A Novel Small Molecule, LCG-N25, Inhibits Oral Streptococcal Biofilm

Lyu, Xiaoying; Li, Chungen; Zhang, Jin; Wang, Liang; Jiang, Qingsong; Shui, Yusen; Cui, Lan; Luo, Youfu; Xu, Xin

doi:10.3389/fmicb.2021.654692

Cited by 8 publications

(7 citation statements)

References 42 publications

(54 reference statements)

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“…This finding showed that ultrasound irradiation could promote the release of drug from nanoparticles, improve the slow release efficiency, and effectively increase the drug concentration at the local infection site. On the other hand, the nanoparticles themselves could act as exogenous cavitation nuclei, which could enhance the cavitation effect of ultrasound and increase the bacterial biofilm permeability while promoting more drug entry into the biofilm (Yang et al, 2019;Sun et al, 2020;Lyu et al, 2021;. After ultrasound treatment, the penetration of DiI-NPs (DiI as a model drug, fluoresces red) in the biofilm was observed by CLSM.…”

Section: Discussionmentioning

confidence: 99%

Synergistic antibacterial effects of ultrasound combined nanoparticles encapsulated with cellulase and levofloxacin on Bacillus Calmette-Guérin biofilms

Zhang

Yang

et al. 2023

Front. Microbiol.

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Tuberculosis is a chronic infectious disease, the treatment of which is challenging due to the formation of cellulose-containing biofilms by Mycobacterium tuberculosis (MTB). Herein, a composite nanoparticle loaded with cellulase (CL) and levofloxacin (LEV) (CL@LEV-NPs) was fabricated and then combined with ultrasound (US) irradiation to promote chemotherapy and sonodynamic antimicrobial effects on Bacillus Calmette-Guérin bacteria (BCG, a mode of MTB) biofilms. The CL@LEV-NPs containing polylactic acid-glycolic acid (PLGA) as the shell and CL and LEV as the core were encapsulated via double ultrasonic emulsification. The synthesized CL@LEV-NPs were uniformly round with an average diameter of 196.2 ± 2.89 nm, and the zeta potential of −14.96 ± 5.35 mV, displaying high biosafety and sonodynamic properties. Then, BCG biofilms were treated with ultrasound and CL@LEV-NPs separately or synergistically in vivo and in vitro. We found that ultrasound significantly promoted biofilms permeability and activated CL@LEV-NPs to generate large amounts of reactive oxygen species (ROS) in biofilms. The combined treatment of CL@LEV-NPs and US exhibited excellent anti-biofilm effects, as shown by significant reduction of biofilm biomass value and viability, destruction of biofilm architecture in vitro, elimination of biofilms from subcutaneous implant, and remission of local inflammation in vivo. Our study suggested that US combined with composite drug-loaded nanoparticles would be a novel non-invasive, safe, and effective treatment modality for the elimination of biofilm-associated infections caused by MTB.

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Section: Discussionmentioning

confidence: 99%

Synergistic antibacterial effects of ultrasound combined nanoparticles encapsulated with cellulase and levofloxacin on Bacillus Calmette-Guérin biofilms

Zhang

Yang

et al. 2023

Front. Microbiol.

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“…The demand for novel antibiofilm agents and the research to explore their molecular mechanism have significantly increased in recent years. For instance, the LCG-N25 is a small molecule and it has been shown to have a potent activity against oral streptococcal biofilm ( 28 ). In this study, we identify a novel small-molecule compound S-342-3 that exerted a strong inhibitory activity against biofilm formation in both MRSA and MSSA clinical isolates.…”

Section: Discussionmentioning

confidence: 99%

A novel small-molecule compound S-342-3 effectively inhibits the biofilm formation of Staphylococcus aureus

Zhang,

Shen,

Zhou

et al. 2023

Microbiol Spectr

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Staphylococcus aureus is an important human pathogen in both community and hospital settings that often causes persistent and recurrent infections. The continuous emergence of multidrug-resistant strains and the lag in antibiotic development make the treatment of S. aureus more challenging. The biofilm formation of S. aureus is an important reason for persistent infection. In this study, we demonstrated that a small-molecule compound S-342-3 can effectively inhibit the biofilm formation of S. aureus . The crystal violet semi-quantitative assays revealed that at a sub-minimum inhibitory concentration of 4 µg/mL, S-342-3 reduced S. aureus biofilm mass by 57.43%, 52.14%, and 25.49%. Using confocal laser scanning microscopy, we observed that the biofilm was more incompact and less uniform upon the treatment of S-342-3. At a sub-inhibitory concentration (4 µg/mL), the S-342-3 can effectively reduce the production of polysaccharide intercellular adhesin (PIA) and suppress the initial adhesion of cells in the biofilm. Consistently, the results of RT-qPCR revealed that the expression of genes associated with biofilm formation was downregulated by S-342-3 ( P < 0.05). However, we found that treatment with S-342-3 resulted in a significant decrease in the expression of global regulatory genes agrA and sarA ( P < 0.05), which play a key role in promoting cell surface attachment and PIA production in S. aureus biofilms. Also importantly, we experimentally proved that the S-342-3 was not toxic to A549 alveolar epithelial cells and the Galleria mellonella larvae. Collectively, these results suggest that the S-342-3 may be a promising anti-biofilm drug candidate with excellent biosafety, which can be further explored for its practical application in health care. IMPORTANCE Biofilms are an important virulence factor in Staphylococcus aureus and are characterized by a structured microbial community consisting of bacterial cells and a secreted extracellular polymeric matrix. Inhibition of biofilm formation is an effective measure to control S. aureus infection. Here, we have synthesized a small molecule compound S-342-3, which exhibits potent inhibition of biofilm formation in both MRSA and MSSA. Further investigations revealed that S-342-3 exerts inhibitory effects on biofilm formation by reducing the production of polysaccharide intercellular adhesin and preventing bacterial adhesion. Our study has confirmed that the inhibitory effect of S-342-3 on biofilm is achieved by downregulating the expression of genes responsible for biofilm formation. In addition, S-342-3 is non-toxic to Galleria mellonella larvae and A549 cells. Consequently, this study demonstrates the efficacy of a biologically safe compound S-342-3 in inhibiting biofilm formation in S. aureus, thereby providing a promising antibiofilm agent for further research.

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“…LPS was extracted from 5 mL of different Xoo cultures at the same concentration of OD 600 = 0.8 using LPS extraction kit (BestBio Biotechnology Ltd., Shanghai, China). Quantification of LPS was conducted by anthrone-sulfuric method [ 33 ] with modifications. Briefly, the standard curve of saccharide was generated using anhydrous glucose, the extracted LPS (200 μL) was mixed with anthrone reagent (600 μL) (2 g/L anthrone prepared with concentrated sulfuric acid), and then the reaction mixture was heated in a water bath at 95 °C for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Resistance of Xanthomonas oryzae pv. oryzae to Lytic Phage X2 by Spontaneous Mutation of Lipopolysaccharide Synthesis-Related Glycosyltransferase

Zhang

Qian

et al. 2022

Viruses

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Phage therapy is a promising biocontrol management on plant diseases caused by bacterial pathogens due to its specificity, efficiency and environmental friendliness. The emergence of natural phage-resistant bacteria hinders the application of phage therapy. Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of the devastating bacterial leaf blight disease of rice. Here, we obtained a spontaneous mutant C2R of an Xoo strain C2 showing strong resistance to the lytic phage X2. Analysis of the C2R genome found that the CDS2289 gene encoding glycosyltransferase acquired a frameshift mutation at the 180th nucleotide site, which also leads to a premature stop mutation at the 142nd amino acid. This mutation confers the inhibition of phage adsorption through the changes in lipopolysaccharide production and structure and bacterial surface morphology. Interestingly, glycosyltransferase-deficient C2R and an insertional mutant k2289 also showed reduced virulence, suggesting the trade-off costs of phage resistance. In summary, this study highlights the role of glycosyltransferase in interactions among pathogenic bacteria, phages and plant hosts, which provide insights into balanced coevolution from environmental perspectives.

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A Novel Small Molecule, LCG-N25, Inhibits Oral Streptococcal Biofilm

Cited by 8 publications

References 42 publications

Synergistic antibacterial effects of ultrasound combined nanoparticles encapsulated with cellulase and levofloxacin on Bacillus Calmette-Guérin biofilms

Synergistic antibacterial effects of ultrasound combined nanoparticles encapsulated with cellulase and levofloxacin on Bacillus Calmette-Guérin biofilms

A novel small-molecule compound S-342-3 effectively inhibits the biofilm formation of Staphylococcus aureus

Resistance of Xanthomonas oryzae pv. oryzae to Lytic Phage X2 by Spontaneous Mutation of Lipopolysaccharide Synthesis-Related Glycosyltransferase

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