Evaluation of a Novel Synthetic Peptide Derived from Cytolytic Mycotoxin Candidalysin

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.

Bithionol Restores Sensitivity of Multidrug-Resistant Gram-Negative Bacteria to Colistin with Antimicrobial and Anti-biofilm Effects

“…These biofilms can protect the embedded bacteria from environmental changes and antibiotic exposure . CV staining was used to perform biofilm-related tests in previous studies . Based on time-kill test strains, 4 additional bacteria strains of bacteria were included, and a total of 8 COL-R GNB strains were finally used for biofilm detection.…”

“…21 CV staining was used to perform biofilm-related tests in previous studies. 17 Based on time-kill test strains, 4 additional bacteria strains of bacteria were included, and a total of 8 COL-R GNB strains were finally used for biofilm detection. The absorbance (OD 595 nm) of the COL/BT combination group was significantly decreased compared with the control group and the BT or COL monotherapy groups (p < 0.05) (Figure 2), revealing that the combined drug group exhibited an inhibitory effect on the biofilm formation of strains.…”

“…Hence, the study investigated the antibacterial and anti-biofilm effects of the BT and COL combination against COL-R GNB (Klebsiella pneumoniae, A. baumannii, Escherichia coli, and Pseudomonas aeruginosa) in vitro and in vivo . The study also provided a novel and convenient antimicrobial strategy for the clinical treatment of infectious diseases caused by MDR, especially COL-R GNB.…”

Pathophysiology to Risk Factor and Therapeutics to Treatment Strategies on Epilepsy

“…Several studies focusing on the development of biopharmaceuticals with the potential to inhibit microglia are currently being carried out; for example, antimicrobial peptides with anti-inflammatory action are being investigated [81]. Ca-MAP1 is a multifunctional synthetic peptide with inhibitory action on microglia stimulated by LPS, rationally designed for use in an in vitro neuroinflammation model using BV-2 cell culture [82].…”