and Lass-Flörl, C. (2015). Antifungal drug resistance among Candida species: mechanisms and clinical impact. Mycoses. 58 Suppl. 2, 2- 13. 10.1111/myc.12330 26033251 · DOI · Paper page
  54. Shields, R. K., Nguyen, M. H., Du, C., Press, E., Cheng, S. and Clancy, C. J. (2011). Paradoxical effect of caspofungin against Candida bloodstream isolates is mediated by multiple pathways but eliminated in human serum. Antimicrob. Agents Chemother. 55, 2641- 2647. 10.1128/AAC.00999-10 21422223 PMC3101391 · DOI · Paper page
  55. Shields, R. K., Nguyen, M. H. and Clancy, C. J. (2015a). Clinical perspectives on echinocandin resistance among Candida species. Curr. Opin. Infect. Dis. 28, 514- 522. 10.1097/QCO.0000000000000215 26524326 PMC4632243 · DOI
  56. Steinbach, W. J. and Perfect, J. R. (2003). Newer antifungal therapy for emerging fungal pathogens. Int. J. Infect. Dis. 7, 5- 20. 10.1016/S1201-9712(03)90037-3 12718805 · DOI
  57. Stevens, D. A., Ichinomiya, M., Koshi, Y. and Horiuchi, H. (2006). Escape of Candida from Caspofungin inhibition at concentrations above the MIC (paradoxical effect) accomplished by increased cell wall chitin; evidence for β-1,6-glucan synthesis inhibition by caspofungin. Antimicrob. Agents. Chemother. 50, 3160- 3161. 10.1128/AAC.00563-06 16940118 PMC1563524 · DOI · Paper page
  58. Touhami, A., Nysten, B. and Dufrêne, Y. F. (2003). Nanoscale mapping of the elasticity of microbial cells by atomic force microscopy. Langmuir 19, 4539- 4543. 10.1021/la034136x · DOI
  59. Walker, L., Gow, N. A. R. and Munro, C. A. (2010). Fungal echinocandin resistance. Fungal Genet. Biol. 47, 117- 126. 10.1016/j.fgb.2009.09.003 19770064 PMC2812698 · DOI · Paper page
  60. Walker, L. A., Lee, K. K., Munro, C. A. and Gow, N. A. R. (2015). Caspofungin treatment of Aspergillus fumigatus results in ChsG-dependent upregulation of chitin synthesis and the formation of chitin-rich microcolonies. Antimicrob. Agents Chemother. 59, 5932- 5941. 10.1128/AAC.00862-15 26169407 PMC4576100 · DOI
  61. Wiederhold, N. P. (2009). Paradoxical echinocandin activity: a limited in vitro phenomenon? Med. Mycol. 47 Suppl. 1 S369- S375. 10.1080/13693780802428542 19255904 · DOI
  62. Wilson, R. B., Davis, D. and Mitchell, A. P. (1999). Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J. Bacteriol. 181, 1868- 1874. 10.1128/JB.181.6.1868-1874.1999 10074081 PMC93587 · DOI
  63. Wilson, R. B., Davis, D., Enloe, B. M. and Mitchell, A. P. (2000). A recyclable Candida albicans URA3 cassette for PCR product-directed gene disruptions. Yeast 16, 65- 70. 10.1002/(SICI)1097-0061(20000115)16:1<65::AID-YEA508>3.0.CO;2-M 10620776 · DOI
  64. Yang, M., Brand, A., Srikantha, T., Daniels, K., Soll, D. R. and Gow, N. A. R. (2011). Fig1 facilitates calcium influx and localises to membranes destined to undergo fusion during mating in Candida albicans. Eukaryot. Cell 10, 435- 444. 10.1128/EC.00145-10 21216943 PMC3067472 · DOI
  65. Yang, F., Kravets, A., Bethlendy, G., Welle, S. and Rustchenko, E. (2013). Chromosome 5 monosomy of Candida albicans controls susceptibility to various toxic agents, including major antifungals. Antimicrob. Agents Chemother. 57, 5026- 5036. 10.1128/AAC.00516-13 23896475 PMC3811469 · DOI · Paper page
  66. Yang, F., Zhang, L., Wakabayashi, H., Myers, J., Jiang, Y., Cao, Y., Jimenez-Ortigosa, C., Perlin, D. S. and Rustchenko, E. (2017). Tolerance to caspofungin in Candida albicans is associated with at least three distinctive mechanisms that govern expression of FKS genes and cell wall remodeling. Antimicrob. Agents. Chemother. 61, e00071-17. 10.1128/AAC.00071-17 28223384 PMC5404545 · DOI · Paper page
  67. Yu, Q., Wang, F., Zhao, Q., Chen, J., Zhang, B., Ding, X., Wang, H., Yang, B., Lu, G., Zhang, B. et al. (2014). A novel role of the vacuolar calcium channel Yvc1 in stress response, morphogenesis and pathogenicity of Candida albicans. Int. J. Med. Microbiol. 304, 339- 350. 10.1016/j.ijmm.2013.11.022 24368068 · DOI

Cited by

Sorted by citations

Authors
da Silva Dantas, A., Nogueira, F., Lee, K. K., Walker, L. A., Edmondson, M., Brand, A. C., Lenardon, M. D., & Gow, N. A. R.
Affiliations
  • School of Biosciences, University of Exeter, Geoffrey Pope Building, Exeter EX4 4QD, UK
  • University of Aberdeen (GB)
  • University of Exeter (GB)
Corresponding author
Gow, Neil A. R.
ORCID
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2021-12-15
Volume
134
Issue
24
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.258889
PMC
PMC8729787
OpenAlex
W3212638803
Cited by
31
References
16
Citations by year
2026: 9 · 2025: 10 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 1
FWCI
0.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cell Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
Funders
  • Wellcome Trust (101873/Z/13/Z, 086827, 097377/Z11/Z, 215599/Z/19/Z, 200208/A/15/Z)
  • Medical Research Council (MR/N006364/2)
  • Marie Curie (MB004 RGE0655 ARIADNE)
  • University of Exeter
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
Candida albicans, calcineurin signaling, cell wall integrity pathway, chitin synthesis, echinocandin resistance, caspofungin, β-1,3-glucan, cell wall elasticity, pathway crosstalk, fitness cost
MeSH terms
Candida albicans, Cell Wall, Chitin, Fungal Proteins, Humans, Calcineurin, 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