Teichoic acid(TA)derived from different Gram-positive bacteria exhibit distinct effects on host inflammatory responses.In this study,we investigated the inflammation modulation of TAs from Lactiplantibacillus plantaru...Teichoic acid(TA)derived from different Gram-positive bacteria exhibit distinct effects on host inflammatory responses.In this study,we investigated the inflammation modulation of TAs from Lactiplantibacillus plantarum(L.plantarum)AR113 by AR113 key TA-synthesizing gene knockout strains.Our findings show that the presence of TAs attenuated the anti-inflammatory activity of AR113 by diminished pro-inflammatory signaling pathway triggered by TLR2(MyD88/MAPK axis)in macrophages.And ultimately manifested in vitro with AR113Δltas stimulated cells to produce nitric oxide(NO)at 15.8%lower,AR113Δdlt at 48.5%lower,and AR113ΔtagO at 51.2%lower levels compared to AR113(p<0.05).In addition,whether in vitro or in vivo,AR113ΔtagO effectively could reduce pro-inflammatory cytokine production,while AR113Δltas and AR113Δdlt could promoted the production of anti-inflammatory cytokine than AR113.Notably,D-Ala branch chain appears to be a key factor in the inflammatory response to TAs produced by AR113,since only the cytotoxic effect of AR113Δdlt on macrophages was significantly reduced compare to AR113(p<0.01);and that AR113Δdlt demonstrated the most effective relief of colitis symptoms,reducing the disease activity index(DAI)better than the AR113 intervention group(4.45±1.73 vs 5.30±1.85).However,further studies on the intestinal barrier in mice shown that TAs produced by AR113 had no significant effect on barrier-related genes,indicates that the TAs does not cause damage to the intestinal barrier of mice,they primarily target immune responses.Overall,this study identifies potential targets for enhancing the anti-inflammatory properties of probiotics.展开更多
Among the 14 serovars of Listeria monocytogenes(Lm),serovar 4b strains are the most predominant isolates linked to human listeriosis outbreaks-a phenotype associated with their unique wall teichoic acid(WTA)decorated ...Among the 14 serovars of Listeria monocytogenes(Lm),serovar 4b strains are the most predominant isolates linked to human listeriosis outbreaks-a phenotype associated with their unique wall teichoic acid(WTA)decorated with galactose(Gal)and glucose(Glu).A wealth of knowledge is available for galactosylated-WTA(Gal-WTA)manipulating bacterial homeostasis and virulence,whereas the relationship between glucosylated-WTA(Glu-WTA)and Gal-WTA in listerial physiology and pathogenesis remains unclear.Here,we find that Glu-WTA and Gal-WTA jointly constitute the O-antigen pattern of serovar 4b Lm;however,Glu-WTA specifically serves as the indispensable ligand for listeriophage LP4 adsorption.Moreover,the co-operation between Glu-and Gal-WTA increases biofilm formation and bacterial resistance to cationic antimicrobial peptide(CRAMP).We further demonstrate that Gal-WTA modulates the anchoring of surface proteins,including IspC,Ami,and InlB.Additionally,dual glycosylated WTA interaction with ActA facilitates bacterial intracellular motility and dissemination.Consistently,Glu-WTA significantly enhances bacterial colonization ability in the mesenteric lymph nodes(MLNs),ileum,liver,and brain of mouse,cooperating with Gal-WTA to facilitate Lm dissemination to distant organs and tissues.In conclusion,we reveal the crucial roles of Glu-WTA in synergizing with Gal-WTA to modulate the integrity of the cell wall structure and exacerbate bacterial infection,providing a global understanding of the hypervirulence and pathogenicity of invasive serovar 4b Lm.展开更多
1 Results Several methods have been elaborated in this laboratory allowing preparation of macromolecules with phosphodiester bonds,and having sequence of atoms similar as in the chains of biomacromolecules - nucleic o...1 Results Several methods have been elaborated in this laboratory allowing preparation of macromolecules with phosphodiester bonds,and having sequence of atoms similar as in the chains of biomacromolecules - nucleic or teichoic acids (TA),namely:-(C)n-O-PO-,where n=2 (for teichoic acids) or 3.These methods,to be discussed in the lecture,are based on the ring-opening polymerization,transesterification,and recently elaborated direct addition of phosphoric acid to diepoxides.For the first time an attempt h...展开更多
Staphylococcus aureus is a major public health threat,largely due to its remarkable capacity to develop antimicro-bial resistance.Zhang et al.recently demonstrated a highly innovative approach to eradicate chronic met...Staphylococcus aureus is a major public health threat,largely due to its remarkable capacity to develop antimicro-bial resistance.Zhang et al.recently demonstrated a highly innovative approach to eradicate chronic methicillin-resistant S.aureus infections by inducing bacterial calcification with antibody-polysialic acid conjugates targeting wall teichoic acids,while simultaneously modulating host immune responses via enhanced calprotectin expres-sion and macrophage activation.Despite limitations,this strategy represents a promising and unconventional therapy to combat resistant S.aureus infections.展开更多
基金supported by National Natural Science Foundation,China(No.32472304)National Science Fund for Distinguished Young Scholars,China(No.32025029)+2 种基金the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission,Wuxi Industrial Innovation Research Institute Pilot Technology Pre-research Project(No.XD23001)Shanghai Education Committee Scientific Research Innovation Projects(No.2101070007800120)Shanghai Engineering Research Center of Food Microbiology Program(No.19DZ2281100).
文摘Teichoic acid(TA)derived from different Gram-positive bacteria exhibit distinct effects on host inflammatory responses.In this study,we investigated the inflammation modulation of TAs from Lactiplantibacillus plantarum(L.plantarum)AR113 by AR113 key TA-synthesizing gene knockout strains.Our findings show that the presence of TAs attenuated the anti-inflammatory activity of AR113 by diminished pro-inflammatory signaling pathway triggered by TLR2(MyD88/MAPK axis)in macrophages.And ultimately manifested in vitro with AR113Δltas stimulated cells to produce nitric oxide(NO)at 15.8%lower,AR113Δdlt at 48.5%lower,and AR113ΔtagO at 51.2%lower levels compared to AR113(p<0.05).In addition,whether in vitro or in vivo,AR113ΔtagO effectively could reduce pro-inflammatory cytokine production,while AR113Δltas and AR113Δdlt could promoted the production of anti-inflammatory cytokine than AR113.Notably,D-Ala branch chain appears to be a key factor in the inflammatory response to TAs produced by AR113,since only the cytotoxic effect of AR113Δdlt on macrophages was significantly reduced compare to AR113(p<0.01);and that AR113Δdlt demonstrated the most effective relief of colitis symptoms,reducing the disease activity index(DAI)better than the AR113 intervention group(4.45±1.73 vs 5.30±1.85).However,further studies on the intestinal barrier in mice shown that TAs produced by AR113 had no significant effect on barrier-related genes,indicates that the TAs does not cause damage to the intestinal barrier of mice,they primarily target immune responses.Overall,this study identifies potential targets for enhancing the anti-inflammatory properties of probiotics.
基金supported by the National Natural Science Foundation of China(32161133025 and 32373012)the Key Research and Development Program of Jiangsu(BE2021331)+2 种基金111 Project(D18007)the Priority Academic Development Program of Jiangsu Higher Education Institutions(PAPD),the State-funded Postdoctoral Researchers Program(GZC20241437)the Jiangsu Funding Program for Excellent Postdoctoral Talent(2024ZB641).
文摘Among the 14 serovars of Listeria monocytogenes(Lm),serovar 4b strains are the most predominant isolates linked to human listeriosis outbreaks-a phenotype associated with their unique wall teichoic acid(WTA)decorated with galactose(Gal)and glucose(Glu).A wealth of knowledge is available for galactosylated-WTA(Gal-WTA)manipulating bacterial homeostasis and virulence,whereas the relationship between glucosylated-WTA(Glu-WTA)and Gal-WTA in listerial physiology and pathogenesis remains unclear.Here,we find that Glu-WTA and Gal-WTA jointly constitute the O-antigen pattern of serovar 4b Lm;however,Glu-WTA specifically serves as the indispensable ligand for listeriophage LP4 adsorption.Moreover,the co-operation between Glu-and Gal-WTA increases biofilm formation and bacterial resistance to cationic antimicrobial peptide(CRAMP).We further demonstrate that Gal-WTA modulates the anchoring of surface proteins,including IspC,Ami,and InlB.Additionally,dual glycosylated WTA interaction with ActA facilitates bacterial intracellular motility and dissemination.Consistently,Glu-WTA significantly enhances bacterial colonization ability in the mesenteric lymph nodes(MLNs),ileum,liver,and brain of mouse,cooperating with Gal-WTA to facilitate Lm dissemination to distant organs and tissues.In conclusion,we reveal the crucial roles of Glu-WTA in synergizing with Gal-WTA to modulate the integrity of the cell wall structure and exacerbate bacterial infection,providing a global understanding of the hypervirulence and pathogenicity of invasive serovar 4b Lm.
文摘1 Results Several methods have been elaborated in this laboratory allowing preparation of macromolecules with phosphodiester bonds,and having sequence of atoms similar as in the chains of biomacromolecules - nucleic or teichoic acids (TA),namely:-(C)n-O-PO-,where n=2 (for teichoic acids) or 3.These methods,to be discussed in the lecture,are based on the ring-opening polymerization,transesterification,and recently elaborated direct addition of phosphoric acid to diepoxides.For the first time an attempt h...
基金financially supported by Independent Research Fund,Denmark(2035-00110B)the Novo Nordisk Foundation,Denmark(NNF22OC0077593)awarded to Hanne Ingmer.
文摘Staphylococcus aureus is a major public health threat,largely due to its remarkable capacity to develop antimicro-bial resistance.Zhang et al.recently demonstrated a highly innovative approach to eradicate chronic methicillin-resistant S.aureus infections by inducing bacterial calcification with antibody-polysialic acid conjugates targeting wall teichoic acids,while simultaneously modulating host immune responses via enhanced calprotectin expres-sion and macrophage activation.Despite limitations,this strategy represents a promising and unconventional therapy to combat resistant S.aureus infections.
