scholarly journals Rutin, a Natural Inhibitor of IGPD Protein, Inhibits the Biofilm Formation in Staphylococcus xylosus ATCC700404

2019 ◽  
Author(s):  
God’spower Bello-Onaghise ◽  
Xing Xiaoxu ◽  
Zhou Yonghui ◽  
Qu Qianwei ◽  
Cui Wenqiang ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Enzyme Inhibitor ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Vital Role ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Chronic Infections ◽  
Staphylococcus Xylosus ◽  
Key Enzyme

ABSTRACTThe biofilm of bacteria plays an important role in antibiotic resistance and chronic infection. Thus, in order to solve the problem of resistant bacteria, it is very important to find new drugs that can inhibit the formation of biofilms. In recent years, researchers have shifted their attention to natural products. As a flavonoid, rutin has been reported to have a variety of biological activities, interestingly, in this study, the inhibitory effect of rutin on the biofilm of Staphylococcus xylosus was investigated. We confirmed that rutin could effectively inhibit the biofilm formation of S. xylosus, then, for the sake of discussion on how it interferes with the biofilm formation, the interaction between rutin and imidazolyl phosphate dehydratase (IGPD) which has been identified as the key enzyme that plays a vital role in the process of biofilm formation was analyzed by molecular docking, the results showed that rutin had a strong affinity with IGPD, it occupied the hydrophobic cavity of the active center forming four hydrogen bonds and many other interactions. In addition, we proved that rutin was able to combine with IGPD using SPR technique. Therefore, we determined the enzyme activity and histidine content of IGPD, the result indicated that rutin could simultaneously inhibit the activity of IGPD and abrogate the synthesis of histidine. Interestingly, the hisB gene encoding for IGPD and IGPD in S. xylosus were also significantly inhibited when the bacterial culture was treated with rutin. Taken together, the results have provided evidence that rutin is a natural drug that has the ability to interfere with the formation of biofilm in S. xylosus. It is therefore a potential enzyme inhibitor of IGPD.Author’s SummaryStaphylococcus xylosus has been isolated from a variety of infections, and the biofilm formed by S. xylosus can help the bacteria evade the immune system of the host and cause chronic infections. Here, we dealt with this menace by establishing a highly effective drug with the ability to interfere with the process involved in the formation of biofilm in S. xylosus. IGPD has been reported to be directly involved in the formation of biofilm in Staphylococcus xylosus and it is known to be present in a variety of microorganisms. Based on this study, we developed a drug therapy targeting IGPD and at the same time interfere with the formation of biofilm in S. xylosus

scholarly journals Searching Hit Potential Antimicrobials in Natural Compounds Space Against Biofilm Formation

2020 ◽  
Author(s):  
Roberto Pestana ◽  
Jorge Leyva ◽  
Juvenal Yosa
Keyword(s):  
Biofilm Formation ◽  
Potential Method ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Chronic Infections ◽  
Aconitic Acid ◽  
Starting Point ◽  
In Silico Studies ◽  
Biofilm Development

Biofilms are communities of microorganisms that can colonize biotic and abiotic surfaces playing a significant role in the persistence of bacterial infection and antibiotic resistance. About 65% and 80% of microbial and chronic infections are produced by biofilm formation. The increase in infections by multi-resistant bacteria draws attention to the discovery of new drugs based on natural inhibitory molecules. The inhibition of diguanylate cyclases (DGCs), the enzyme implicated in the synthesis of the second messenger, cyclic diguanylate (c-di-GMP), involved the biofilm formation, represents a potential method for preventing the biofilm development. It has been extensively studied using PleD protein as a model of DGC for in silico studies as virtual screening and as a model for in vitro studies in biofilms formation. In the present study 224205 molecules from natural products database, ZINC15 has been evaluated through molecular docking and molecular dynamic simulation, our result suggests trans-Aconitic acid (TAA) as a possible starting point for hit-to-lead methodologies to obtain new molecules capable of inhibiting the PleD protein and hence blocking the biofilm formation.

scholarly journals Rutin, A Natural Inhibitor of IGPD Protein, Partially Inhibits Biofilm Formation in Staphylococcus xylosus ATCC700404 in vitro and in vivo

2021 ◽  
Vol 12 ◽  
Author(s):  
Qianwei Qu ◽  
Wenqiang Cui ◽  
Xiaoxu Xing ◽  
Rongfeng Zou ◽  
Xingyu Huang ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Bacterial Infections ◽  
Opportunistic Pathogen ◽  
Inhibition Mechanism ◽  
Resistant Bacteria ◽  
Glycerol Phosphate ◽  
Staphylococcus Xylosus ◽  
Key Enzyme

Staphylococcus xylosus (S. xylosus) has become an emerging opportunistic pathogen due to its strong biofilm formation ability. Simultaneously, the biofilm of bacteria plays an important role in antibiotic resistance and chronic infection. Here, we confirmed that rutin can effectively inhibit biofilm formation in S. xylosus, of which the inhibition mechanism involves its ability to interact with imidazole glycerol phosphate dehydratase (IGPD), a key enzyme in the process of biofilm formation. We designed experiments to target IGPD and inhibited its activities against S. xylosus. Our results indicated that the activity of IGPD and the amount of histidine decreased significantly under the condition of 0.8 mg/ml rutin. Moreover, the expression of IGPD mRNA (hisB) and IGPD protein was significantly down-regulated. Meanwhile, the results from molecular dynamic simulation and Bio-layer interferometry (BLI) technique showed that rutin could bind to IGPD strongly. Additionally, in vivo studies demonstrated that rutin treatment reduced inflammation and protect mice from acute mastitis caused by S. xylosus. In summary, our findings provide new insights into the treatment of biofilm mediated persistent infections and chronic bacterial infections. It could be helpful to design next generation antibiotics to against resistant bacteria.

scholarly journals Antimicrobial and Antibiofilm Peptides

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 652 ◽  
Author(s):  
Angela Di Somma ◽  
Antonio Moretta ◽  
Carolina Canè ◽  
Arianna Cirillo ◽  
Angela Duilio
Keyword(s):  
Antimicrobial Peptides ◽  
Biofilm Formation ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiofilm Activity ◽  
Chronic Infections ◽  
Planktonic Bacteria ◽  
Hostile Environments

The increasing onset of multidrug-resistant bacteria has propelled microbiology research towards antimicrobial peptides as new possible antibiotics from natural sources. Antimicrobial peptides are short peptides endowed with a broad range of activity against both Gram-positive and Gram-negative bacteria and are less prone to trigger resistance. Besides their activity against planktonic bacteria, many antimicrobial peptides also show antibiofilm activity. Biofilms are ubiquitous in nature, having the ability to adhere to virtually any surface, either biotic or abiotic, including medical devices, causing chronic infections that are difficult to eradicate. The biofilm matrix protects bacteria from hostile environments, thus contributing to the bacterial resistance to antimicrobial agents. Biofilms are very difficult to treat, with options restricted to the use of large doses of antibiotics or the removal of the infected device. Antimicrobial peptides could represent good candidates to develop new antibiofilm drugs as they can act at different stages of biofilm formation, on disparate molecular targets and with various mechanisms of action. These include inhibition of biofilm formation and adhesion, downregulation of quorum sensing factors, and disruption of the pre-formed biofilm. This review focuses on the proprieties of antimicrobial and antibiofilm peptides, with a particular emphasis on their mechanism of action, reporting several examples of peptides that over time have been shown to have activity against biofilm.

scholarly journals Searching Hit Potential Antimicrobials in Natural Compounds Space against Biofilm Formation

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5334
Author(s):  
Roberto Pestana-Nobles ◽  
Jorge A. Leyva-Rojas ◽  
Juvenal Yosa
Keyword(s):  
Natural Products ◽  
Biofilm Formation ◽  
Caulobacter Crescentus ◽  
Resistant Bacteria ◽  
Chronic Infections ◽  
Aconitic Acid ◽  
Starting Point ◽  
In Silico Studies ◽  
Biofilm Development

Biofilms are communities of microorganisms that can colonize biotic and abiotic surfaces and thus play a significant role in the persistence of bacterial infection and resistance to antimicrobial. About 65% and 80% of microbial and chronic infections are associated with biofilm formation, respectively. The increase in infections by multi-resistant bacteria instigates the need for the discovery of novel natural-based drugs that act as inhibitory molecules. The inhibition of diguanylate cyclases (DGCs), the enzyme implicated in the synthesis of the second messenger, cyclic diguanylate (c-di-GMP), involved in the biofilm formation, represents a potential approach for preventing the biofilm development. It has been extensively studied using PleD protein as a model of DGC for in silico studies as virtual screening and as a model for in vitro studies in biofilms formation. This study aimed to search for natural products capable of inhibiting the Caulobacter crescentus enzyme PleD. For this purpose, 224,205 molecules from the natural products ZINC15 database, have been evaluated through molecular docking and molecular dynamic simulation. Our results suggest trans-Aconitic acid (TAA) as a possible starting point for hit-to-lead methodologies to obtain new inhibitors of the PleD protein and hence blocking the biofilm formation.

Antimicrobial activity of seven Piper species from Colombian coffee-growing Eco-region against multidrug resistant bacteria

2020 ◽  
Vol 3 (3) ◽  
pp. 33-37
Author(s):  
Oscar M Mosquera ◽  
◽  
Roman Y. Ramirez-Rueda ◽  
Aura M. Blandon ◽  
◽  
...  
Keyword(s):  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Methanolic Extract ◽  
Biological Activities ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Biological Evaluation ◽  
Resistant Bacteria ◽  
Antibacterial Compounds ◽  
Layer Chromatography

Species of Piper genus are known for their numerous biological activities and their diverse phytochemical composition. The object of this work was to evaluate the antibacterial activity of extracts obtained from seven Piperaceae species. Broth microdilution technique was used for biological evaluation and some phytochemical nuclei present in the bioactive extracts were identified by thin layer chromatography and characterization reactions. Among the most important results, it is highlighted the inhibitory effect of the methanolic extract from Piper pesaresanum against Methicillin-resistant Staphylococcus aureus ATTC 43300, with minimum inhibitory concentration of 62.5 μg/mL. Additionally, secondary metabolites such as alkaloids, phenols and flavonoids were detected in this extract. In conclussion, the species P. pesaresanum showed high potential for bioguided search of antibacterial compounds against multidrug resistant S. aureus.

scholarly journals African Plant-Based Natural Products with Antivirulence Activities to the Rescue of Antibiotics

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 830
Author(s):  
Christian Emmanuel Mahavy ◽  
Pierre Duez ◽  
Mondher ElJaziri ◽  
Tsiry Rasamiravaka
Keyword(s):  
Natural Products ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Cell Communication ◽  
Bacterial Virulence ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
African Plants

The worldwide emergence of antibiotic-resistant bacteria and the thread of widespread superbug infections have led researchers to constantly look for novel effective antimicrobial agents. Within the past two decades, there has been an increase in studies attempting to discover molecules with innovative properties against pathogenic bacteria, notably by disrupting mechanisms of bacterial virulence and/or biofilm formation which are both regulated by the cell-to-cell communication mechanism called ‘quorum sensing’ (QS). Certainly, targeting the virulence of bacteria and their capacity to form biofilms, without affecting their viability, may contribute to reduce their pathogenicity, allowing sufficient time for an immune response to infection and a reduction in the use of antibiotics. African plants, through their huge biodiversity, present a considerable reservoir of secondary metabolites with a very broad spectrum of biological activities, a potential source of natural products targeting such non-microbicidal mechanisms. The present paper aims to provide an overview on two main aspects: (i) succinct presentation of bacterial virulence and biofilm formation as well as their entanglement through QS mechanisms and (ii) detailed reports on African plant extracts and isolated compounds with antivirulence properties against particular pathogenic bacteria.

scholarly journals Antimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Staphylococcus aureus Biofilm

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesca Berini ◽  
Viviana Teresa Orlandi ◽  
Federica Gamberoni ◽  
Eleonora Martegani ◽  
Ilaria Armenia ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Biofilm Formation ◽  
Human Cell Line ◽  
Inhibitory Effect ◽  
Resistant Bacteria ◽  
Glycopeptide Antibiotics ◽  
Targeting Therapy ◽  
External Magnet ◽  
Commensal Microbiota

In the era of antimicrobial resistance, the use of nanoconjugated antibiotics is regarded as a promising approach for preventing and fighting infections caused by resistant bacteria, including those exacerbated by the formation of difficult-to-treat bacterial biofilms. Thanks to their biocompatibility and magnetic properties, iron oxide nanoparticles (IONPs) are particularly attractive as antibiotic carriers for the targeting therapy. IONPs can direct conjugated antibiotics to infection sites by the use of an external magnet, facilitating tissue penetration and disturbing biofilm formation. As a consequence of antibiotic localization, a decrease in its administration dosage might be possible, reducing the side effects to non-targeted organs and the risk of antibiotic resistance spread in the commensal microbiota. Here, we prepared nanoformulations of the ‘last-resort’ glycopeptides teicoplanin and vancomycin by conjugating them to IONPs via surface functionalization with (3-aminopropyl) triethoxysilane (APTES). These superparamagnetic NP-TEICO and NP-VANCO were chemically stable and NP-TEICO (better than NP-VANCO) conserved the typical spectrum of antimicrobial activity of glycopeptide antibiotics, being effective against a panel of staphylococci and enterococci, including clinical isolates and resistant strains. By a combination of different methodological approaches, we proved that NP-TEICO and, although to a lesser extent, NP-VANCO were effective in reducing biofilm formation by three methicillin-sensitive or resistant Staphylococcus aureus strains. Moreover, when attracted and concentrated by the action of an external magnet, NP-TEICO exerted a localized inhibitory effect on S. aureus biofilm formation at low antibiotic concentration. Finally, we proved that the conjugation of glycopeptide antibiotics to IONPs reduced their intrinsic cytotoxicity toward a human cell line.

scholarly journals Antibacterial, Antibiofilm and Anti-Virulence Activity of Biactive Fractions from Mucus Secretion of Giant African Snail Achatina fulica against Staphylococcus aureus Strains

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1548
Author(s):  
Libardo Suárez ◽  
Andrés Pereira ◽  
William Hidalgo ◽  
Nelson Uribe
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Inhibitory Effect ◽  
Biologically Active ◽  
Mucus Secretion ◽  
New Drugs ◽  
Achatina Fulica ◽  
Mortality And Morbidity ◽  
Strong Inhibitory Effect

Staphylococcus aureus is an important etiological agent that causes skin infections, and has the propensity to form biofilms, leading to significant mortality and morbidity in patients with wounds. Mucus secretion from the Giant African snail Achatina fulica is a potential source of biologically active substances that might be an important source for new drugs to treat resistant and biofilm-forming bacteria such as S. aureus. This study evaluated the effect of semi-purified fractions from the mucus secretion of A. fulica on the growth, biofilm formation and virulence factors of S. aureus. Two fractions: FMA30 (Mw >30 kDa) and FME30 (Mw 30−10 kDa) exhibited antimicrobial activity against S. aureus with a MIC50 of 25 and 125 µg/mL, respectively. An inhibition of biofilm formation higher than 80% was observed at 9 µg/mL with FMA30 and 120 µg/mL with FME30. Furthermore, inhibition of hemolytic and protease activity was determined using a concentration of MIC20, and FME30 showed a strong inhibitory effect in the formation of clots. We report for the first time the effect of semi-purified fractions of mucus secretion of A. fulica on biofilm formation and activity of virulence factors such as α-hemolysin, coagulase and proteases produced by S. aureus strains.

Synthesis, Structure Elucidation and Biological Activities of Some Novel 4(3H)-Quinazolinones as Anti-Biofilm Agents

2019 ◽  
Vol 16 (3) ◽  
pp. 313-321
Author(s):  
Sevda Türk ◽  
Sevgi Karakuş ◽  
Abdulilah Ece ◽  
Seyhan Ulusoy ◽  
Gülgün Bosgelmez-Tınaz
Keyword(s):  
Active Site ◽  
Biofilm Formation ◽  
Structure Elucidation ◽  
Biological Activities ◽  
Opportunistic Pathogen ◽  
Docking Studies ◽  
Chronic Infections ◽  
Swarming Motility ◽  
Inhibitory Activities ◽  
Clinically Significant

Background: Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic infections in immunocompromised patients. The inhibition of Quorum Sensing (QS) system has been recognized as an attractive strategy for the treatment of P. aeruginosa infections. In the present study, a series of novel 2-methyl-3-[4-(substituedaminosulfonyl)phenyl]-4(3H)-quinazolinones (1-8) were synthesized and tested for their biofilm formation and swarming motility inhibitory activities in P. aeruginosa PA01. </P><P> Findings: These compounds were found to reduce biofilm formation by 20-32% and swarming motility by 51-62% in P. aeruginosa PA01 at a concentration of 12.5&#181;M. Molecular docking studies were also performed to elucidate the possible key interactions of these compounds with the active site of the P. aeruginosa QS receptor LasR. Furthermore, some molecular properties related to drug likeness and ADME were predicted. </P><P> Results and Conclusion: Results of this study demonstrated that compounds 1-8 can influence QS-regulated biofilm formation and swarming motility in P. aeruginosa PA01 by binding LasR protein and could be developed as anti-biofilm agents to treat chronic biofilm associated infections caused by P. aeruginosa and other clinically significant pathogens.

scholarly journals Chitooligosaccharides Modulate Glucose-Lipid Metabolism by Suppressing SMYD3 Pathways and Regulating Gut Microflora

Marine Drugs ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 69 ◽  
Author(s):  
Qiutong Wang ◽  
Yajie Jiang ◽  
Xuegang Luo ◽  
Chang Wang ◽  
Nan Wang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Glucose And Lipid Metabolism ◽  
Lipid Metabolism Disorders ◽  
Key Enzyme ◽  
Hepatocyte Steatosis ◽  
Glucagon Like Peptide 1

Chitooligosaccharides (COS) have a variety of biological activities due to their positively charged amino groups. Studies have shown that COS have antidiabetic effects, but their molecular mechanism has not been fully elucidated. The present study confirmed that COS can reduce hyperglycemia and hyperlipidemia, prevent obesity, and enhance histological changes in the livers of mice with type 2 diabetes mellitus (T2DM). Additionally, treatment with COS can modulate the composition of the gut microbiota in the colon by altering the abundance of Firmicutes, Bacteroidetes, and Proteobacteria. Furthermore, in T2DM mice, treatment with COS can upregulate the cholesterol-degrading enzymes cholesterol 7-alpha-hydroxylase (CYP7A1) and incretin glucagon-like peptide 1 (GLP-1) while specifically inhibiting the transcription and expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the key enzyme in cholesterol synthesis. Furthermore, using an oleic acid-induced hepatocyte steatosis model, we found that HMGCR can be directly transactivated by SET and MYND domain containing 3 (SMYD3), a transcriptional regulator, via 5′-CCCTCC-3′ element in the promoter. Overexpression of SMYD3 can suppress the inhibitory effect of COS on HMGCR, and COS might regulate HMGCR by inhibiting SMYD3, thereby exerting hypolipidemic functions. To the best of our knowledge, this study is the first to illustrate that COS mediate glucose and lipid metabolism disorders by regulating gut microbiota and SMYD3-mediated signaling pathways.

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