Genome Features of Probiotic Bifidobacteria Determining Their Strain-Specific Properties

A G Tochilina; I V Belova; T N Ilyicheva; V Yu Marchenko; V A Zhirnov; S B Molodtsova; A V Ikonnikov; I V Muhkina; A S Blagonravova; I V Soloveva

doi:10.17691/stm2022.14.5.04

Genome Features of Probiotic Bifidobacteria Determining Their Strain-Specific Properties

Sovrem Tekhnologii Med. 2022;14(5):36-43. doi: 10.17691/stm2022.14.5.04. Epub 2022 Sep 29.

Authors

Affiliations

¹ Senior Researcher, Laboratory of Human Microbiome and Means of Its Correction; Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology of Rospotrebnadzor (Russian Federal Consumer Rights Protection and Human Health Control Service), 71 Malaya Yamskaya St., Nizhny Novgorod, 603950, Russia; Associate Professor, Department of Epidemiology, Microbiology and Evidence-Based Medicine; Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Square, Nizhny Novgorod, 603005, Russia.
² Leading Researcher, Laboratory of Human Microbiome and Means of Its Correction; Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology of Rospotrebnadzor (Russian Federal Consumer Rights Protection and Human Health Control Service), 71 Malaya Yamskaya St., Nizhny Novgorod, 603950, Russia; Associate Professor, Department of Epidemiology, Microbiology and Evidence-Based Medicine; Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Square, Nizhny Novgorod, 603005, Russia.
³ Leading Researcher, Department of Zoonotic Infections and Influenza; State Research Center of Virology and Biotechnology "Vector" of Rospotrebnadzor, Koltsovo, Novosibirsk Region, 630559, Russia.
⁴ Researcher, Laboratory of Human Microbiome and Means of Its Correction; Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology of Rospotrebnadzor (Russian Federal Consumer Rights Protection and Human Health Control Service), 71 Malaya Yamskaya St., Nizhny Novgorod, 603950, Russia.
⁵ Research Assistant; Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Square, Nizhny Novgorod, 603005, Russia.
⁶ Professor, Director of the Institute of Fundamental Medicine; Head of the Department of Normal Physiology named after N.Y. Belenkov; Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Square, Nizhny Novgorod, 603005, Russia.
⁷ Head of the Department of Clinical Laboratory Diagnostics; Professor, Department of Epidemiology, Microbiology and Evidence-Based Medicine; Vice-Rector for Science; Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Square, Nizhny Novgorod, 603005, Russia.
⁸ Associate Professor, Leading Researcher, Head of the Laboratory of Human Microbiome and Means of its Correction; Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology of Rospotrebnadzor (Russian Federal Consumer Rights Protection and Human Health Control Service), 71 Malaya Yamskaya St., Nizhny Novgorod, 603950, Russia.

Abstract

The aim of the study was to analyze the genome features of the probiotic strains Bifidobacterium longum 379, Bifidobacterium bifidum 1, and Bifidobacterium bifidum 791 and study their antiviral activity.

Materials and methods: Whole genome sequencing of three strains of bifidobacteria was performed on the MiSeq platform (Illumina Inc., USA). The genomes were annotated using the Prokka v. 1.11 utility and RAST genomic server. The individual genetic determinants were searched using the ResFinder 3.2, PathogenFinder, PlasmidFinder, RAST, and Bagel 4 software. The antiviral activity of the strains against influenza A viruses was studied using MDCK cells (Madin-Darby canine kidney cells), the epidemic strain of influenza A/Lipetsk/1V/2018 (H1N1 pdm09) (EPI_ISL_332798), the highly pathogenic avian influenza virus A/common gull/Saratov/1676/2018 (H5N6) strain (EPI_ISL_336925), and neutral red vital dye.

Results: The genomes of all studied strains contained determinants responsible for utilization of carbohydrates of plant origin; the genes of key enzymes for the synthesis of tryptophan and folic acid are present in the genomes of B. longum 379 and B. bifidum 791. A feature of the B. bifidum 791 genome is the presence of determinants responsible for the synthesis of thermostable type I bacteriocins - flavucin and lasso peptide. The B. bifidum 791 strain was found to show pronounced antiviral activity against both the strains of influenza A, the supernatant of which suppressed viral replication in vitro up to a dilution of 1:8, and the cells inhibited viral reproduction up to a concentration of 6·106 CFU/ml.

Conclusion: The analysis of complete genomes of B. longum 379, B. bifidum 1, and B. bifidum 791 showed features that determine their strain-specific properties, the findings on which were previously made empirically based on indirect signs. In the genomes of B. longum 379 and B. bifidum 791 strains, in contrast to B. bifidum 1 strain, key enzymes for the synthesis of tryptophan and folic acid were found. These substances have an impact on the human body in many ways, including having a thymoleptic effect (reducing emotional stress, irritability, anxiety, eliminating lethargy, apathy, melancholy, anxiety) and regulating cognitive activity. The presence of determinants responsible for the synthesis of thermostable type I bacteriocins in the genome of B. bifidum 791 strain determines its pronounced antiviral activity.

Keywords: Bifidobacterium; antiviral activity; influenza A virus; probiotics; whole genome sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents
Bacteriocins*
Bifidobacterium / genetics
Bifidobacterium bifidum* / physiology
Dogs
Folic Acid
Humans
Influenza A Virus, H1N1 Subtype*
Influenza, Human*
Probiotics* / pharmacology
Tryptophan

Substances

Tryptophan
Bacteriocins
Antiviral Agents
Folic Acid

Grants and funding

Study funding. The study was conducted as part of the industry research program 2021–2025 “Scientific support of epidemiological surveillance and sanitary protection of the territory of the Russian Federation. Creation of new technologies, means and methods of control and prevention of infectious and parasitic diseases”, research topic No.21091400194-0.