Natural Product Communications
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2021
·
IF 0.986
Zheng Liu,Lihua Zhang,Jincai Wang,Yanping Li,Yiqun Chang,Xiaoling Huang,Jun Duan,Yilong Ai,Xuxin Zeng,Jialiang Guo
Biofilm formation is considered as a crucial factor in various oral diseases, such as dental caries. The quorum sensing (QS) signaling system was proved to have a crucial role in the microbial dental plaque biofilm formation of Streptococcus mutans (S. mutans). LuxS was critical to regulating the QS system and survival of the bacterium, and, therefore, compounds which target LuxS may be a potential therapy for dental caries. The binding activities of 37,170 natural compounds to LuxS were virtually screened in this study. Baicalein and paeonol were chosen for further research of the binding mode and ΔG values with LuxS. Both baicalein and paeonol inhibited the biofilm formation without influence on the growth of S. mutans. Baicalein also distinctly reduced the production of both rhamnolipids and acids. The results provide us with a new approach to combat dental caries instead of the traditional use of antibacterial chemicals.
研究领域:
微生物学
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药物化学
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口腔医学
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DOI
高影响因子
Journal of Functional Foods
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2025
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IF 4
Zhaoxi Deng,Yanfei Ma,Kangwei Hou,Jinyan Dai,Yifan Zhong,Yingying Mao,Jinzhi Zhang,Haifeng Wang
Quorum sensing (QS) is an essential pathway for bacterial communication through autoinducers (AIs). The luxS gene involved in QS has been proven to regulate different behavior of Lactobacillus rhamnosus GG (LGG), whereas it is unclear whether the AI-2/LuxS system have beneficial effects the host by regulating LGG. Our aim was to investigate whether luxS mutation affects the ability of LGG to maintain intestinal microbiota homeostasis, intestinal barrier integrity and inflammatory immune responses in mice infected with Escherichia coli ( E. coli ). This study showed that both wild-type (WT) and luxS mutant (ΔluxS) of LGG can alleviate changes in the microbiota caused by E. coli by down-regulating the relative abundance of Parasturtella . Supplementation with WT and ΔluxS increased the CD4 + /CD8 + ratio in spleen, improved goblet cell numbers and enhanced Muc 2 secretion. Moreover, WT and ΔluxS decreases proinflammatory mediator levels by inhibiting MAPK and NF-κB signal transduction.
研究领域:
微生物学
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免疫学
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分子生物学
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产品关联
DOI
高影响因子
Biomolecules
·
2024
·Vol. 14
·期 4
·452
·
IF 4.8
Bingbing Zong,Yong Xiao,Peiyi Wang,Wei Liu,Mingxing Ren,Changyan Li,Shulin Fu,Yanyan Zhang,Yinsheng Qiu
Porcine extraintestinal pathogenicEscherichia coli(ExPEC) is a pathogenic bacterium that causes huge economic losses to the pig farming industry and considerably threatens human health. The quorum sensing (QS) system plays a crucial role in the survival and pathogenesis of pathogenic bacteria. Hence, it is a viable approach to prevent ExPEC infection by compromising the QS system, particularly the LuxS/AI-2 system. In this study, we investigated the effects of baicalin on the LuxS/AI-2 system of ExPEC. Baicalin at concentrations of 25, 50, and 100 μg/mL significantly diminished the survival ability of ExPEC in hostile environments and could inhibit the biofilm formation and autoagglutination ability in ExPEC. Moreover, baicalin dose-dependently decreased the production of AI-2 and down-regulated the expression level ofluxSin PCN033. These results suggest that baicalin can weaken the virulence of PCN033 by inhibiting the LuxS/AI-2 system. After the geneluxSwas deleted, AI-2 production in PCN033 was almost completely eliminated, similar to the effect of baicalin on the production of AI-2 in PCN033. This indicates that baicalin reduced the production of AI-2 by inhibiting the expression level ofluxSin ExPEC. In addition, the animal experiment further showed the potential of baicalin as a LuxS/AI-2 system inhibitor to prevent ExPEC infection. This study highlights the potential of baicalin as a natural quorum-sensing inhibitor for therapeutic applications in preventing ExPEC infection by targeting the LuxS/AI-2 system.
研究领域:
微生物学
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药理学
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兽医学
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产品关联
DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
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2023
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IF 3.8
Jing Zuo,Yamin Shen,Haikun Wang,Shuji Gao,Shuo Yuan,Dong Song,Yuxin Wang,Yang Wang
Streptococcus suis ( S. suis ) regulates biofilm formation through LuxS/AI-2 quorum sensing system, increasing drug resistance and exacerbating infection. The anti-hyperglycaemic agent metformin has anti-bacterial and anti-biofilm activities. This study aimed to investigate the anti-biofilm and anti-quorum sensing activity of metformin in S. suis . We first determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of metformin on S. suis . The results indicated that metformin showed no obvious inhibitory or bactericidal effect . Crystal violet staining showed that metformin significantly inhibited the formation of S. suis biofilm at sub-MIC concentration, which was also confirmed by scanning electron microscopy. Then, we quantified the AI-2 signal molecules in S. suis , and the results showed that metformin had a significant inhibitory effect on the production of AI-2 signal in S. suis . Inhibition of enzyme activity and molecular docking experiments showed that metformin has a significant binding activity to LuxS protein. In addition, qRT-PCR results showed that metformin significantly down-regulated the expression of AI-2 synthesis-related genes luxS and pfs , and adhesion-related genes luxS , pfs , gapdh , sly , fbps, and ef . Western blotting also showed that metformin significantly reduced the expression of LuxS protein. Our study suggests that metformin seems to be a suitable candidate for the inhibition of S. suis LuxS/AI-2 QS system and prevention of biofilm formation, which provided a new idea for the prevention and control of S. suis .
研究领域:
微生物学
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药理学
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传染病学
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产品关联
DOI
PubMed
高影响因子
Journal of Integrative Agriculture
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2024
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IF 4.6
Jing Zuo,Yingying Quan,Yue Li,Dong Song,Jinpeng Li,Yuxin Wang,Li Yi,Yang Wang
Streptococcus suis is a significant zoonotic agent affecting both human and pig health and poses a substantial public health concern. The pathogenicity of S. suis is intricately linked to its ability to form biofilms and express virulence factors, which are regulated by the LuxS/AI-2 quorum sensing (QS) system. Herein, we uncover a novel therapeutic avenue by demonstrating that 5-fluorouracil (5-FU), an FDA-approved anti-cancer agent, effectively mitigates biofilm formation and attenuates the virulence of S. suis . Mechanistically, we observe a significant reduction in capsular polysaccharide and extracellular polysaccharide production upon 5-FU treatment, elucidating a potential mechanism for biofilm weakening. Additionally, 5-FU down-regulates virulence traits, diminishing S. suis ‘s ability to adhere to host cells and evade phagocytosis. Crucially, our study identifies the thymidylate synthase regulatory gene thyA as a key mediator of 5-FU’s effects on the LuxS/AI-2 QS system. Virtual molecular docking and gene knockout experiments provide compelling evidence that 5-FU modulates the LuxS/AI-2 QS system by targeting thyA . In vivo experiments further validate the therapeutic potential of 5-FU, showcasing a significant reduction in bacterial load and mitigation of tissue damage in a mouse model. In conclusion, our investigation unveils 5-FU as a potent disruptor of S. suis ‘s biofilm formation and virulence, offering a promising avenue for the control of this devastating pathogen.
研究领域:
微生物学
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感染病学
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药理学
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产品关联
DOI
高影响因子
Microbiology Spectrum
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2022
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IF 9.043
Zhaoxi Deng,Kangwei Hou,Teresa G. Valencak,Xin M. Luo,Jianxin Liu,Haifeng Wang
The LuxS enzyme plays a key role in both quorum sensing (QS) and the regulation of bacterial growth. It catalyzes the production of autoinducer-2 (AI-2) signaling molecule, which is a component of the methyl cycle and methionine metabolism. This study aimed at investigating the differences between the Lactobacillus rhamnosus GG (LGG) wild-type strain (WT) and its luxS mutant (ΔluxS) during biofilm formation and when resisting to inflammation caused by Enterotoxigenic Escherichia coli (ETEC) in germ-free zebrafish. Our results suggest that in the absence of luxS when LGG was knocked out, biofilm formation, extracellular polysaccharide secretion and adhesion were all compromised. Addition of synthetic AI-2 indeed rescued, at least partially, the deficiencies observed in the mutant strain. The colonizing and immunomodulatory function in WT versus ΔluxS mutants were further studied in a germ-free zebrafish model. The concentration of AI-2 signaling molecules decreased sharply in zebrafish infected with the ΔluxS. At the same time, compared with the ΔluxS, the wild-type strain could colonize the germ-free zebrafish more effectively. Our transcriptome results suggest that genes involved in immunity, signal transduction, and cell adhesion were downregulated in zebrafish infected with ΔluxS and WT. In the WT, the immune system of germ-free zebrafish was activated more effectively through the MAPK and NF-κB pathway, and its ability to fight the infection against ETEC was increased. Together, our results demonstrate that the AI-2/LuxS system plays an important role in biofilm formation to improve LGG and alleviate inflammation caused by ETEC in germ-free zebrafish.IMPORTANCE Lactobacillus rhamnosus GG is a widely used probiotic to improve host intestinal health, promote growth, reduce diarrhea, and modulate immunity. In recent years, the bacterial quorum sensing system has attracted much attention; however, there has not been much research on the effect of the LuxS/AI-2 quorum sensing system of Lactobacillus on bacteriostasis, microbial ecology balance, and immune regulation in intestine. In this study, we used germ-free zebrafish as an animal model to compare the differences between wild-type and luxS mutant strains. We showed how AI-2/LuxS QS affects the release of AI-2 and how QS regulates the colonization, EPS synthesis and biofilm formation of LGG. This study provides an idea for the targeted regulation of animal intestinal health with probiotics by controlling bacteria quorum sensing system.
研究领域:
微生物学
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免疫学
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分子生物学
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动物模型研究
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产品关联
DOI
PubMed
高影响因子
Foods
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2022
·Vol. 11
·期 9
·1203
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IF 5.561
Jiao Shi,Shu-Fang Li,Kun Feng,Shuang-Yan Han,Teng-Gen Hu,Hong Wu
For improving probiotics’ survivability under harsh conditions, this study usedLactiplantibacillus plantarumGIM1.648 as a model microorganism to investigate its ability to produce biofilms on electrospun ethyl cellulose nanofiber mats. SEM observations confirmed that biofilm was successfully formed on the nanofibers, with the latter being an excellent scaffold material. The optimal cultivation conditions for biofilm formation were MRS medium without Tween 80, a culture time of 36 h, a temperature of 30 °C, a pH of 6.5, and an inoculum concentration of 1% (v/v). The sessile cells in the biofilm exhibited improved gastrointestinal and thermal tolerance compared to the planktonic cells. Additionally, the RT-qPCR assay indicated that theluxSgene played a crucial role in biofilm formation, with its relative expression level being 8.7-fold higher compared to the planktonic cells. In conclusion, biofilm formation on electrospun nanofiber mat has great potential for improving the viability of probiotic cells under harsh conditions.Keywords:electrospun nanofiber mat;biofilm;probiotics;viability;luxSgene
研究领域:
微生物学
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食品科学
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材料科学
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DOI
PubMed
高影响因子
BIORESOURCE TECHNOLOGY
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2025
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IF 9
Yuan Li,Danchen Zhu,Linmeng Hong,Jixiang Dai,Lijun Wu
This study systematically investigated the effect of interfering with autoinducer-2 (AI-2) signaling system on controlling initial fouling attachment and irreversible components. Exposure of bacteria to the inhibitor significantly reduced the expression of the luxS gene, which resulted in a 37.3% reduction of AI-2 signaling molecule synthesis. Expression of flagellin and kinesin, which determine bacteria adhesion properties, and virulence genes was significantly down-regulated. AI-2 quorum quenching (QQ) significantly suppressed the initial biofilm growth and inhibition efficiency was positively correlated with bacteria concentration. Extracellular polymeric substances accumulation decreased by 40.8% in QQ experiment relative to the control, thus mitigating the flux decline. Polysaccharides, which constitute irreversible components, were significantly reduced by 69.3% with presence of inhibitor. AI-2 QQ altered protein and peptide structure of fouling layer, which converted irreversible fouling into reversible fouling. These findings contributed to the understanding of QQ susceptibility to initial fouling, providing a theoretical basis for engineering applications.
研究领域:
微生物学
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环境工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2026
·
IF 4.4
Jialong Huang,Guohao Chen,Tingyu Wei,Xuemin Wei,Yinghui Wang,Aiguo Huang
Streptococcus agalactiae (Group B Streptococcus, GBS) is one of the most harmful pathogens in aquaculture and its virulence is mainly regulated by the LuxS/AI-2 quorum sensing (QS) system. Developing quorum sensing inhibitors (QSIs) targeting the GBS LuxS protein is not prone to inducing drug resistance, which is of great significance for addressing the antimicrobial resistance crisis in aquaculture. This study identified naringin, a potential LuxS inhibitor with anti-GBS virulence activity, from plant-derived natural products through virtual screening combined with experimental verification. The results showed that naringin bound tightly to the entrance of the GBS LuxS active pocket and effectively inhibited luxS gene transcription. This dual action may reduce AI-2 signal molecule synthesis through both potential steric hindrance at the active site and transcriptional inhibition. At sub-inhibitory concentrations, naringin did not inhibit bacterial growth. Instead, it downregulated key virulence genes, significantly suppressed EPS secretion, and disrupted the biofilm barrier, thereby attenuating bacterial virulence. The results of in vivo challenge experiments showed that naringin intervention significantly alleviated histopathological damage in infected hosts and effectively improved the survival rate after infection. This protective effect may be closely associated with the ability of naringin to inhibit the colonization and dissemination of GBS in the host spleen and brain tissues, while downregulating host pro-inflammatory gene expression and upregulating antioxidant gene expression. This study confirmed that naringin can effectively disrupt the GBS LuxS/AI-2 quorum sensing system and exert significant anti-virulence effects. It also provides a new candidate drug and theoretical basis for the green prevention and control of GBS infection in aquaculture.
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产品关联
DOI
高影响因子
Food Bioscience
·
2024
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IF 4.8
Yumeng Sui,Jiasheng Lu,Ying-ao Zhu,Baohua Kong,Hui Wang,Ligang Qin,Qian Chen
The effects of the exogenous autoinducer-2 (AI-2) precursor, 4,5-dihydroxy-2,3-pentanedione (DPD; 0, 300, 600, and 900 nmol/L), on the degradation capacity of Lactiplantibacillus plantarum SH7 toward biogenic amines (BA) were investigated both in vitro and in a dry-sausage model. L. plantarum SH7 exhibited a significant increase in BA-degradation capacity (putrescine, cadaverine, and histamine) under DPD treatments compared to the absence of DPD treatment in vitro . Additionally, a significant increase in the production of AI-2 signal molecule and diamine oxidase in L. plantarum SH7 was observed with the addition of exogenous DPD ( p < 0.05). In the dry-sausage model, the contents of BAs (tryptamine, 2-phenethylamine, putrescine, cadaverine, and histamine) significantly decreased with the addition of DPD ( p < 0.05). Meanwhile, the sausage with 600-nM DPD exhibited the lowest cadaverine content (11.13 mg/kg), while the sausage with 900-nM DPD exhibited the lowest tryptamine, putrescine, and histamine contents (12.44, 11.15, and 13.21 mg/kg, respectively). Results suggest that an optimal concentration of exogenous DPD can enhance the capacity of L. plantarum SH7 to degrade BAs and that the degradation of BAs by L. plantarum SH7 may be dependent on the LuxS /AI-2 quorum sensing (QS) system. This study provides the theoretical basis for the development of functional starter cultures of lactic acid bacteria with BA-degradation ability based on targeted LuxS /AI-2 QS system regulation and reducing the accumulation of BAs in fermented meat products .
研究领域:
微生物学
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食品科学
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生物化学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
·
2026
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IF 5.2
Jinming Dai,Chenghui Zhang,Mei Bai,Tariq Aziz,Nada K. Alharbi,Fatma Alshehri,Ashwag Shami,Fahad Saad Alhodieb,Saleh A. Alsanie,Mansour Alblaji,Haiying Cui
The quorum sensing (QS) system is a critical drug target that regulates the toxins production and biofilms formation in pathogens. This study elucidates the mechanism by which the plant polyphenol gallic acid (GA) acts as a QS inhibitor targeting the LuxS/AI-2 system in Escherichia coli O157: H7, and evaluates its potential for antibiofilm applications. Results show that GA broadly interferes with the transcription of genes in the AI-2 synthesis pathway and inhibits AI-2 production. Molecular docking combined with in vitro enzymatic inhibition assays identified LuxS as a key target of GA. Thermodynamically favored, GA binds to LuxS via hydrogen bonds and van der Waals interactions, forming a stable ground-state complex that alters the enzyme's secondary structure and inhibits its activity. Further mechanistic analysis indicates that GA induces conformational changes in the protein, reduces active site volume, and restricts key catalytic residues, thereby blocking substrate access. Under simulated meat broth conditions, GA significantly enhances the biofilm-inhibitory effect of conventional disinfectants even at subinhibitory concentrations on food-contact surfaces. These findings provide theoretical support for the potential utilization of GA as a QS-targeted antibiofilm adjuvant in the food industry.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
·
2025
·
IF 5.2
Ling Jiang,Yilin Han,Xianxuan Li,Kai Zhong,Yanping Wu,Hong Gao
This study aimed to investigate the antibiofilm activity and mechanism of licochalcone A (Lico A), a natural flavonoid compound, against biofilms of L. monocytogenes , S. aureus , and their dual-species, and evaluate the potential application of Lico A in beef. The minimum inhibitory concentration (MIC) of Lico A against both L. monocytogenes and S. aureus was 7.5 μg/mL. Crystal violet staining and confocal laser scanning microscopic analysis showed that Sub-MICs of Lico A remarkably inhibited the biofilm formation of mono- and dual-species of L. monocytogenes and S. aureus . Meanwhile, Lico A significantly reduced the extracellular polymeric substances (EPS) production and the metabolic activity of biofilms, causing decreases in surface hydrophobicity, auto-aggregation, and motility. Furthermore, Lico A inhibited autoinducer-2 signaling activity by binding to LuxS and suppressing luxS expression, which disturbed the interspecies communication and thereby impeded biofilm formation. Biofilm-related genes such as sigB , flaA , icaA , and SarA were also regulated by Lico A. Importantly, Lico A effectively inhibited the dual-species biofilms of S. aureus and L. monocytogenes on beef, decreasing by 1.1 and 1.0 log CFU/g, respectively, on day 7 of storage at 4 °C. These findings highlight the potential of Lico A as a natural antibiofilm agent, especially against mixed-species biofilms, in food industry applications.
研究领域:
食品微生物学
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抗菌剂
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生物膜研究
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群体感应
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食品保鲜
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天然化合物
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）