Exploring interplay between bovine milk-derived α-lactalbumin, pathogenic bacteria, and bacteriophages at the molecular interface of inflammation

Darab Ghadimi; Aysel Şahi N Kaya; Sandra Krüger; Christoph Röcken; Heiner Schäfer; Jumpei Uchiyama; Shigenobu Matsuzaki; Wilhelm Bockelmann

doi:10.1016/j.cimid.2024.102271

Exploring interplay between bovine milk-derived α-lactalbumin, pathogenic bacteria, and bacteriophages at the molecular interface of inflammation

Comp Immunol Microbiol Infect Dis. 2024 Oct 28:115:102271. doi: 10.1016/j.cimid.2024.102271. Online ahead of print.

Authors

Darab Ghadimi¹, Aysel Şahi N Kaya², Sandra Krüger³, Christoph Röcken³, Heiner Schäfer⁴, Jumpei Uchiyama⁵, Shigenobu Matsuzaki⁶, Wilhelm Bockelmann⁷

Affiliations

¹ Department of Microbiology and Biotechnology, Max Rubner-Institut, Hermann-Weigmann-Str 1, Kiel D-24103, Germany. Electronic address: darab.ghadimi@mri.bund.de.
² Department of Nutrition and Dietetics, Faculty of Health Sciences, Antalya Bilim University, Antalya, Turkey.
³ Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein, Arnold-Heller-Straße 3/14, Kiel D-24105, Germany.
⁴ Laboratory of Molecular Gastroenterology & Hepatology, Christian-Albrechts-University & UKSH Campus Kiel, Kiel 24105, Germany.
⁵ Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
⁶ Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University, Kochi, Japan.
⁷ Department of Microbiology and Biotechnology, Max Rubner-Institut, Hermann-Weigmann-Str 1, Kiel D-24103, Germany.

PMID: 39489117
DOI: 10.1016/j.cimid.2024.102271

Abstract

There is so far no available data about how the additive, synergistic, or antagonistic effects of the combined form of alpha-lactalbumin (α-La) and bacteriophages might modulate the cellular milieu of the host-pathogen interface. A co-culture of colonocytes and hepatocytes was stimulated with Pseudomonas aeruginosa PAO1 in the presence of KPP22 phage and incubated for 6 hours in medium alone or medium supplemented with bovine milk-origin α-La. The combination of KPP22 phage and α-La significantly inhibited P.a PAO1-elicited secretion of IL-1β, IL-6, and ICAM-1, which are the mediators and enzymes associated with the inflammatory response to an infectious-inflamed milieu. Cell viability was higher in the P.a PAO1+ KPP22 phage group compared to the P.a PAO1alone group. KPP22 phage and α-La, either alone or in combination, rescued P.a PAO1-induced aberrant PGE1/PGE2 production ratios. The convergence of ingested α-La and phages mitigates pro-inflammatory mediators. α-La leads to an increased sensitivity of opportunistic pathogenic bacteria to phages. Structural, functional, or immunological similarities between ingested α-La and phages play an important role in the mitigation of infection-driven pathobiological processes.

Keywords: Bacteriophages; Cytokine; Infection; Inflammation; α-Lactalbumin.