Evaluation of a Novel Synthetic Peptide Derived from Cytolytic Mycotoxin Candidalysin

Toxins (Basel). 2022 Oct 11;14(10):696. doi: 10.3390/toxins14100696.

Abstract

The importance of neuroinflammation in neurology is becoming increasingly apparent. In addition to neuroinflammatory diseases such as multiple sclerosis, the role of neuroinflammation has been identified in many non-inflammatory neurological disorders such as stroke, epilepsy, and cancer. The immune response within the brain involves the presence of CNS resident cells; mainly glial cells, such as microglia, the CNS resident macrophages. We evaluated the peptide Ca-MAP1 bioinspired on the C. albicans immature cytolytic toxin candidalysin to develop a less hemolytic peptide with anti-neuroinflammatory, antibacterial, and cytotoxic activity against tumor cells. In silico and in vitro studies were performed at various concentrations. Ca-MAP1 exhibits low hemolytic activity at lower concentrations and was not cytotoxic to MRC-5 and BV-2 cells. Ca-MAP1 showed activity against Acinetobacter baumannii, Escherichia coli ATCC, E. coli KPC, Klebsiella pneumoniae ATCC, Pseudomonas aeruginosa, and Staphylococcus aureus ATCC. Furthermore, Ca-MAP1 exhibits anti-neuroinflammatory activity in the BV-2 microglia model, with 93.78% inhibition of nitrate production at 18.1 µM. Ca-MAP1 presents cytotoxic activity against tumor cell line NCI-H292 at 36.3 μM, with an IC50 of 38.4 µM. Ca-MAP1 demonstrates results that qualify it to be evaluated in the next steps to promote the control of infections and provide an alternative antitumor therapy.

Keywords: Candida albicans; drug design; multiactivity peptide; neuroinflammation; peptide toxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Candida albicans
  • Escherichia coli*
  • Microbial Sensitivity Tests
  • Mycotoxins* / metabolism
  • Mycotoxins* / toxicity
  • Nitrates / metabolism
  • Peptides / chemistry
  • Pseudomonas aeruginosa

Substances

  • ECE1 protein, Candida albicans
  • Mycotoxins
  • Nitrates
  • Anti-Bacterial Agents
  • Peptides

Grants and funding

This work was supported by the Brazilian funding agencies CNPq, CAPES number 001, and FUNDECT.