Effects of metformin on Streptococcus suis LuxS/AI-2 quorum sensing system and biofilm formation

Zuo, Jing; Shen, Yamin; Wang, Haikun; Gao, Shuji; Yuan, Shuo; Dong, Song; Wang, Yuxin; Wang, Yang

doi:10.1016/j.micpath.2023.106183

Cited by 13 publications

(6 citation statements)

References 37 publications

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“…Molecular docking is a powerful tool that can be used to evaluate the binding affinity between small molecules and proteins, reflecting changes in enzyme activity ( Zuo et al., 2023 ). To test the feasibility of our hypothesis, we conducted molecular docking experiments to assess the interaction between DZ2002 and the predicted active site of S-adenosylhomocysteine hydrolase in both PAO1 and human-derived.…”

Section: Discussionmentioning

confidence: 99%

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In vitro inhibition of Pseudomonas aeruginosa PAO1 biofilm formation by DZ2002 through regulation of extracellular DNA and alginate production

Dai,

Luo,

et al. 2024

Front. Cell. Infect. Microbiol.

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IntroductionPseudomonas aeruginosa (P. aeruginosa) is a common pathogen associated with biofilm infections, which can lead to persistent infections. Therefore, there is an urgent need to develop new anti-biofilm drugs. DZ2002 is a reversible inhibitor that targets S-adenosylhomocysteine hydrolase and possesses anti-inflammatory and immune-regulatory activities. However, its anti-biofilm activity has not been reported yet.Methods and resultsTherefore, we investigated the effect of DZ2002 on P. aeruginosa PAO1 biofilm formation by crystal violet staining (CV), real-time quantitative polymerase chain reaction (RT-qPCR) and confocal laser scanning microscopy (CLSM). The results indicated that although DZ2002 didn’t affect the growth of planktonic PAO1, it could significantly inhibit the formation of mature biofilms. During the inhibition of biofilm formation by DZ2002, there was a parallel decrease in the synthesis of alginate and the expression level of alginate genes, along with a weakening of swarming motility. However, these results were unrelated to the expression of lasI, lasR, rhII, rhIR. Additionally, we also found that after treatment with DZ2002, the biofilms and extracellular DNA content of PAO1 were significantly reduced. Molecular docking results further confirmed that DZ2002 had a strong binding affinity with the active site of S-adenosylhomocysteine hydrolase (SahH) of PAO1.DiscussionIn summary, our results indicated that DZ2002 may interact with SahH in PAO1, inhibiting the formation of mature biofilms by downregulating alginate synthesis, extracellular DNA production and swarming motility. These findings demonstrate the potential value of DZ2002 in treating biofilm infections associated with P. aeruginosa.

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Section: Discussionmentioning

confidence: 99%

“…Molecular docking is a powerful tool that can be used to evaluate the binding affinity between small molecules and proteins, reflecting changes in enzyme activity (Zuo et al, 2023). To test the feasibility of our hypothesis, we conducted molecular docking experiments to…”

Section: Discussionmentioning

confidence: 99%

In vitro inhibition of Pseudomonas aeruginosa PAO1 biofilm formation by DZ2002 through regulation of extracellular DNA and alginate production

Dai,

Luo,

et al. 2024

Front. Cell. Infect. Microbiol.

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“…Studies have shown that a high level of expression of SLY is associated with a high level of pathogenicity of the strain; moreover, the deletion of the sly gene can significantly reduce the mortality of mice [ 46 ]. ef , fabps and gap are adhesion-related genes [ 47 , 48 ], and the down-regulation of these genes indicates that floxuridine may inhibit the adhesion function of S. suis . Furthermore, a molecular docking assay was performed to verify the inhibitory effects of floxuridine on the SLY gene, and seven potential binding sites were demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Antibacterial and Antivirulence Activities of Floxuridine against Streptococcus suis

Li,

Han,

et al. 2023

IJMS

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Streptococcus suis is an emerging zoonotic pathogen that can cause fatal diseases such as meningitis and sepsis in pigs and human beings. The overuse of antibiotics is leading to an increased level of resistance in S. suis, and novel antimicrobial agents or anti-virulence agents for the treatment of infections caused by S. suis are urgently needed. In the present study, we investigated the antibacterial activity, mode of action and anti-virulence effects of floxuridine against S. suis. Floxuridine showed excessive antibacterial activity against S. suis both in vivo and in vitro; 4 × MIC of floxuridine could kill S. suis within 8 h in a time–kill assay. Meanwhile, floxuridine disrupted the membrane structure and permeability of the cytoplasmic membrane. Molecular docking revealed that floxuridine and SLY can be directly bind to each other. Moreover, floxuridine effectively inhibited the hemolytic capacity and expression levels of the virulence-related genes of S. suis. Collectively, these results indicate that the FDA-approved anticancer drug floxuridine is a promising agent and a potential virulence inhibitor against S. suis.

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“…Ten microliters of collected supernatant were added to 90 microliters of V. harveyi BB170 bacterial suspension, incubated at 30°C for 5 hours, and the luminescence intensity was measured using a multi-function fluorescence microplate analyzer. AI-2 signal molecule activity was expressed as luminescence value as described previously ( Zuo et al., 2023 ). The ratio of luminescence value between the experimental group and the blank control group was calculated as relative luminescence value.…”

Section: Methodsmentioning

confidence: 99%

Study on the inhibition activity and mechanism of Tanreqing against Klebsiella pneumoniae biofilm formation in vitro and in vivo

Zhang,

He,

Kong

et al. 2024

Front. Cell. Infect. Microbiol.

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ObjectiveTo evaluate the antibacterial effect of Tanreqing (TRQ) against K. pneumoniae and its inhibition activity on bacterial biofilm formation in vitro and in vivo, and to explore the mechanism of the inhibitory effects of TRQ on K. pneumoniae biofilm formation.MethodsAn in vitro biofilm model of K. pneumoniae was established, and the impact of TRQ on biofilm formation was evaluated using crystal violet staining and scanning electron microscopy (SEM). Furthermore, the clearance effect of TRQ against K. pneumoniae in the biofilm was assessed using the viable plate counting method; q-RT PCR was used to evaluate the inhibitory effect of different concentrations of TRQ on the expression of biofilm-related genes in Klebsiella pneumoniae; The activity of quorum sensing signal molecule AI-2 was detected by Vibrio harveyi bioluminescence assay; Meanwhile, a guinea pig lung infection model of Klebsiella pneumoniae was constructed, and after treated with drugs, pathological analysis of lung tissue and determination of bacterial load in lung tissue were performed. The treatment groups included TRQ group, imipenem(IPM) group, TRQ+IPM group, and sterile saline group as the control.ResultsThe formation of K. pneumoniae biofilm was significantly inhibited by TRQ in vitro experiments. Furthermore, when combined with IPM, the clearance of K. pneumoniae in the biofilm was notably increased compared to the TRQ group and IPM group alone. q-RT PCR analysis revealed that TRQ down-regulated the expression of genes related to biofilm formation in K. pneumoniae, specifically luxS, wbbm, wzm, and lsrK, and also inhibited the activity of AI-2 molecules in the bacterium. In vivo experiments demonstrated that TRQ effectively treated guinea pig lung infections, resulting in reduced lung inflammation. Additionally, when combined with IPM, there was a significant reduction in the bacterial load in lung tissue.ConclusionTRQ as a potential therapeutic agent plays a great role in the treatment of K. pneumoniae infections, particularly in combination with conventional antibiotics. And TRQ can enhanced the clearance effect on the bacterium by inhibiting the K. pneumoniae biofilm formation, which provided experimental evidence in support of clinical treatment of TRQ against K. pneumoniae infections.

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Effects of metformin on Streptococcus suis LuxS/AI-2 quorum sensing system and biofilm formation

Cited by 13 publications

References 37 publications

In vitro inhibition of Pseudomonas aeruginosa PAO1 biofilm formation by DZ2002 through regulation of extracellular DNA and alginate production

In vitro inhibition of Pseudomonas aeruginosa PAO1 biofilm formation by DZ2002 through regulation of extracellular DNA and alginate production

Evaluating the Antibacterial and Antivirulence Activities of Floxuridine against Streptococcus suis

Study on the inhibition activity and mechanism of Tanreqing against Klebsiella pneumoniae biofilm formation in vitro and in vivo

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