Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Antimicrobial Peptides for Combating Eukaryotic Pathogens: Anti-Histomonal, and Anti-Leishmanial Potential of Antimicrobial Peptides Released by Entomopathogenic Nematode Symbiont Bacteria

András Fodor
* ORCID logo ,
Claudia Hess
ORCID logo ,
Petra Ganas
,
Zsófia Boros
,
János Kiss
,
László Makrai
,
Károly Dublecz
ORCID logo ,
László Pál
ORCID logo ,
László Fodor
ORCID logo ,
Anna Sebestyén
,
Michael G. Klein
,
Eustachio Tarasco
ORCID logo ,
Manjusha M. Kulkarni
,
Bradford S. McGwire
,
Tibor Vellai
,
Michael Hess
* ORCID logo
Version 1 : Received: 1 August 2023 / Approved: 2 August 2023 / Online: 3 August 2023 (09:39:00 CEST)

A peer-reviewed article of this Preprint also exists.

Fodor, A.; Hess, C.; Ganas, P.; Boros, Z.; Kiss, J.; Makrai, L.; Dublecz, K.; Pál, L.; Fodor, L.; Sebestyén, A.; Klein, M.G.; Tarasco, E.; Kulkarni, M.M.; McGwire, B.S.; Vellai, T.; Hess, M. Antimicrobial Peptides (AMP) in the Cell-Free Culture Media of Xenorhabdus budapestensis and X. szentirmaii Exert Anti-Protist Activity against Eukaryotic Vertebrate Pathogens including Histomonas meleagridis and Leishmania donovani Species. Antibiotics 2023, 12, 1462. Fodor, A.; Hess, C.; Ganas, P.; Boros, Z.; Kiss, J.; Makrai, L.; Dublecz, K.; Pál, L.; Fodor, L.; Sebestyén, A.; Klein, M.G.; Tarasco, E.; Kulkarni, M.M.; McGwire, B.S.; Vellai, T.; Hess, M. Antimicrobial Peptides (AMP) in the Cell-Free Culture Media of Xenorhabdus budapestensis and X. szentirmaii Exert Anti-Protist Activity against Eukaryotic Vertebrate Pathogens including Histomonas meleagridis and Leishmania donovani Species. Antibiotics 2023, 12, 1462.

Abstract

Antimicrobial peptides provide a powerful toolkit for combating multidrug resistance. Combatting eukaryotic pathogens is complicated by the fact, the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria, (symbionts of entomopathogenic nematode species), release a series of non-ribosomal templated antimicrobial peptides, some may be potential drug candidates. The ability of an entomopathogenic nematode /entomopathogenic bacterium symbiotic complex to survive in a given polyxenic milieu is a coevolutionary product, explaining that those gene complexes which are responsible for the biosynthesis of different non-ribosomal templated antimicrobial protective peptides (including those which are potently capable to inactivate the protist mammalian -pathogen Leishmania and the gallinaceous bird pathogen Histomonas) are co-regulated. Our approach is based on comparative antimicrobial bioassays of the culture media of the wild-type and regulatory mutant strains. We concluded that Xenorhabdus budapestensis and X. szentirmaii are excellent sources of non-ribosomal templated antimicrobial peptides, that are efficient antagonists of the mentioned pathogens. Data on selective cytotoxicity of different cell-free culture media encourages us to forecast that the recently discovered “easy-PACId” research strategy is suitable for constructing EPB strains producing and releasing single, harmless, non-ribosomal templated antimicrobial peptides with considerable drug, (probiotic) -candidate potential.

Keywords

non-ribosomal antimicrobial peptides (NR-AMP); entomopathogenic nematode-symbiont bacteria (EPB); Xenorhabdus; (X. budapestensis; X. szentirmaii; X. innexii); Photorhabdus (P. luminescens TT01); CFCM; (cellfree conditioned culture media); intracellular mammalian parasite; Leishmania; extracellular avian pathogens; Histomonas; probiotic potential

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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