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Mode of Action of a Designed Antimicrobial Peptide: High Potency against Cryptococcus neoformans.

Publication ,  Journal Article
Datta, A; Yadav, V; Ghosh, A; Choi, J; Bhattacharyya, D; Kar, RK; Ilyas, H; Dutta, A; An, E; Mukhopadhyay, J; Lee, D; Sanyal, K; Bhunia, A ...
Published in: Biophysical journal
October 2016

There is a significant need for developing compounds that kill Cryptococcus neoformans, the fungal pathogen that causes meningoencephalitis in immunocompromised individuals. Here, we report the mode of action of a designed antifungal peptide, VG16KRKP (VARGWKRKCPLFGKGG) against C. neoformans. It is shown that VG16KRKP kills fungal cells mainly through membrane compromise leading to efflux of ions and cell metabolites. Intracellular localization, inhibition of in vitro transcription, and DNA binding suggest a secondary mode of action for the peptide, hinting at possible intracellular targets. Atomistic structure of the peptide determined by NMR experiments on live C. neoformans cells reveals an amphipathic arrangement stabilized by hydrophobic interactions among A2, W5, and F12, a conventional folding pattern also known to play a major role in peptide-mediated Gram-negative bacterial killing, revealing the importance of this motif. These structural details in the context of live cell provide valuable insights into the design of potent peptides for effective treatment of human and plant fungal infections.

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Published In

Biophysical journal

DOI

EISSN

1542-0086

ISSN

0006-3495

Publication Date

October 2016

Volume

111

Issue

8

Start / End Page

1724 / 1737

Related Subject Headings

  • Nucleic Acid Conformation
  • Models, Molecular
  • DNA
  • Cryptococcus neoformans
  • Cell Nucleus
  • Cell Membrane
  • Biophysics
  • Base Sequence
  • Antimicrobial Cationic Peptides
  • Amino Acid Sequence
 

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Datta, A., Yadav, V., Ghosh, A., Choi, J., Bhattacharyya, D., Kar, R. K., … Bhunia, A. (2016). Mode of Action of a Designed Antimicrobial Peptide: High Potency against Cryptococcus neoformans. Biophysical Journal, 111(8), 1724–1737. https://doi.org/10.1016/j.bpj.2016.08.032
Datta, Aritreyee, Vikas Yadav, Anirban Ghosh, Jaesun Choi, Dipita Bhattacharyya, Rajiv K. Kar, Humaira Ilyas, et al. “Mode of Action of a Designed Antimicrobial Peptide: High Potency against Cryptococcus neoformans.Biophysical Journal 111, no. 8 (October 2016): 1724–37. https://doi.org/10.1016/j.bpj.2016.08.032.
Datta A, Yadav V, Ghosh A, Choi J, Bhattacharyya D, Kar RK, et al. Mode of Action of a Designed Antimicrobial Peptide: High Potency against Cryptococcus neoformans. Biophysical journal. 2016 Oct;111(8):1724–37.
Datta, Aritreyee, et al. “Mode of Action of a Designed Antimicrobial Peptide: High Potency against Cryptococcus neoformans.Biophysical Journal, vol. 111, no. 8, Oct. 2016, pp. 1724–37. Epmc, doi:10.1016/j.bpj.2016.08.032.
Datta A, Yadav V, Ghosh A, Choi J, Bhattacharyya D, Kar RK, Ilyas H, Dutta A, An E, Mukhopadhyay J, Lee D, Sanyal K, Ramamoorthy A, Bhunia A. Mode of Action of a Designed Antimicrobial Peptide: High Potency against Cryptococcus neoformans. Biophysical journal. 2016 Oct;111(8):1724–1737.
Journal cover image

Published In

Biophysical journal

DOI

EISSN

1542-0086

ISSN

0006-3495

Publication Date

October 2016

Volume

111

Issue

8

Start / End Page

1724 / 1737

Related Subject Headings

  • Nucleic Acid Conformation
  • Models, Molecular
  • DNA
  • Cryptococcus neoformans
  • Cell Nucleus
  • Cell Membrane
  • Biophysics
  • Base Sequence
  • Antimicrobial Cationic Peptides
  • Amino Acid Sequence