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The novel antifungal agent AB-22 displays in vitro activity against hyphal growth and biofilm formation in Candida albicans and potency for treating systemic candidiasis

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
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Abstract

Systemic candidiasis, which is mainly caused by Candida albicans, is a serious acute fungal infection in the clinical setting. In a previous study, we reported that compound 22h (designated as AB-22 in this study), a vinyl sulfate compound, is a fast-acting fungicidal agent against a broad spectrum of fungal pathogens. In this study, we aimed to further analyze the in vitro and in vivo efficacy of AB-22 against filamentation, biofilm formation, and virulence of C. albicans. Under in vitro hyphal growth-inducing condition, AB-22 effectively inhibited germ tube formation and hyphal growth, which are required for the initiation of biofilm formation. Indeed, AB-22 significantly suppressed C. albicans biofilm formation in a dose-dependent manner. Moreover, AB-22 treatment inhibited the normal induction of ALS3, HWP1, and ECE1, which are all required for hyphal transition in C. albicans. Furthermore, AB-22 treatment increased the survival of mice systemically infected with C. albicans. In conclusion, in addition to its fungicidal activity, AB-22 inhibits filamentation and biofilm formation in C. albicans, which could collectively contribute to its potent in vivo efficacy against systemic candidiasis.

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References

  • Andes, D.R., Safdar, N., Baddley, J.W., Playford, G., Reboli, A.C., Rex, J.H., Sobel, J.D., Pappas, P.G., Kullberg, B.J., and Mycoses Study Group. 2012. Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials. Clin. Infect. Dis. 54, 1110–1122.

    Article  CAS  Google Scholar 

  • Birse, C.E., Irwin, M.Y., Fonzi, W.A., and Sypherd, P.S. 1993. Cloning and characterization of ECE1, a gene expressed in association with cell elongation of the dimorphic pathogen Candida albicans. Infect. Immun. 61, 3648–3655.

    Article  CAS  Google Scholar 

  • Carlisle, P.L. and Kadosh, D. 2010. Candida albicans Ume6, a filament-specific transcriptional regulator, directs hyphal growth via a pathway involving Hgc1 cyclin-related protein. Eukaryot. Cell 9, 1320–1328.

    Article  CAS  Google Scholar 

  • Choi, J.W., Lee, K.T., Kim, S., Lee, Y.R., Kim, H.J., Seo, K.J., Lee, M.H., Yeon, S.K., Jang, B.K., Park, S.J., et al. 2021. Optimization and evaluation of novel antifungal agents for the treatment of fungal infection. J. Med. Chem. 64, 15912–15935.

    Article  CAS  Google Scholar 

  • Clancy, C.J. and Nguyen, M.H. 2013. Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin. Infect. Dis. 56, 1284–1292.

    Article  Google Scholar 

  • Cowen, L.E., Sanglard, D., Howard, S.J., Rogers, P.D., and Perlin, D.S. 2014. Mechanisms of antifungal drug resistance. Cold Spring Harb. Perspect. Med. 5, a019752.

    Article  Google Scholar 

  • Finkel, J.S. and Mitchell, A.P. 2011. Genetic control of Candida albicans biofilm development. Nat. Rev. Microbiol. 9, 109–118.

    Article  CAS  Google Scholar 

  • Fraser, V.J., Jones, M., Dunkel, J., Storfer, S., Medoff, G., and Dunagan, W.C. 1992. Candidemia in a tertiary care hospital: epidemiology, risk factors, and predictors of mortality. Clin. Infect. Dis. 15, 414–421.

    Article  CAS  Google Scholar 

  • Gow, N.A., van de Veerdonk, F.L., Brown, A.J., and Netea, M.G. 2011. Candida albicans morphogenesis and host defence: discriminating invasion from colonization. Nat. Rev. Microbiol. 10, 112–122.

    Article  Google Scholar 

  • Masiá Canuto, M. and Gutiérrez Rodero, F. 2002. Antifungal drug resistance to azoles and polyenes. Lancet Infect. Dis. 2, 550–563.

    Article  Google Scholar 

  • Nobile, C.J., Andes, D.R., Nett, J.E., Smith, F.J. Jr, Yue, F., Phan, Q.T., Edwards, J.E. Jr, Filler, S.G., and Mitchell, A.P. 2006. Critical role of Bcr1-dependent adhesins in C. albicans biofilm formation in vitro and in vivo. PLoS Pathog. 2, e63.

    Article  Google Scholar 

  • Nobile, C.J. and Johnson, A.D. 2015. Candida albicans biofilms and human disease. Annu. Rev. Microbiol. 69, 71–92.

    Article  CAS  Google Scholar 

  • Nobile, C.J. and Mitchell, A.P. 2005. Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcr1p. Curr. Biol. 15, 1150–1155.

    Article  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Park, S., Kelly, R., Kahn, J.N., Robles, J., Hsu, M.J., Register, E., Li, W., Vyas, V., Fan, H., Abruzzo, G., et al. 2005. Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates. Antimicrob. Agents Chemother. 49, 3264–3273.

    Article  CAS  Google Scholar 

  • Perlin, D.S. 2011. Current perspectives on echinocandin class drugs. Future Microbiol. 6, 441–457.

    Article  CAS  Google Scholar 

  • Perlin, D.S. 2015. Echinocandin resistance in Candida. Clin. Infect. Dis. 61, S612–S617.

    Article  CAS  Google Scholar 

  • Pristov, K.E. and Ghannoum, M.A. 2019. Resistance of Candida to azoles and echinocandins worldwide. Clin. Microbiol. Infect. 25, 792–798.

    Article  CAS  Google Scholar 

  • Saville, S.P., Thomas, D.P., and Lopez Ribot, J.L. 2006. A role for Efg1p in Candida albicans interactions with extracellular matrices. FEMS Microbiol. Lett. 256, 151–158.

    Article  CAS  Google Scholar 

  • Staab, J.F., Bradway, S.D., Fidel, P.L., and Sundstrom, P. 1999. Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1. Science 283, 1535–1538.

    Article  CAS  Google Scholar 

  • Warrilow, A.G., Parker, J.E., Kelly, D.E., and Kelly, S.L. 2013. Azole affinity of sterol 14α-demethylase (CYP51) enzymes from Candida albicans and Homo sapiens. Antimicrob. Agents Chemother. 57, 1352–1360.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by the Korea Health Technology R&D Project (HI20C0326 to J.-S.L. and K.-T.L.) by the Ministry of Health and Welfare, Republic of Korea.

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Correspondence to Jong-Seung Lee or Yong-Sun Bahn.

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All animal experiments were performed in accordance with the guidelines of the Animal Care and Use Committee of the Institutional Animal Care and Use in the NDIC (approved No. P201099 and P201103).

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Conflict of Interest

The authors declare the following competing financial interests: AmtixBio, Co., Ltd., Yonsei University, and Korea University of Science and Technology have jointly filed patent applications (Korea Patent No. 10-2021-0194152 and PCT/KR2021/020377) related to in vivo efficacy of AB-22. Y.-S.B. is scientific co-founder and J.-S.L. is chief executive officer of AmtixBio, Co., Ltd. Y.-S.B. and J.-S.L. are stockholders of AmtixBio, Co., Ltd. All other authors declare no conflict of interest.

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Lee, KT., Lee, DG., Choi, J.W. et al. The novel antifungal agent AB-22 displays in vitro activity against hyphal growth and biofilm formation in Candida albicans and potency for treating systemic candidiasis. J Microbiol. 60, 438–443 (2022). https://doi.org/10.1007/s12275-022-2016-0

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  • DOI: https://doi.org/10.1007/s12275-022-2016-0

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