Secreted Akkermansia muciniphila threonyl-tRNA synthetase functions to monitor and modulate immune homeostasis

Kim, Su-Man; Park, Shinhye; Hwang, Seung-Ho; Lee, Eun Young; Kim, Jong Hwan; Lee, Ga Seul; Lee, Gil Jae; Chang, Dong-Ho; Lee, Jae-Geun; Hwang, Jungwon; Lee, Youngjin; Kyung, Minsoo; Kim, Eunkyoung; Kim, Jae-Hoon; Kim, Tae‐Hwan; Moon, Jeong Hee; Kim, Byoung-Chan; Ko, GwangPyo; Kim, Seon‐Young; Ryu, Ji-Hwan; Lee, Jeong-Soo; Lee, Chul‐Ho; Kim, Jeong‐Yoon; Kim, Sung Hoon; Lee, Won–Jae; Kim, Myung Hee

doi:10.1016/j.chom.2023.05.007

Cited by 35 publications

(21 citation statements)

References 103 publications

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“…Several proteins from A. muciniphila, including Amuc1100, P9, and AmTARS, have exhibited pronounced positive effects on human health. Amuc1102, in particular, which belongs to the Amuc1100 operon, has a predicted SP sequence (Table ) and a folding structure similar to immunoglobulin, hinting at its potential secretion and role as an actuator protein, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…8−11 Escherichia coli Nissle 1917 and lactic acid bacteria are frequently chosen strains for these purposes. 5,8,12,13 However, the Bacteroides genus, a commensal bacteria group, is gaining interest due to its superior colonization stability, making it an emerging candidate for live biotherapeutics. 6,14 Among them, Bacteroides thetaiotaomicron, a prevalent species in the human gut microbiome, demonstrates a unique ability to digest a diverse range of polysaccharides, including starch and pectin from various sources.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Of these, bacteria stand out as particularly promising vehicles, especially for applications in human health . Using bacteria, significant research has been directed toward engineering probiotics to provide health benefits such as mitigating genetic disorders, controlling Crohn’s disease, inhibiting pathogen growth, and reducing the risk of colorectal cancer. − Escherichia coli Nissle 1917 and lactic acid bacteria are frequently chosen strains for these purposes. ,,, However, the Bacteroides genus, a commensal bacteria group, is gaining interest due to its superior colonization stability, making it an emerging candidate for live biotherapeutics. , Among them, Bacteroides thetaiotaomicron, a prevalent species in the human gut microbiome, demonstrates a unique ability to digest a diverse range of polysaccharides, including starch and pectin from various sources. − This capability is attributed to enzymes responsible for 88 polysaccharide utilization loci . Additionally, B.…”

Section: Introductionmentioning

confidence: 99%

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Novel Signal Peptides and Episomal Plasmid System for Enhanced Protein Secretion in Engineered Bacteroides Species

Kim,

Ju,

Kim

et al. 2024

ACS Synth. Biol.

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The genus Bacteroides, a predominant group in the human gut microbiome, presents significant potential for microbiome engineering and the development of live biotherapeutics aimed at treating gut diseases. Despite its promising capabilities, tools for effectively engineering Bacteroides species have been limited. In our study, we have made a breakthrough by identifying novel signal peptides in Bacteroides thetaiotaomicron and Akkermansia muciniphila. These peptides facilitate efficient protein transport across cellular membranes in Bacteroides, a critical step for therapeutic applications. Additionally, we have developed an advanced episomal plasmid system. This system demonstrates superior protein secretion capabilities compared to traditional chromosomal integration plasmids, making it a vital tool for enhancing the delivery of therapeutic proteins in Bacteroides species. Initially, the stability of this episomal plasmid posed a challenge; however, we have overcome this by incorporating an essential gene-based selection system. This novel strategy not only ensures plasmid stability but also aligns with the growing need for antibiotic-free selection methods in clinical settings. Our work, therefore, not only provides a more robust secretion system for Bacteroides but also sets a new standard for the development of live biotherapeutics.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel Signal Peptides and Episomal Plasmid System for Enhanced Protein Secretion in Engineered Bacteroides Species

Kim,

Ju,

Kim

et al. 2024

ACS Synth. Biol.

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“…A recent study has reported that Akkermansia can monitor and regulate immune homeostasis through the secretion of threonyl−tRNA synthetase (Am TARS). 27 Desulfovibrio is closely associated with inflammation, increasing intestinal permeability and host inflammatory responses, which can exacerbate atherosclerosis. 28 Similarly, an increased abundance of Colidextribacter has been associated with impaired intestinal barrier function.…”

Section: ■ Discussionmentioning

confidence: 99%

“…The upregulation of the biosynthetic pathway of ammonia–tRNA in metabolism may be associated with increased abundance of Akkermansia. A recent study has reported that Akkermansia can monitor and regulate immune homeostasis through the secretion of threonyl–tRNA synthetase (Am TARS) Desulfovibrio is closely associated with inflammation, increasing intestinal permeability and host inflammatory responses, which can exacerbate atherosclerosis .…”

Section: Discussionmentioning

confidence: 99%

Antiaging Effects of Human Fecal Transplants with Different Combinations of Bifidobacterium bifidum LTBB21J1 and Lactobacillus casei LTL1361 in d-Galactose-Induced Mice

Zhou,

Zhang,

Zheng

et al. 2024

J. Agric. Food Chem.

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The feces of healthy middle-aged and old people were first transplanted into D-galactose-induced aging mice to construct humanized aging mice with gut microbiota (FMTC) to confirm the antiaging effect of probiotics produced from centenarians. The mouse model was then treated with centenarian-derived Bifidobacterium bifidum (FMTL), Lactobacillus casei (FMTB), and their mixtures (FMTM), and young mice were used as the control. Compared with the FMTC group, the results demonstrated that the probiotics and their combinations alleviated neuronal damage, increased antioxidant capacity, decreased inflammation, and enhanced cognitive and memory functions in aging mice. In the gut microbiota, the relative abundance of Lactobacillus, Ligilactobacillus, and Akkermansia increased and that of Desulfovibrio and Colidextribacter decreased in the FMTM group compared with that in the FMTC group. The three probiotic groups displayed significant changes in 15 metabolites compared with the FMTC group, with 4 metabolites showing increased expression and 11 metabolites showing decreased expression. The groups were graded as Control > FMTM > FMTB > FMTL > FMTC using a newly developed comprehensive quantitative scoring system that thoroughly analyzed the various indicators of this study. The beneficial antiaging effects of probiotics derived from centenarians were quantitatively described using a novel perspective in this study; it is confirmed that both probiotics and their combinations exert antiaging effects, with the probiotic complex group exhibiting a larger effect.

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Effects of modified-BHI medium on the growth and metabolites of Akkermansia muciniphila

Zhang,

Zhou,

et al. 2024

Food Sci Biotechnol

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Secreted Akkermansia muciniphila threonyl-tRNA synthetase functions to monitor and modulate immune homeostasis

Cited by 35 publications

References 103 publications

Novel Signal Peptides and Episomal Plasmid System for Enhanced Protein Secretion in Engineered Bacteroides Species

Novel Signal Peptides and Episomal Plasmid System for Enhanced Protein Secretion in Engineered Bacteroides Species

Antiaging Effects of Human Fecal Transplants with Different Combinations of Bifidobacterium bifidum LTBB21J1 and Lactobacillus casei LTL1361 in d-Galactose-Induced Mice

Effects of modified-BHI medium on the growth and metabolites of Akkermansia muciniphila

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