JOURNAL OF DAIRY SCIENCE
·
2014
·
IF 2.55
Liang Li,Ying Ma
The effects of divalent metal ions (Ca 2+ , Mg 2+ , Fe 2+ , and Cu 2+ ) on the growth, β-oxidation system, and thioesterase activity of Lactococcus lactis were investigated. Different metal ions significantly influenced the growth of L. lactis : Ca 2+ and Fe 2+ accelerated growth, whereas Cu 2+ inhibited growth. Furthermore, Mg 2+ inhibited growth of L. lactis at a low concentration but stimulated growth of L. lactis at a high concentration. The divalent metal ions had significant effects on activity of the 4 key enzymes of the β-oxidation system (acyl-CoA dehydrogenase, enoyl-CoA hydratase, L-3-hydroxyacyl-CoA dehydrogenase, and thiolase) and thioesterase of L. lactis. The activity of acyl-CoA dehydrogenases increased markedly in the presence of Ca 2+ and Mg 2+ , whereas it decreased with 1 mmol/L Fe 2+ or 12 mmol/L Mg 2+ . All the metal ions could induce activity of enoyl-CoA hydratase. In addition, 12 mmol/L Mg 2+ significantly stimulated activity of L-3-hydroxyacyl-CoA dehydrogenase, and all metal ions could induce activity of thiolase, although thiolase activity decreased significantly when 0.05 mmol/L Cu 2+ was added into M17 broth. Inhibition of thioesterase activity by all 4 metal ions could be reversed by 2 mmol/L Ca 2+ . These results help us understand the effect of metal ions on the β-oxidation system and thioesterase activity of Lactococcus lactis .
研究领域:
微生物学
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生物化学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Mengna Sun,Tianyu Shi,Subiyinuer Tuerhong,Mengru Li,Qiaoli Wang,Changchang Lu,Lu Zou,Qinghua Zheng,Yingxin Wang,Juan Du,Rutian Li,Baorui Liu,Fanyan Meng
In situ vaccination is an attractive type of cancer immunotherapy, and methods of persistently dispersing immune agonists throughout the entire tumor are crucial for maximizing their therapeutic efficacy. Based on the probiotics usually used for dietary supplements, an immunomodulator-boosted Lactococcus lactis (IBL) strategy is developed to enhance the effectiveness of in situ vaccination with the immunomodulators. The intratumoral delivery of OX40 agonist and resiquimod-modified Lactococcus lactis (OR@Lac) facilitates local retention and persistent dispersion of immunomodulators, and dramatically modulates the key components of anti-tumor immune response. This novel vaccine activated dendritic cells and cytotoxic T lymphocytes in the tumor and tumor-draining lymph nodes, and ultimately significantly inhibited tumor growth and prolonged the survival rate of tumor-bearing mice. The combination of OR@Lac and ibrutinib, a myeloid-derived suppressor cell inhibitor, significantly alleviated or even completely inhibited tumor growth in tumor-bearing mice. In conclusion, IBL is a promising in situ tumor vaccine approach for clinical application and provides an inspiration for the delivery of other drugs.
研究领域:
肿瘤学
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免疫学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
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IF 10.2
Chunyi Li,Kongcheng Wang,Jie Shao,Junmeng Zhu,Yaohua Ke,Baorui Liu,Lanqi Cen
Peptide vaccines have potential for tumour immunotherapy but face challenges in clinical trials, such as human leukocyte antigen limitations, potential cytotoxic T lymphocyte tolerance, short T-cell response duration, weak immune response, and other issues. Optimizing the antigens of peptide vaccines and selecting an effective delivery system are crucial for enhancing their antitumour effects. 3 multiepitope long peptides (NLP) targeting the NY-ESO-1 antigen were screened using bioinformatics methods. An engineered Lactococcus lactis strain (FOLactis) expressing FMS-like tyrosine kinase 3 ligand and the costimulator OX40 ligand was previously developed to activate immune cells. In this study, FOLactis was utilized as a biological carrier for NLP via Mg 2+ -based metal-organic frameworks to stimulate innate and adaptive immunity. The FOL-M@NLP were characterized, and various tumour models were established to assess the antitumour efficacy of the biovaccine. The preliminary mechanism of the immune effect induced by FOL-M@NLP was studied both in vivo and in vitro . The biovaccine FOL-M@NLP was effectively taken up by antigen-presenting cells (APCs). APCs were activated, activating the T-cell response. When FOL-M@NLP was administered subcutaneously in vivo , their antitumour activity was superior to that of NLP and FOLactis alone. The biovaccine improved the immune infiltrating state of the tumour microenvironment and metastasis niche, inhibited tumor progression and prevented recurrence. It is demonstrated that FOL-M@NLP serves as a potent and safe antitumour platform that enhances antigen peptide delivery and facilitates the advancement of therapeutic biological vaccine platforms.
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Tiange Ma,Xingjiang Li,Manuel Montalbán-López,Xuefeng Wu,Zhi Zheng,Dongdong Mu
Lactococcus lactis is a crucial food-grade cell factory for secreting valuable peptides and proteins primarily via the Sec-dependent pathway. YidC, a membrane insertase, facilitates protein insertion into the lipid membrane for the translocation. However, the mechanistic details of how YidC affects protein secretion in L. lactis remain elusive. This study investigates the effects of deleting yidC1/yidC2 on L. lactis phenotypes and protein secretion. Compared to the original strain, deleting yidC2 significantly decreased the relative biomass, electroporation efficiency, and F-ATP activity by 25%, 47%, and 33%, respectively, and weakened growth and stress resistance, whereas deleting yidC1 had a minimal impact. The absence of either yidC1 or yidC2 reduced target proteins secretion. Meanwhile, there is a considerable alteration in the transcription levels of genes involved in the secretion pathway, with secY transcription increasing over 135-fold. Our results provide a theoretical foundation for further improving target protein secretion and investigating the YidC function.
研究领域:
微生物学
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生物技术
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蛋白质工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DAIRY SCIENCE
·
2013
·
IF 2.566
Liang Li,Ying Ma
The influence of fatty acids on the β-oxidation system and thioesterase of Lactococcus lactis was investigated in this study. The results showed that fatty acids (C8:0–C16:0) significantly inhibited the growth of Lactococcus lactis , and laurate (C12:0) had the highest bactericidal effects. We detected the maximum activity of β-oxidation at different incubation times (8, 12, and 18 h) to be 6.460, 7.751, and 8.203, respectively, and the maximum activity of thioesterase at different incubation times (8, 12, and 18 h) to be 19.498, 27.180, and 12.800, respectively. Fatty acids were seen to induce the β-oxidation system and activity of thioesterase; decanoic acid (C10:0) and palmitic acid (C16:0) were also seen to induce the β-oxidation system of Lactococcus lactis , but the induced ability was significantly different. Octanoic acid (C8:0) and palmitic acid (C16:0) were seen to induce thioesterase activity in Lactococcus lactis . When 1 m M palmitic acid (C16:0) was added to M17 broth, the activity of thioesterase increased 5-fold after 2 min; however, adding octanoic acid (C8:0) changed the activity little. Evidence showed that the ability to induce the β-oxidation system and thioesterase activity was related to the fatty acids’ chain lengths.
研究领域:
微生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
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2022
·
IF 6.056
Yangrui Wang,Mengtong Sun,Xiaoling Cui,Yongyue Gao,Xinran Lv,Jianrong Li,Fengling Bai,Xuepeng Li,Defu Zhang,Kai Zhou
Vibrio harveyi is one of the main pathogenic bacteria in the aquaculture industry, and quorum sensing (QS) plays key role in its pathogenicity. Previous studies have demonstrated that a metabolite with protein properties isolated from Lactococcus lactis LY3-1 showed anti-QS activity against V. harveyi . In this study, this metabolite of L. lactis LY3-1 was identified as peptide LQLY3-1, with a 1.09 kDa molecular mass, which was purified via ethyl acetate extraction followed by ultrafiltration, Sephadex G25 gel chromatography, and high-performance liquid chromatography. Its amino acid sequence was ALSLVKIHGR, as demonstrated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Crude extracts of peptide LQLY3-1 at sub-minimum inhibitory concentrations inhibited V. harveyi biofilm formation and the production of virulence factors, including exopolysaccharide, proteolytic enzymes, hemolysin, gelatinase, and motility, albeit without inhibiting bacterial growth. Scanning electron microscopy images indicated that the crude extracts of peptide LQLY3-1 disrupted the integrity of the V. harveyi biofilm. Additionally, molecular docking analysis indicated that peptide LQLY3-1 could competitively bind to the LuxN receptor protein with its natural ligand N-octanoyl- l -homoserine lactone, thereby blocking the signal transmission of the QS system. These results suggested that peptide LQLY3-1 can be used as a promising QS inhibitor to control V. harveyi pathogenicity.
研究领域:
微生物学
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海洋生物学
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水产养殖
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产品关联
DOI
高影响因子
Journal for ImmunoTherapy of Cancer
·
2025
·Vol. 13
·期 8
·e011799
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IF 10.6
Ziqi Chen,Yaohua Ke,Junmeng Zhu,Lanqi Cen,Wenmei Rao,Sen Hong,Yan Wang,Jie Shao,Yanhong Chu,Xiaoping Qian,Baorui Liu,Rutian Li,Qin Liu
Background Combining chemotherapy with immunotherapy is a promising strategy to enhance in situ immunity by increasing antigen exposure and inflammation in the tumor microenvironment (TME). However, the inconvenience of separate administration and the randomness of delivery can diminish the synergistic effect of these treatments. An efficient co-delivery system to optimize chemo-immunotherapy is urgently needed. Methods We have previously developed an engineered Lactococcus lactis (FOLactis) expressing Flt3L and OX40L to activate immune cells. Here, we biomineralized FOLactis by magnesium (Mg 2+ )-based frameworks (Mg-metal-organic frameworks (MOFs)) loaded with cisplatin and vincristine (D&V@FOLactis) to achieve sequential activation of in situ antitumor efficacy. The biomineralized D&V@FOLactis was characterized by scanning electron microscope. Confocal laser scanning microscopy, flow cytometry analysis, and immunofluorescence were employed to assess the biodistribution and the synergistic antitumor mechanisms of D&V@FOLactis in TME. Results On intratumoral administration, D&V@FOLactis exhibited pH-responsive drug release, primarily inducing immunogenic cell death and enhancing antigen exposure. Subsequently, FOLactis acted as immunopotentiators to recruit immune cells and maintain long-lasting effect. D&V@FOLactis was instrumental in thoroughly improving TME, activating T-cell responses, suppressing both “cold” and “hot” tumors with abscopal effect, and prolonging survival. In the clinical trial involving three patients, the combination of D&V@FOLactis with radiotherapy suggested potential improvements in systemic immunity and a possible reduction in multiple types of tumors. Conclusions We achieved the sequential activation of synergistic chemo-immunotherapy using an all-in-one biomineralized strategy. This study marked the first instance of biomineralizing probiotics with Mg-MOFs, creating a biosafe and versatile platform for combined in situ vaccination treatment.
研究领域:
癌症免疫治疗
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生物工程
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纳米医学
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微生物学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 19
·3054
·
IF 4.7
Jiacui Shang,Lijun Liu,Shuo Yang,Bofan Duan,Shuiqi Xie,Xiangchen Meng
Chronic inflammation is a factor in the development of cancer, and probiotics play a role in preventing or treating inflammation as an adjuvant therapy. To investigate potential probiotics for the prevention of colitis-associated colorectal cancer (CAC), Bifidobacterium bifidum H3-R2 and Lactococcus lactis KLDS4.0325 were used to examine the effects on colon cancer cells and in an inflammation-related cancer animal model. The results revealed that B. bifidum H3-R2 in combination with L. lactis KLDS4.0325 caused apoptosis in colon cancer cells by increasing caspase-3 and caspase-9 protein levels, enhancing Bax expression, and lowering Bcl-2 expression. In addition, the combination of the two strains relieved the tissue damage; reduced proinflammatory cytokines, myeloperoxidase (MPO) activity, and hypoxia-inducible factor 1-alpha (HIF-1α) level; upregulated anti-inflammatory cytokines; increased colonic tight junction protein expression; regulated intestinal homeostasis by inhibiting NLRP3 inflammasome signaling pathway; and improved the imbalance of gut microbiota in animal models. Moreover, the combination of the two strains had a greater preventive impact than each strain alone. These findings are supportive of clinical studies and product development of multi-strain probiotic preparations for diseases associated with colitis.
研究领域:
微生物学
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癌症研究
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胃肠病学
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DOI
PubMed
高影响因子
CyTA-Journal of Food
·
2018
·
IF 1.371
Liang Li,Ying Ma
Methyl ketones can be formed by the metabolism of intermediate products of β-oxidation by enzymes. In this article, the effect of soluble saccharides on the activity of key enzymes involved in methyl ketone synthesis in L. lactis was studied by detecting the relationship between soluble saccharides and enzyme activity. The results showed that glucose, fructose, sucrose, lactose and galactose could promote the growth of L. lactis. Glucose induced the activity of enoyl-coenzyme A (CoA) hydratase but inhibited the activity of β-hydroxyacyl-CoA dehydrogenase. Fructose induced the activities of acyl-CoA dehydrogenase and enoyl-CoA hydratase while maintaining the activity of β-hydroxyacyl-CoA dehydrogenase. Sucrose induced the activities of enoyl-CoA hydratase and β-hydroxyacyl-CoA dehydrogenase and maintained the activity of thiolase. Lactose also induced enoyl-CoA hydratase activity. Galactose induced enoyl-CoA hydratase activity and maintained thiolase activity. Glucose, lactose, fructose and galactose induced thioesterase activity. The data showed fructose and lactose could inhibit thiolase activity and induce thioesterase activity, which would be beneficial to methyl ketone synthesis, so fructose and lactose were the best soluble saccharides, followed by galactose, glucose and sucrose. A positive and significant correlation was found between thioesterase activity and enoyl-CoA hydratase activity (p < 0.01). In summary, the β-oxidation system of L. lactis is related to sugar metabolism.
研究领域:
微生物学
·
生物化学
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DOI
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Yang Yang,Zhao Yuanji,Lei Huan
Introduction: This study aimed to explore the anti-oxidative and anti-inflammatory properties of Lactococcus lactis subsp. lactis HFY14 (LLSLHFY14) and investigate its effects on the intestinal barrier, cranial nerve, and motor function in mice treated with antibiotics.Methods: Mice were administered an antibiotic mixture (neomycin 5 mg/mL, vancomycin 25 mg/mL, amphotericin B 0.1 mg/mL, ampicillin 10 mg/mL, metronidazole file 5 mg/mL, and lipopolysaccharide 1.5 μg/mL) intraperitoneally, and oxidative stress and inflammatory markers in the serum and brain tissues, and liver index were measured. H&E staining was performed to detect pathological alterations in brain tissues. The expression of intestinal-barrier-related genes and that of genes involved in inflammatory pathways in the brain were detected using polymerase chain reaction (PCR).Results: LLSLHFY14 administration extended the weight-loaded swimming and running times of mice and decreased the liver index. Moreover, the levels of malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the serum and brain tissue were reduced, whereas those of superoxide dismutase (SOD), glutathione (GSH), and interleukin-10 (IL-10) were elevated. Elevated brain expression of the protein kinase B (AKT)/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/extracellular signal-regulated kinase 1 (ERK1) pathway, decreased brain expression of the IL-6 gene, and elevated cecum expression of zonula occludens-1 (ZO-1), occludin-1, and claudin-1 genes were noted. LLSLHFY14 supplementation significantly increased Bacteroidetes expression but decreased Firmicutes expression, thus increasing the Bacteroidetes/Firmicutes ratio.Discussion: Overall, LLSLHFY14 supplementation ameliorated antibiotic-induced oxidative stress and inflammation in the mouse central nervous system, intestinal barrier dysfunction, and increased motor function, thus confirming its potential application as probiotics.
研究领域:
微生物学
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神经科学
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免疫学
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药理学
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益生菌
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Jia-Jun Liao,Mei-ling Zhou,Deng-Yi Lin,Zsolt Zalán,Hua-Yi Suo
Hyperuricemia and gout have evolved into a global health burden, necessitating the development of innovative approaches for their long-term dietary management. In this study, food-grade Lactococcus lactis was genetically engineered by introducing urate oxidase (UOX) genes from GRAS strains, to construct novel engineered lactic acid bacteria (LAB) with biosafety and UA-lowering performance. The results showed that the engineered LAB possessed excellent uric acid (UA) degradation ability. The specific UOX activities of L. lactis NZ3900/pNZ8149- pucL and L. lactis NZ3900/pNZ8149- CuUOX were (21.38 ± 0.17) U/mg and (28.06 ± 0.44) U/mg, respectively. High-performance liquid chromatography (HPLC) detection revealed that their degradation rates against 1 mmol/L UA reached 82.16% ± 4.39% and 35.48% ± 1.13% at 3 h. An in vitro Transwell model further validated their capacity for UA absorption and transport. Hemolytic activity and antibiotic susceptibility assessments indicated the favorable biosafety of the engineered LAB. This novel UA-lowering engineered LAB offers a promising candidate for developing functional foods and probiotic dietary preparations to prevent and alleviate hyperuricemia and gout.
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DOI
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2024
·
IF 6
Yulong Zhang,Suo Zheng,Jingru Chen,Zhiliang Cheng,Fei Liu,Yuehua Jiao
Lactococcus lactis undergoing aerobic respiration can consume oxygen and form an anaerobic environment. Salmonella , as a facultative anaerobic foodborne pathogen, multiply better under aerobic conditions. The purpose of this study was to explore aerobic respiration of Lactococcus lactis subsp. lactis ( L. lactis ) KLDS 4.0325 inhibitory effect on Salmonella enterica subsp. enterica serovar Typhimurium ( S. Typhimurium) SL 1344 in vitro and its colonization ability in vivo . Results indicate that L. lactis KLDS 4.0325 could inhibit the growth of S. Typhimurium SL1344 by producing bacteriocin. And L. lactis KLDS 4.0325 undergoing aerobic respiration could enhance this inhibitory effect, while reducing the expression levels of virulence genes sipB , sipC , and sopE2 in S. Typhimurium SL1344. L. lactis KLDS 4.0325 could be successfully labeled by CFDA-SE fluorescent probe, and the labeling rate was more than 97%. Murine experiments showed that L. lactis KLDS 4.0325 could adhere and colonize in the cecum and colon. Thus, L. lactis KLDS 4.0325 is a promising probiotic strain for the potential inhibition of Salmonella infection via its oxygen-scavenging in host gut.
研究领域:
微生物学
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食品安全
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分子生物学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）