Astilbin Inhibits the Activity of Sortase A from Streptococcus mutans

Wang, Junxian; Shi, Yan; Jing, Shisong; Dong, Haisi; Wang, Dacheng; Wang, Tiedong

doi:10.3390/molecules24030465

Cited by 35 publications

(20 citation statements)

References 44 publications

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“…Imaging of S. aureus sortase deficient mutant showed that the environmental stressors such nutrient and moisture deprivation had impacted on the integrity of the cells. These heavily compromised cells S. aureus sortase deficient mutant emphasise the role the enzyme plays in producing proteins needed for the protection of bacteria from stress and in the formation of biofilm (Guiton et al 2009;Wang et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Development of a high throughput and low cost model for the study of semi-dry biofilms

et al. 2020

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The persistence of microorganisms as biofilms on dry surfaces resistant to usual terminal cleaning methods may pose an additional risk of transmission of infections.In this study, the Centre for Disease Control (CDC) dry biofilm model (DBM) was adapted into a microtiter plate format (Model 1) and replicated to create a novel in vitro model that replicates conditions commonly encountered in the healthcare environment (Model 2). Biofilms of S. aureus grown in the two models were comparable to the biofilms of the CDC DBM in terms of recovered log 10 CFU/well. Assessment of antimicrobial tolerance of biofilms grown in the two models showedModel 2 a better model for biofilm formation. Confirmation of biofilms phenotype with an extracellular matrix deficient S. aureus suggested stress tolerance through a nonmatrix defined mechanism in organisms. This study highlights the importance of conditions maintained in bacterial growth as they affect biofilm phenotype and behaviour.

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Section: Discussionmentioning

confidence: 99%

Development of a high throughput and low cost model for the study of semi-dry biofilms

et al. 2020

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“…This study was carried out avoiding the sucrose-independent adhesion method, which has been aimed mainly at blocking sortase A, a transpeptidase involved at the anchoring of cell surface proteins, including Ag I/II, through the LPXTG motif. It has been found that several molecules can reduce biofilm formation, through the inhibition of the sortase A [ 62 , 63 ], such is the case of the natural phenol curcumin, ( Curcuma longa ) with which inhibition S. mutans sortase A activity with IC50: 10 µM and an MIC of 175 µM has been reported [ 64 ]. However, despite the multiple benefits of this molecule, some toxic effects have also been evidenced related to the high doses as a result of its use as a supplement in the diet [ 40 , 41 ].…”

Section: Resultsmentioning

confidence: 99%

In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutans through Antigen I/II

Cardona

Padilla

Rivera

et al. 2020

IJMS

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Streptococcus mutans is the main early colonizing cariogenic bacteria because it recognizes salivary pellicle receptors. The Antigen I/II (Ag I/II) of S. mutans is among the most important adhesins in this process, and is involved in the adhesion to the tooth surface and the bacterial co-aggregation in the early stage of biofilm formation. However, this protein has not been used as a target in a virtual strategy search for inhibitors. Based on the predicted binding affinities, drug-like properties and toxicity, molecules were selected and evaluated for their ability to reduce S. mutans adhesion. A virtual screening of 883,551 molecules was conducted; cytotoxicity analysis on fibroblast cells, S. mutans adhesion studies, scanning electron microscopy analysis for bacterial integrity and molecular dynamics simulation were also performed. We found three molecules ZINC19835187 (ZI-187), ZINC19924939 (ZI-939) and ZINC19924906 (ZI-906) without cytotoxic activity, which inhibited about 90% the adhesion of S. mutans to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates.

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“…Astilbin produced a 49% reduction in bacterial biofilm formation at 142.1 μM, but no significant effect at 71 μM or lower concentrations. The authors consider that the biofilm inhibitory levels are much higher than IC 50 for SrtA, because of the amount of not inhibited enzyme [ 65 ]. In our opinion, the compound’s low lipophilicity and cell permeability [ 66 ] is probably the cause of this difference.…”

Section: Sortase a Inhibitorsmentioning

confidence: 99%

Targeting Bacterial Sortases in Search of Anti-virulence Therapies with Low Risk of Resistance Development

et al. 2021

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Increasingly ineffective antibiotics and rapid spread of multi- and pan-resistant bacteria represent a global health threat; hence, the need of developing new antimicrobial medicines. A first step in this direction is identifying new molecular targets, such as virulence factors. Sortase A represents a virulence factor essential for the pathogenesis of Gram-positive pathogens, some of which have a high risk for human health. We present here an exhaustive collection of sortases inhibitors grouped by relevant chemical features: vinyl sulfones, 3-aryl acrylic acids and derivatives, flavonoids, naphtoquinones, anthraquinones, indoles, pyrrolomycins, isoquinoline derivatives, aryl β-aminoethyl ketones, pyrazolethiones, pyridazinones, benzisothiazolinones, 2-phenyl-benzoxazole and 2-phenyl-benzofuran derivatives, thiadiazoles, triazolothiadiazoles, 2-(2-phenylhydrazinylidene)alkanoic acids, and 1,2,4-thiadiazolidine-3,5-dione. This review focuses on highlighting their structure–activity relationships, using the half maximal inhibitory concentration (IC50), when available, as an indicator of each compound effect on a specific sortase. The information herein is useful for acquiring knowledge on diverse natural and synthetic sortases inhibitors scaffolds and for understanding the way their structural variations impact IC50. It will hopefully be the inspiration for designing novel effective and safe sortase inhibitors in order to create new anti-infective compounds and to help overcoming the current worldwide antibiotic shortage.

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Astilbin Inhibits the Activity of Sortase A from Streptococcus mutans

Cited by 35 publications

References 44 publications

Development of a high throughput and low cost model for the study of semi-dry biofilms

Development of a high throughput and low cost model for the study of semi-dry biofilms

In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutans through Antigen I/II

Targeting Bacterial Sortases in Search of Anti-virulence Therapies with Low Risk of Resistance Development

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