Rondonin: antimicrobial properties and mechanism of action

Abstract

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 1,236 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.

Molecules with antimicrobial activity in the secretion of the arthrodial membrane gland of a harvester (Arachnida, Opiliones)

“…In a recent work, we demonstrated that the arthrodial membrane of the harvester Mischonyx squalidus (Arachnida, Opiliones) shows features of secretory activity such as pores and cuticular canals, secretory cells with mitochondria, smooth endoplasmic reticulum and secretory granules [Silva et al 2021, unpublished data]. Furthermore, we demonstrated that the secretions of these secretory cells include proteins and oils [Silva et al 2021]. In view of this evidence and based on the literature, we suggest that the arthrodial membrane has a gland with a lubricating function at least in the studied leg joint of leg IV [Silva et al 2021, unpublished data].…”

“…The proteomic analysis of the content of the secretory cells in the AM revealed similarities with proteins, speci cally with peptides with antimicrobial activity [Silva et al 2021], whose activity has now been demonstrated. Moreover, both fractions have antimicrobial activity at low concentrations, which is important from a pharmacological point of view (Nascimento et al 2016;Diniz et al 2018;Diaz-Roa et al 2018, 2019.…”

“…A number of papers describe antimicrobial molecules in setae, venom, secretions, hemolymph (hemocytes and plasma) and body extracts in arthropods, including arachnids (Riciluca et al 2021;Chaparro & Silva-Junior 2016;Diaz-Roa et al 2018;Segura-Ramírez & Silva-Junior 2018). In harvesters, Sayegh et al (2016) found an AMP (longipin) in the hemolymph of Acutisoma longipes (Opiliones, Gonyleptidae) that has antifungal activity.…”

“…The function of the other proteins remains unknown, but Silva et al (2021) found molecules putatively homologous to peptides and/or proteins with functions such as cellular metabolism, signaling and binding and defense. We also do not know the mechanisms through which the peptides act, but they usually either break the cell membrane or interact with internal components of the bacterium cell (Ben eld and Henriques 2020).…”

Antimicrobial Mechanisms and Clinical Application Prospects of Antimicrobial Peptides

“…PR-39, an AMP isolated from the upper half of the pig's small intestine, kills bacteria by preventing the synthesis of proteins and DNA and causing the degradation of these components [116]. Other AMPs that can interact with nucleic acids include human neutrophil peptide (HNP)-1 [117], porcine β-defensin 2 (pBD2) [118,119] and rondonin [120];…”