Biomolecules
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2024
·Vol. 14
·期 4
·452
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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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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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DOI
PubMed
高影响因子
Journal of Integrative Agriculture
·
2024
·
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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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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DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
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2025
·
IF 6.6
Mengchen Li,Bo Li,Binbin Long,Leibin Li,Yang Chen,Mingye Peng,Mengzhou Zhou
Lactobacillus plantarum R is the predominant bacterium widely used in food fermentation. However, it has a low tolerance to ethanol during fermentation, which restricts its broader application in the food industry. Although biofilm formation enhances bacterial resistance to various stresses, regulating biofilm formation in L. plantarum R remains challenging. In this study, we established a pathway for producing autoinducer 2 (AI-2), a quorum-sensing (QS) signaling molecule, by heterologously expressing pfs and LuxS in L. plantarum R. This approach aimed to modulate cell membrane structure and improve bacterial ethanol resistance. The findings showed that exogenous AI-2 significantly enhanced the growth of L. plantarum R under high-ethanol concentration and improved its biofilm formation at different ethanol concentrations. Furthermore, a multi-omics analysis revealed potential mechanisms by which AI-2 improved the tolerance of L. plantarum R to ethanol. Notably, the upregulation of the crr gene, a component of the phosphotransferase system (PTS), enhanced biofilm formation in response to ethanol stress. In addition, differential metabolites enriched in cysteine and methionine metabolic pathways further supported the role of QS in enhancing the tolerance of L. plantarum R to ethanol. These findings lay the groundwork for enhancing the fermentation performance of strains applied in the food fermentation industry, presenting a novel method for expanding the utilization of L. plantarum R in high-ethanol fermentation.
研究领域:
微生物学
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食品生物技术
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分子生物学
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系统生物学
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合成生物学
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发酵技术
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产品关联
DOI
高影响因子
Food Bioscience
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2024
·
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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DOI
高影响因子
JOURNAL OF FOOD PROTECTION
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2014
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IF 1.797
Hongmei Zhang,Wenyuan Zhou,Wenyan Zhang,Anlin Yang,Yanlan Liu,Yan Jiang,Shaosong Huang,Jianyu Su
Biofilms are significant hazards in the food industry. In this study, we investigated the effects of food additive such as citral, cinnamaldehyde, and tea polyphenols on mixed biofilm formation by foodborne Staphylococcus aureus and Salmonella serotype Enteritidis. The adhesion rates of mixed strains in sub-MIC of additives were determined by a microtiter plate assay and bacterial communication signal autoinducer 2 (AI-2) production via a bioluminescence reporter Vibrio harveyi BB170. The structure of mixed biofilm was analyzed using scanning electron microscopy. The effect of the disinfectants hydrogen peroxide, sodium hypochlorite, and peracetic acid was tested on the mixed biofilm. Our results demonstrated that citral, cinnamaldehyde, and tea polyphenols were able to significantly inhibit mixed biofilm formation, while citral could reduce the synthesis of AI-2. Conversely, we observed a significant increase in AI-2 mediated by cinnamaldehyde. Tea polyphenols at lower concentrations induced AI-2 synthesis; however, AI-2 synthesis was significantly inhibited at higher concentrations (300 μg/ml). Food additives inhibited the adhesion of mixed bacteria on stainless steel chips and increased the sensitivity of the mixed biofilm to disinfectants. In conclusion, citral, cinnamaldehyde, and tea polyphenols had strong inhibitory effects on mixed biofilm formation and also enhanced the effect of disinfectant on mixed biofilm formation. This study provides a scientific basis for the application of natural food additives to control biofilm formation of foodborne bacteria.
研究领域:
食品科学
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微生物学
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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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高影响因子
Food Bioscience
·
2024
·
IF 4.8
Chenghui Zhang,Changzhu Li,Tariq Aziz,Metab Alharbi,Haiying Cui,Lin Lin
Food processing environments contaminated with E. coli O157 :H7 and forming biofilms will be a continuous source of contamination, leading to foodborne illness and food spoilage. Now, the main countermeasure is chemical disinfectants, but the use of disinfectants may cause the development of drug-resistant bacteria and other negative effects. Therefore, there is an urgent need to find novel antimicrobial agents. Quorum-sensing inhibitors (QSI) are a promising strategy to control biofilm formation. This study aimed to screen the optimal QSI of E. coli O157 :H7 from plant-derived small molecules by biofilm and QS inhibitory activities and to validate their effectiveness in combination with disinfectants. In addition, the inhibition mechanism of gallic acid on biofilm formation was further explored. Gallic acid was screened as the QSI of E. coli O157 :H7, and its AI-2 inhibitory activity against LuxS/AI-2 QS system reached 95.54% and 98.89% after treatment with 1/2 MIC gallic acid for 4 h and 6 h, respectively. It inhibited biofilm formation by affecting flagellar assembly, chemotaxis, and expression of adhesion factor-related genes, which interfered with the transition of bacteria from reversible to irreversible adhesion. In beef broth simulation system, the inhibition rate was greater than 90.00% in all gallic acid and benzalkonium chloride combination groups. Therefore, gallic acid can be a potential antimicrobial synergist in the food industry, combined with disinfectants to control E. coli O157 :H7 biofilms while avoiding the development of resistance.
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
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
·
2026
·
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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PubMed
高影响因子
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