XENOFOOD-An Autoclaved Feed Supplement Containing Autoclavable Antimicrobial Peptides-Exerts Anticoccidial GI Activity, and Causes Bursa Enlargement, but Has No Detectable Harmful Effects in Broiler Cockerels despite In Vitro Detectable Cytotoxicity on LHM Cells

András Fodor; Tibor Vellai; Claudia Hess; László Makrai; Károly Dublecz; László Pál; Andor Molnár; Michael G Klein; Eustachio Tarasco; Sándor Józsa; Petra Ganas; Michael Hess

doi:10.3390/pathogens12030458

XENOFOOD-An Autoclaved Feed Supplement Containing Autoclavable Antimicrobial Peptides-Exerts Anticoccidial GI Activity, and Causes Bursa Enlargement, but Has No Detectable Harmful Effects in Broiler Cockerels despite In Vitro Detectable Cytotoxicity on LHM Cells

Pathogens. 2023 Mar 14;12(3):458. doi: 10.3390/pathogens12030458.

Authors

Affiliations

¹ Department of Genetics, Eötvös Loránd University, Pázmány P. Sétány 1C, H-1117 Budapest, Hungary.
² Clinic for Poultry and Fish Medicine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine (Vetmeduni Vienna), 1210 Vienna, Austria.
³ Department of Microbiology and Infectious Diseases, University of Veterinary Medicine, H-1581 Budapest, Hungary.
⁴ Institute of Physiology and Nutrition, Georgikon Campus, Hungarian University of Agriculture and Life Sciences (MATE), Deák Ferenc utca 16, H-8360 Keszthely, Hungary.
⁵ USDA-ARS & Department of Entomology, The Ohio State University, 13416 Claremont Ave., Cleveland, OH 44130, USA.
⁶ Department of Soil, Plant and Food Sciences, University of Bari "Aldo Moro", Via Amendola 165/A, 70126 Bari, Italy.

Abstract

Entomopathogenic bacteria are obligate symbionts of entomopathogenic nematode (EPN) species. These bacteria biosynthesize and release non-ribosomal-templated hybrid peptides (NR-AMPs), with strong, and large-spectral antimicrobial potential, capable of inactivating pathogens belonging to different prokaryote, and eukaryote taxa. The cell-free conditioned culture media (CFCM) of Xenorhabdus budapestensis and X. szentirmaii efficiently inactivate poultry pathogens like Clostridium, Histomonas, and Eimeria. To learn whether a bio-preparation containing antimicrobial peptides of Xenorhabdus origin with accompanying (in vitro detectable) cytotoxic effects could be considered a safely applicable preventive feed supplement, we conducted a 42-day feeding experiment on freshly hatched broiler cockerels. XENOFOOD (containing autoclaved X. budapestensis, and X. szentirmaii cultures developed on chicken food) were consumed by the birds. The XENOFOOD exerted detectable gastrointestinal (GI) activity (reducing the numbers of the colony-forming Clostridium perfringens units in the lower jejunum. No animal was lost in the experiment. Neither the body weight, growth rate, feed-conversion ratio, nor organ-weight data differed between the control (C) and treated (T) groups, indicating that the XENOFOOD diet did not result in any detectable adverse effects. We suppose that the parameters indicating a moderate enlargement of bursas of Fabricius (average weight, size, and individual bursa/spleen weight-ratios) in the XENOFOOD-fed group must be an indirect indication that the bursa-controlled humoral immune system neutralized the cytotoxic ingredients of the XENOFOOD in the blood, not allowing to reach their critical cytotoxic concentration in the sensitive tissues.

Keywords: CFCM (cell-free conditioned media); Clostridium CFU—(colony forming unit); EPB (entomo-pathogenic bacteria, Xenorhabdus, (X. budapestensis, X. szentirmaii, X. innexii), and Photorhabdus species); MDR; NR-AMP (non-ribosomal-templated antimicrobial peptides); XENOFOOD; alternative antibiotics; anti-bacterial; anti-coccidial; anti-microbial; anti-protist activity; cytotoxicity; in situ (local) bioavailability; multidrug resistance.

Grants and funding

This research received no external funding, except for some parts of this study (The in vitro Clostridium bioassays preceding XENOFOOD experiments) were supported by the TÁMOP-4.2.2/B-10/1-2010-0025 project based on the financial support the State of Hungary and the EU. The chicken feeding experiments included two (control (34, chicken)) and a XENOFOOD-fed (34 chicken) group of another feeding experiment of the respective Department of the University of used-to-be Pannonia, Keszthely, Hungary, (recently a joint unit of the Hungarian University of Agriculture and Life Sciences (MATE).