Orit Malka1, Dorin Kalson1, Karin Yaniv2, Reut Shafir2, Manikandan Rajendran1, Oshrit Ben-David2, Ariel Kushmaro3,4, Michael M Meijler5,6, Raz Jelinek7,8. 1. Department of Chemistry, Ben-Gurion University of the Negev, 84105, Be'er Sheva, Israel. 2. Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, 84105, Be'er Sheva, Israel. 3. Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, 84105, Be'er Sheva, Israel. arielkus@bgu.ac.il. 4. National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, 84105, Be'er Sheva, Israel. arielkus@bgu.ac.il. 5. Department of Chemistry, Ben-Gurion University of the Negev, 84105, Be'er Sheva, Israel. meijler@bgu.ac.il. 6. National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, 84105, Be'er Sheva, Israel. meijler@bgu.ac.il. 7. Department of Chemistry, Ben-Gurion University of the Negev, 84105, Be'er Sheva, Israel. razj@bgu.ac.il. 8. Ilse Katz Institute for Nanoscale Science & Technology, Ben Gurion University of the Negev, 84105, Be'er Sheva, Israel. razj@bgu.ac.il.
Abstract
BACKGROUND: Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Co-existence of probiotic microorganisms are likely maintained via complex biomolecular mechanisms, secreted metabolites mediating cell-cell communication, and other yet-unknown biochemical pathways. In particular, deciphering molecular mechanisms by which probiotic microorganisms inhibit proliferation of pathogenic bacteria would be highly important for understanding both the potential benefits of probiotic foods as well as maintenance of healthy gut microbiome. RESULTS: The microbiome of a unique milk-fermented microorganism mixture was determined, revealing a predominance of the fungus Kluyveromyces marxianus. We further identified a new fungus-secreted metabolite-tryptophol acetate-which inhibits bacterial communication and virulence. We discovered that tryptophol acetate blocks quorum sensing (QS) of several Gram-negative bacteria, particularly Vibrio cholerae, a prominent gut pathogen. Notably, this is the first report of tryptophol acetate production by a yeast and role of the molecule as a signaling agent. Furthermore, mechanisms underscoring the anti-QS and anti-virulence activities of tryptophol acetate were elucidated, specifically down- or upregulation of distinct genes associated with V. cholerae QS and virulence pathways. CONCLUSIONS: This study illuminates a yet-unrecognized mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture. A newly identified fungus-secreted molecule-tryptophol acetate-was shown to disrupt quorum sensing pathways of the human gut pathogen V. cholerae. Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism co-existence in multi-population environments, such as probiotic foods and the gut microbiome. This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases. Video Abstract.
BACKGROUND: Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Co-existence of probiotic microorganisms are likely maintained via complex biomolecular mechanisms, secreted metabolites mediating cell-cell communication, and other yet-unknown biochemical pathways. In particular, deciphering molecular mechanisms by which probiotic microorganisms inhibit proliferation of pathogenic bacteria would be highly important for understanding both the potential benefits of probiotic foods as well as maintenance of healthy gut microbiome. RESULTS: The microbiome of a unique milk-fermented microorganism mixture was determined, revealing a predominance of the fungus Kluyveromyces marxianus. We further identified a new fungus-secreted metabolite-tryptophol acetate-which inhibits bacterial communication and virulence. We discovered that tryptophol acetate blocks quorum sensing (QS) of several Gram-negative bacteria, particularly Vibrio cholerae, a prominent gut pathogen. Notably, this is the first report of tryptophol acetate production by a yeast and role of the molecule as a signaling agent. Furthermore, mechanisms underscoring the anti-QS and anti-virulence activities of tryptophol acetate were elucidated, specifically down- or upregulation of distinct genes associated with V. cholerae QS and virulence pathways. CONCLUSIONS: This study illuminates a yet-unrecognized mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture. A newly identified fungus-secreted molecule-tryptophol acetate-was shown to disrupt quorum sensing pathways of the human gut pathogen V. cholerae. Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism co-existence in multi-population environments, such as probiotic foods and the gut microbiome. This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases. Video Abstract.
Authors: Damiana D Rosa; Manoela M S Dias; Łukasz M Grześkowiak; Sandra A Reis; Lisiane L Conceição; Maria do Carmo G Peluzio Journal: Nutr Res Rev Date: 2017-02-22 Impact factor: 7.800