Antibacterial, antifungal, anticancer activities and structural bioinformatics analysis of six naturally occurring temporins

Biswajit Mishra, Xiuqing Wang, Tamara Lushnikova, Yingxia Zhang, Radha M. Golla, Jayaram Lakshmaiah Narayana, Chunfeng Wang, Timothy R McGuire, Guangshun Wang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Antimicrobial peptides are a special class of natural products with potential applications as novel therapeutics. This study focuses on six temporins (four with no activity data and two as positive controls). Using synthetic peptides, we report antibacterial, antifungal, and anticancer activities of temporins-CPa, CPb, 1Ga, 1Oc, 1Ola, and 1SPa. While temporin-1Ga and temporin-1OLa showed higher antifungal and anticancer activity, most of these peptides were active primarily against Gram-positive bacteria. Temporin-1OLa, with the highest cell selectivity index, could preferentially kill methicillin-resistant Staphylococcus aureus (MRSA), consistent with a reduced hemolysis in the presence of bacteria. Mechanistically, temporin-1OLa rapidly killed MRSA by damaging bacterial membranes. Using micelles as a membrane-mimetic model, we determined the three-dimensional structure of temporin-1OLa by NMR spectroscopy. The peptide adopted a two-domain structure where a hydrophobic patch is followed by a classic amphipathic helix covering residues P3-I12. Such a structure is responsible for anti-biofilm ability in vitro and in vivo protection of wax moths Galleria mellonella from staphylococcal infection. Finally, our bioinformatic analysis leads to a classification of temporins into six types and confers significance to this NMR structure since temporin-1OLa shares a sequence model with 62% of temporins. Collectively, our results indicate the potential of temporin-1OLa as a new anti-MRSA compound, which shows an even better anti-biofilm capability in combination with linezolid.

Original languageEnglish (US)
Pages (from-to)9-20
Number of pages12
JournalPeptides
Volume106
DOIs
StatePublished - Aug 2018

Fingerprint

Bioinformatics
Computational Biology
Methicillin
Methicillin-Resistant Staphylococcus aureus
Peptides
Linezolid
Biofilms
Bacteria
temporin
Membranes
Staphylococcal Infections
Moths
Waxes
Gram-Positive Bacteria
Micelles
Hemolysis
Biological Products
Nuclear magnetic resonance spectroscopy
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance

Keywords

  • Antimicrobial peptides
  • Database
  • Galleria mellonella
  • MRSA
  • NMR
  • Staphylococcus aureus
  • Temporin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

Cite this

Antibacterial, antifungal, anticancer activities and structural bioinformatics analysis of six naturally occurring temporins. / Mishra, Biswajit; Wang, Xiuqing; Lushnikova, Tamara; Zhang, Yingxia; Golla, Radha M.; Narayana, Jayaram Lakshmaiah; Wang, Chunfeng; McGuire, Timothy R; Wang, Guangshun.

In: Peptides, Vol. 106, 08.2018, p. 9-20.

Research output: Contribution to journalArticle

Mishra, Biswajit ; Wang, Xiuqing ; Lushnikova, Tamara ; Zhang, Yingxia ; Golla, Radha M. ; Narayana, Jayaram Lakshmaiah ; Wang, Chunfeng ; McGuire, Timothy R ; Wang, Guangshun. / Antibacterial, antifungal, anticancer activities and structural bioinformatics analysis of six naturally occurring temporins. In: Peptides. 2018 ; Vol. 106. pp. 9-20.
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AU - Golla, Radha M.

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