Gene Networks Underlying the Resistance of Bifidobacterium longum to Inflammatory Factors

Veselovsky, Vladimir A.; Dyachkova, Marina S.; Menyailo, Egor; Polyaeva, Polina S.; Olekhnovich, Evgenii I.; Shitikov, Egor; Bespiatykh, Dmitry; Semashko, Tatiana A.; Kasianov, Artem S.; Ilina, Elena N.; Danilenko, V N; Klimina, Ksenia M.

doi:10.3389/fimmu.2020.595877

Cited by 8 publications

(6 citation statements)

References 52 publications

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“…433 It has been shown that bifidobacteria, in particular Bifidobacterium longum GT-15, can reduce intestinal inflammatory processes by producing the type-III fibronectin domain-containing protein (FN3) that binds to a pro-inflammatory agent such as tumor necrosis factor α TNFα. 434,435 The gut microbiome of people resistant to coronavirus infection is a promising source of Lactobacillus strains capable of producing peptides and other active metabolites that prevent the penetration of COVID-19 into human cells and decrease the severity and pathogenesis of this new coronavirus.…”

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confidence: 99%

Common Inflammatory Mechanisms in COVID-19 and Parkinson’s Diseases: The Role of Microbiome, Pharmabiotics and Postbiotics in Their Prevention

Даниленко¹,

Devyatkin²,

Марсова³

et al. 2021

JIR

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In the last decade, metagenomic studies have shown the key role of the gut microbiome in maintaining immune and neuroendocrine systems. Malfunction of the gut microbiome can induce inflammatory processes, oxidative stress, and cytokine storm. Dysfunction of the gut microbiome can be caused by short-term (virus infection and other infectious diseases) or long-term (environment, nutrition, and stress) factors. Here, we reviewed the inflammation and oxidative stress in neurodegenerative diseases and coronavirus infection (COVID-19). Here, we reviewed the renin-angiotensin-aldosterone system (RAAS) involved in the processes of formation of oxidative stress and inflammation in viral and neurodegenerative diseases. Moreover, the coronavirus uses ACE2 receptors of the RAAS to penetrate human cells. The coronavirus infection can be the trigger for neurodegenerative diseases by dysfunction of the RAAS. Pharmabiotics, postbiotics, and nextgeneration probiotics, are considered as a means to prevent oxidative stress, inflammatory processes, neurodegenerative and viral diseases through gut microbiome regulation.

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confidence: 99%

Common Inflammatory Mechanisms in COVID-19 and Parkinson’s Diseases: The Role of Microbiome, Pharmabiotics and Postbiotics in Their Prevention

Даниленко¹,

Devyatkin²,

Марсова³

et al. 2021

JIR

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“…It has been presumed that other species of bifidobacteria sustain cytokine homeostasis in the enteric immune system by binding other cytokines such as IL-6 and IL-beta. A recent study demonstrated how increasing concentration of TNF-α in the growth medium affects gene expression in bifidobacteria [89].…”

Section: Binding Of the Fn3 Protein Fragment To Cytokines (Tnf-α)mentioning

confidence: 99%

“…Using whole transcriptome analysis, the authors demonstrated that supplementation of B. longum GT15 culture medium with high concentration of the pro-inflammatory cytokine TNF-α (10 ng/mL) altered the expression of 1000 genes and 176 operons [89]. Many of the genes whose expression was significantly increased, among which was fn3, encoded proteins with antioxidant activity such as heat shock protein (hsp20) [90], glutathione [91], ABC transporters [92], enzymes involved in the metabolism of amino acids such as leucine, arginine [87], and short-chain fatty acids including propionate [93].…”

Section: Binding Of the Fn3 Protein Fragment To Cytokines (Tnf-α)mentioning

confidence: 99%

“…The FN3 protein is capable of specifically binding to TNF-α [22]. (B) The strain B.longum GT15 increases the expression of cytokines TNF-α, IL8 and IL10 in human cells [89]. Apparently, TNF-α interacts with an unknown signaling system of B. longum GT15 (possibly PKB2), triggering an increase in the expression of genes of the PFNA operon, including the fn3 gene [89].…”

Section: Binding Of the Fn3 Protein Fragment To Cytokines (Tnf-α)mentioning

confidence: 99%

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The Role of the PFNA Operon of Bifidobacteria in the Recognition of Host’s Immune Signals: Prospects for the Use of the FN3 Protein in the Treatment of COVID-19

Nezametdinova

Yunes

Dukhinova

et al. 2021

IJMS

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Bifidobacteria are some of the major agents that shaped the immune system of many members of the animal kingdom during their evolution. Over recent years, the question of concrete mechanisms underlying the immunomodulatory properties of bifidobacteria has been addressed in both animal and human studies. A possible candidate for this role has been discovered recently. The PFNA cluster, consisting of five core genes, pkb2, fn3, aaa-atp, duf58, tgm, has been found in all gut-dwelling autochthonous bifidobacterial species of humans. The sensory region of the species-specific serine-threonine protein kinase (PKB2), the transmembrane region of the microbial transglutaminase (TGM), and the type-III fibronectin domain-containing protein (FN3) encoded by the I gene imply that the PFNA cluster might be implicated in the interaction between bacteria and the host immune system. Moreover, the FN3 protein encoded by one of the genes making up the PFNA cluster, contains domains and motifs of cytokine receptors capable of selectively binding TNF-α. The PFNA cluster could play an important role for sensing signals of the immune system. Among the practical implications of this finding is the creation of anti-inflammatory drugs aimed at alleviating cytokine storms, one of the dire consequences resulting from SARS-CoV-2 infection.

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“…The expression of this gene (as well as other genes of the PFNA operon) increased as the strain B. longum subsp. longum GT15 was grown in the presence of TNFα [5]. The FN3 protein is found in most bifidobacteria and it contains a signal peptide, a transmembrane domain, and two FN3 domains [1][2][3][4].…”

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confidence: 99%

PFNA operon of bifidobacteria: Role of bioinformatics in the discovery, structural and functional characterization, and possible application in biotechnology

2022

The Thirteenth International Multiconference

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Motivation and Aim: PFNA (The acronym is formed by the initial letters of the three genes: pkb2, fn3, aaa-atp) cluster is widespread among Bifidobacterium strains [1][2][3][4]. The PFNA cluster, which was found to function as an operon in the strain B. longum subsp. longum GT15, is made up by genes encoding species-specific proteins, which diverge in homology between different bifidobacterial species [1][2][3][4]. It has been shown that this divergence resulted from positive selection likely exerted by the host immune system [3].One of the genes of the species specific PFNA operon, fn3, encodes a unique FN3 protein. The expression of this gene (as well as other genes of the PFNA operon) increased as the strain B. longum subsp. longum GT15 was grown in the presence of TNFα [5]. The FN3 protein is found in most bifidobacteria and it contains a signal peptide, a transmembrane domain, and two FN3 domains [1][2][3][4]. The presence of two FN3 domains in this protein containing motifs of cytokine receptor implied that this protein might be involved in binding cytokines produced by the host organism. An experiment devised and conducted previously demonstrated the ability of the protein fragment FN3 of B. longum subsp. longum GT15 to specifically bind to the human cytokine TNFα [6]. In this study, we further study the motifs of cytokine binding receptors in different species of bifidobacteria. Furthermore, non-synonymous substitutions (NSNP) in the sequenced genomes of strains of th species B. longum longum and B. longum infantis isolated from different populations were analyzed. The impact of the detected NSNPs on the 3D structures of the studied proteins was investigated. Methods and Algorithms: The NCBI (http://www.ncbi.nlm.nih.gov/) and UniProt (http://www.uniprot.org/) databases were used to search and identify genes/proteins; the trRosetta (https://yanglab.nankai.edu.cn/trRosetta/) and IntFOLD (version 5.0) (https://www.reading.ac.uk/bioinf/IntFOLD/IntFOLD5_form.html) programs to predict protein structures; the ProtParam (http://web.expasy.org/protparam/) program to calculate the molecular weight and isoelectric point of proteins. Results: The gut-dwelling species of bifidobacteria were found to display strong differences in the sequences of the studied motifs [7]. Analysis of NSNPs made it possible to divide them into several groups according to the geographical location of the human populations from which the strains were isolated. The detected NSNPs lead to significant changes in the 3D structures of the studied proteins [8]. Conclusion: It can be assumed that the revealed structural characteristics of the cytokine receptor motifs are related to the species-specific adaptations employed by bifidobacteria inhabiting different hosts and to the interspecies competition of different species of

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Gene Networks Underlying the Resistance of Bifidobacterium longum to Inflammatory Factors

Cited by 8 publications

References 52 publications

Common Inflammatory Mechanisms in COVID-19 and Parkinson’s Diseases: The Role of Microbiome, Pharmabiotics and Postbiotics in Their Prevention

Common Inflammatory Mechanisms in COVID-19 and Parkinson’s Diseases: The Role of Microbiome, Pharmabiotics and Postbiotics in Their Prevention

The Role of the PFNA Operon of Bifidobacteria in the Recognition of Host’s Immune Signals: Prospects for the Use of the FN3 Protein in the Treatment of COVID-19

PFNA operon of bifidobacteria: Role of bioinformatics in the discovery, structural and functional characterization, and possible application in biotechnology

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