Rondonin: antimicrobial properties and mechanism of action

• Published in: FEBS open bio Vol. 11; no. 9; pp. 2541 - 2559
• Main Authors: Riciluca, Katie C. T., Oliveira, Ursula C., Mendonça, Ronaldo Z., Bozelli Junior, José C., Schreier, Shirley, Silva Junior, Pedro I.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-09-2021; John Wiley and Sons Inc; Wiley
• Subjects: Amino acid sequence; Animals; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antibiotics; Antifungal activity; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; antifungal peptide; Antimicrobial agents; Antimicrobial peptides; Antimicrobial Peptides - chemistry; Antimicrobial Peptides - pharmacology; antiviral; Antiviral activity; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; C-Terminus; Candida - drug effects; Cell Line; Cell Survival - drug effects; Competition; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA binding; Fungi; hemocyanin; Humans; Hydrogen-Ion Concentration; Immune system; Infectious diseases; Invertebrates; Laboratories; Mammalian cells; Measles; Microbial Sensitivity Tests; Microbiota; Microorganisms; Pathogens; Peptides; pH effects; RNA viruses; rondonin; Vagina; China; rondonin; antifungal peptide; DNA binding; antiviral; hemocyanin
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1002/2211-5463.13253

Infectious diseases are among the major causes of death in the human population. A wide variety of organisms produce antimicrobial peptides (AMPs) as part of their first line of defense. A peptide from Acanthoscurria rondoniae plasma, rondonin—with antifungal activity, a molecular mass of 1236 Da and primary sequence IIIQYEGHKH—was previously studied (UniProt accession number B3EWP8). It showed identity with the C terminus of subunit ‘D’ of the hemocyanin of the Aphonopelma hentzi spider. This result led us to propose a new pathway of the immune system of arachnids that suggests a new function to hemocyanin: production of antimicrobial peptides. Rondonin does not interact with model membranes and was able to bind to yeast nucleic acids but not bacteria. It was not cytotoxic against mammalian cells. The antifungal activity of rondonin is pH‐dependent and peaks at pH ˜ 4–5. The peptide presents synergism with gomesin (spider hemocyte antimicrobial peptide—UniProtKB—P82358) against human yeast pathogens, suggesting a new potential alternative treatment option. Antiviral activity was detected against RNA viruses, measles, H1N1, and encephalomyocarditis. This is the first report of an arthropod hemocyanin fragment with activity against human viruses. Currently, it is vital to invest in the search for natural and synthetic antimicrobial compounds that, above all, present alternative mechanisms of action to first‐choice antimicrobials.
Rondonin's mechanism of action suggests yeast DNA/RNA binding, as it does not cause membrane disturbance. It acts synergistically with gomesin. It has superior action at pH 4 ˜ 5, and antiviral activity was detected against RNA viruses. This is the first report of an arthropod hemocyanin fragment with activity against human viruses.