Amuc_1102 from Akkermansia muciniphila adopts an immunoglobulin-like fold related to archaeal type IV pilus

Xiang, Rui; Wang, Junchao; Xu, Wenjuan; Zhang, Min; Wang, Mingzhu

doi:10.1016/j.bbrc.2021.02.022

Cited by 5 publications

(5 citation statements)

References 38 publications

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“…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. Given this context, we chose Amuc1102 as our protein of interest.…”

Section: Resultsmentioning

confidence: 99%

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%

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 proteins encoded by the Amuc_1098 gene cluster, which play a role in pilus formation and assembly, exhibit high levels of expression in the membrane protein components of Akkermansia muciniphila 20 . Akkermansia muciniphila could modulate lipid and immune homeostasis, improve gut microbiota, and promote the overall health 38 .…”

Section: Discussionmentioning

confidence: 99%

“…There was a decrease of butyrate-producing bacteria and an increased Akkermansia muciniphila following pancreatitis 19 . The protein encoded by Amuc_1098 gene cluster is highly expressed in the membrane protein components of Akkermansia muciniphila, which is related to the formation of fimbriae 20 . Intestinal permeability and gut microbiota play an important role in AP.…”

Section: Introductionmentioning

confidence: 99%

A purified membrane protein Amuc_1098 from Akkermansia muciniphila blunts acute pancreatitis by modulation of intestinal flora and glycerophospholipid metabolism

Wang,

Zhang,

Zhao

et al. 2024

Preprint

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Amuc_1098 is a membrane protein from Akkermansia muciniphila. In this study, we investigated how Amuc_1098 affects acute pancreatitis (AP) in mice induced by caerulein and lipopolysaccharide (LPS). Treating mice with Amuc_1098 (3 μg, i.g.) for 20 days before caerulein and LPS injection reduced pancreatic injury and lowered serum amylase and lipase levels. Amuc_1098 supplementation reduced proinflammatory cytokines (TNF-α, IL-1β and IL-6) in spleen and pancreas by inhibiting NF-κB signaling. It also decreased Ly6C+ macrophages in the spleen and pancreas of AP mice. Amuc_1098 pretreatment reversed declined tight junction proteins in the colon of AP mice. Glycerophospholipid metabolism was significantly increased in patients and mice with AP. We further demonstrated that oral administration of Amuc_1098 reduced glycerophospholipid metabolism enrichment mediated by intestinal flora. These results provide new evidence that Amuc_1098 lessens the severity of AP through its anti-inflammatory properties with a reduction of macrophage infiltration in spleen and pancreas, an elevation of tight junction proteins in the colon, as well as its regulation of the composition of intestinal flora and glycerophospholipid metabolism.

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“…Its unique structure enables A. muciniphila to modulate gut barrier integrity, enhance gut permeability, and thicken the mucus layer in HFD mice ( Chelakkot et al., 2018 ; Liu et al., 2019 ). Furthermore, the Type IV pili of A. muciniphila are able to directly signal to host immune receptors, regulate the expression of genes involved in fat synthesis and inflammation in the liver, and maintain gut immune system homeostasis ( Zhou and Zhang, 2019 ; Kim et al., 2020 ; Yang et al., 2020 ; Xiang et al., 2021 ) . A. muciniphila is also capable of secreting oligosaccharides and SCFA, which act as growth substrates for other beneficial bacteria and promote the abundance of microbiota associated with a reduced risk of obesity ( Belzer and de Vos, 2012 ; Clarke et al., 2014 ; Keshavarz Azizi Raftar et al., 2021 ).…”

Section: Probiotics Are Promising To Be a New Strategy For Treating H...mentioning

confidence: 99%

Research progress of gut microbiota and obesity caused by high-fat diet

Fan

Chen²,

Lin

2023

Front. Cell. Infect. Microbiol.

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Obesity, a chronic metabolic disorder caused by an energy imbalance, has been increasingly prevalent and poses a global health concern. The multifactorial etiology of obesity includes genetics factors, high-fat diet, gut microbiota, and other factors. Among these factors, the implication of gut microbiota in the pathogenesis of obesity has been prominently acknowledged. This study endeavors to investigate the potential contribution of gut microbiota to the development of high-fat diet induced obesity, as well as the current state of probiotic intervention therapy research, in order to provide novel insights for the prevention and management of obesity.

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Amuc_1102 from Akkermansia muciniphila adopts an immunoglobulin-like fold related to archaeal type IV pilus

Cited by 5 publications

References 38 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

A purified membrane protein Amuc_1098 from Akkermansia muciniphila blunts acute pancreatitis by modulation of intestinal flora and glycerophospholipid metabolism

Research progress of gut microbiota and obesity caused by high-fat diet

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