<i>Limosilactobacillus fermentum</i> Strain 3872: Antibacterial and Immunoregulatory Properties and Synergy with Prebiotics against Socially Significant Antibiotic-Resistant Infections of Animals and Humans
Vyacheslav M. Abramov,
Igor V. Kosarev,
Andrey V. Machulin,
Tatiana V. Priputnevich,
Irina O. Chikileva,
Evgenia I. Deryusheva,
Tatiana N. Abashina,
Almira D. Donetskova,
Alexander N. Panin,
Vyacheslav G. Melnikov,
Nataliya E. Suzina,
Ilia N. Nikonov,
Marina V. Selina,
Valentin S. Khlebnikov,
Vadim K. Sakulin,
Raisa N. Vasilenko,
Vladimir A. Samoilenko,
Vladimir N. Uversky,
Andrey V. Karlyshev
Affiliations
Vyacheslav M. Abramov
Federal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor), Federal State Budgetary Institution “The Russian State Center for Animal Feed and Drug Standardization and Quality” (FGBU VGNKI), 123022 Moscow, Russia
Igor V. Kosarev
Federal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor), Federal State Budgetary Institution “The Russian State Center for Animal Feed and Drug Standardization and Quality” (FGBU VGNKI), 123022 Moscow, Russia
Andrey V. Machulin
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, Russia
Tatiana V. Priputnevich
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health, 117997 Moscow, Russia
Irina O. Chikileva
Laboratory of Cell Immunity, Blokhin National Research Center of Oncology, Ministry of Health RF, 115478 Moscow, Russia
Evgenia I. Deryusheva
Institute for Biological Instrumentation, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, Russia
Tatiana N. Abashina
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, Russia
Almira D. Donetskova
NRC Institute of Immunology FMBA of Russia, 115522 Moscow, Russia
Alexander N. Panin
Federal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor), Federal State Budgetary Institution “The Russian State Center for Animal Feed and Drug Standardization and Quality” (FGBU VGNKI), 123022 Moscow, Russia
Vyacheslav G. Melnikov
Gabrichevsky Research Institute for Epidemiology and Microbiology, 125212 Moscow, Russia
Nataliya E. Suzina
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, Russia
Ilia N. Nikonov
Federal State Educational Institution of Higher Professional Education, Moscow State Academy of Veterinary Medicine and Biotechnology named after K.I. Skryabin, 109472 Moscow, Russia
Marina V. Selina
Federal State Educational Institution of Higher Professional Education, Moscow State Academy of Veterinary Medicine and Biotechnology named after K.I. Skryabin, 109472 Moscow, Russia
Valentin S. Khlebnikov
Institute of Immunological Engineering, 142380 Lyubuchany, Russia
Vadim K. Sakulin
Institute of Immunological Engineering, 142380 Lyubuchany, Russia
Raisa N. Vasilenko
Institute of Immunological Engineering, 142380 Lyubuchany, Russia
Vladimir A. Samoilenko
Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center “Pushchino Scientific Center for Biological Research of Russian Academy of Science”, Russian Academy of Science, 142290 Pushchino, Russia
Vladimir N. Uversky
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
Andrey V. Karlyshev
Department of Biomolecular Sciences, Faculty of Health, Science, Social Care and Education, Kingston University London, Kingston upon Thames KT1 2EE, UK
Limosilactobacillus fermentum strain 3872 (LF3872) was originally isolated from the breast milk of a healthy woman during lactation and the breastfeeding of a child. The high-quality genome sequencing of LF3872 was performed, and a gene encoding a unique bacteriocin was discovered. It was established that the bacteriocin produced by LF3872 (BLF3872) belongs to the family of cell-wall-degrading proteins that cause cell lysis. The antibacterial properties of LF3872 were studied using test cultures of antibiotic-resistant Gram-positive and Gram-negative pathogens. Gram-positive pathogens (Staphylococcus aureus strain 8325-4 and S. aureus strain IIE CI-SA 1246) were highly sensitive to the bacteriolytic action of LF3872. Gram-negative pathogens (Escherichia coli, Salmonella strains, and Campylobacter jejuni strains) were more resistant to the bacteriolytic action of LF3872 compared to Gram-positive pathogens. LF3872 is a strong co-aggregator of Gram-negative pathogens. The cell-free culture supernatant of LF3872 (CSLF3872) induced cell damage in the Gram-positive and Gram-negative test cultures and ATP leakage. In the in vitro experiments, it was found that LF3872 and Actigen prebiotic (Alltech Inc., Nicholasville, KY, USA) exhibited synergistic anti-adhesive activity against Gram-negative pathogens. LF3872 has immunoregulatory properties: it inhibited the lipopolysaccharide-induced production of proinflammatory cytokines IL-8, IL-1β, and TNF-α in a monolayer of Caco-2 cells; inhibited the production of IL-12 and stimulated the production of IL-10 in immature human dendritic cells; and stimulated the production of TGF-β, IFN-γ, and IgA in the immunocompetent cells of intestinal Peyer’s patches (PPs) in mice. These results indicate the possibility of creating a synbiotic based on LF3872 and a prebiotic derived from Saccharomyces cerevisiae cell wall components. Such innovative drugs and biologically active additives are necessary for the implementation of a strategy to reduce the spread of antibiotic-resistant strains of socially significant animal and human infections.
