Potent Antibiofilm Agent Research Articles

Benzoic acid derivatives as potent antibiofilm agents against Klebsiella pneumoniae biofilm

Klebsiella pneumoniae is responsible for a significant proportion of human urinary tract infections, and its biofilm is a major virulence. One potential approach to controlling biofilm-associated infections is targeting the adhesin MrkD1P to disrupt biofilm formation. We employed Schrodinger's Maestro tool with the OPLS 2005 force field to dock compounds with the target protein. Two benzoic acid derivatives, 3-hydroxy benzoic acid and 2,5-dihydroxybenzoic acid, had strong binding free energies (-55.57 and-18.68kcal/mol) and were the most potent compounds. The in-vitro experiments were conducted to validate the in-silico results. The results showed that both compounds effectively inhibited biofilm formation at low concentrations (4 and 8mg/mL, respectively) and had antibiofilm activity, restricting cell attachment. Both compounds demonstrated a strong biofilm inhibitory effect, with 97% and 89% reduction in biofilm by 3-hydroxy benzoic acid and 2,5-dihydroxybenzoic acid, respectively. These findings suggest that natural compounds can be a potential source of new drugs to combat biofilm-associated infections. The study highlights the potential of targeting adhesin MrkD1P as an effective approach to controlling biofilm-associated infections caused by K.pneumoniae. The results may have implications for the development of new therapies for biofilm-associated infections and pave the way for future research in this area.

Exploring the Antimicrobial Potential and Biofilm Inhibitory Properties of Hemocyanin from Hemifusus pugilinus (Born, 1778).

The seafood industry plays a huge role in the blue economy, exploiting the advantage of the enriched protein content of marine organisms such as shrimps and molluscs, which are cultured in aquafarms. Diseases greatly affect these aquatic organisms in culture and, hence, there is need to study, in detail, their innate immune mechanisms. Hemocyanin is a non-specific innate defense molecule present in the blood cells of several invertebrates, especially molluscs, arthropods, and annelids. It is concerned with oxygen transport, blood clotting, and immune enhancement. In the present study, this macromolecular metalloprotein was isolated from the hemolymph of the marine snail Hemifusus pugilinus (Born, 1778) using Sephadex G-100 gel filtration column chromatography. It occurred as a single band (MW 80 kDa) on SDS-PAGE. High-performance liquid chromatography (HPLC) of the purified hemocyanin showed a single peak with a retention time of 4.3 min. The secondary structure and stability of the protein were detected using circular dichroism (CD), and the spectra demonstrated negative ellipticity bands close to 208 nm and 225 nm, indicating β-sheets. Further exploration of the purified hemocyanin revealed remarkable antimicrobial and antibiofilm activities against Gram-positive (Enterococcus faecalis and Staphylococcus aureus) and Gram-negative bacteria (Pseudomonas aeruginosa and Proteus vulgaris) at a concentration of 1-5 μg/mL. Spectrophotometric and in situ microscopic analyses (CLSM) unveiled the potential of the purified hemocyanin to inhibit biofilm formation in these bacteria with a minimal inhibitory concentration of 40 μg/mL. Furthermore, H. pugilinus hemocyanin (10 μg/mL concentration) displayed antifungal activity against Aspergillus niger. The purified hemocyanin was also assessed for cytotoxicity against human cancer cells using cell viability assays. Altogether, the present study shows that molluscan hemocyanin is a potential antimicrobial, antibiofilm, antifungal, anticancer, and immunomodulatory agent, with great scope for application in the enhancement of the immune system of molluscs, thereby facilitating their aquaculture.

Assessment of the growth inhibition and anti-biofilm activity of aptamer (PmA2G02) against Proteus mirabilis 1429T

Proteus mirabilis is known to cause Catheter-associated urinary tract infections (CAUTIs), which exhibit virulence factors linked to forming biofilms. Aptamers have recently been explored as potential anti-biofilm agents. This study demonstrates the anti-biofilm activity of aptamer (PmA2G02) targeting P. mirabilis 1429T, a pathogenic bacteria known to cause Catheter-associated urinary tract infections (CAUTIs). The studied aptamer inhibited biofilm formation, swarming motility, and cell viability at a concentration of 3 μM. The study also showed that the PmA2G02 had a binding affinity towards fimbrial outer membrane usher protein (PMI1466), flagellin protein (PMI1619), and regulator of swarming behavior (rsbA), which are responsible for adhesion, motility, and quorum sensing, respectively. Crystal violet assay, SEM, and confocal imaging confirmed the effectiveness of the PmA2G02 as an anti-biofilm agent. Moreover, as verified by qPCR, the expression levels of fimD, fliC2, and rsbA were significantly reduced compared to the untreated group. This study suggests that aptamer may be a potential alternative to traditional antibiotics for the treatment of CAUTIs caused by P. mirabilis. These findings shed light on the mechanisms by which the aptamer inhibits biofilm formation.

Antibiofilm Activity and Mechanism of Linalool against Food Spoilage Bacillus amyloliquefaciens.

Pellicle biofilm-forming bacteria Bacillus amyloliquefaciens are the major spoilage microorganisms of soy products. Due to their inherent resistance to antibiotics and disinfectants, pellicle biofilms formed are difficult to eliminate and represent a threat to food safety. Here, we assessed linalool's ability to prevent the pellicle of two spoilage B. amyloliquefaciens strains. The minimum biofilm inhibitory concentration (MBIC) of linalool against B. amyloliquefaciens DY1a and DY1b was 4 μL/mL and 8 μL/mL, respectively. The MBIC of linalool had a considerable eradication rate of 77.15% and 83.21% on the biofilm of the two strains, respectively. Scanning electron microscopy observations revealed that less wrinkly and thinner pellicle biofilms formed on a medium supplemented with 1/2 MBIC and 1/4 MBIC linalool. Also, linalool inhibited cell motility and the production of extracellular polysaccharides and proteins of the biofilm matrix. Furthermore, linalool exposure reduced the cell surface hydrophobicity, zeta potential, and cell auto-aggregation of B. amyloliquefaciens. Molecular docking analysis demonstrated that linalool interacted strongly with quorum-sensing ComP receptor and biofilm matrix assembly TasA through intermolecular hydrogen bonds, hydrophobic contacts, and van der Waals forces interacting with site residues. Overall, our findings suggest that linalool may be employed as a potential antibiofilm agent to control food spoilage B. amyloliquefaciens.

Potential of yellow gentian aqueous-ethanolic extracts to prevent Listeria monocytogenes biofilm formation on selected food contact surfaces

As a foodborne pathogen, Listeria monocytogenes could be commonly found in the food processing facilities, where forms biofilm on various food contact surfaces. Therefore, the control of L. monocytogenes biofilm formation is of key importance for improving food safety. The aim of this work was to examine the ability of yellow gentian root and leaf extracts to inhibit biofilm formation of L. monocytogenes strains at commonly used 37 °C and at ambient temperature associated with food processing plants (18 °C), on both polystyrene and stainless steel. Crystal violet staining assay revealed strong potential of the extracts to prevent biofilm formation on polystyrene at 37 °C (up to 90% inhibition), and on both surfaces at 18 °C (up to 78.1% and 62.9% on polystyrene and stainless steel, respectively). Antibiofilm effect could be ascribed to extracts’ ability to reduce the production of exopolysaccharides and to suppress swimming motility. Finally, qRT-PCR demonstrated no activity against quorum sensing, but up-regulation of the genes (flaA, sigB) involved in biofilm formation, most likely as a response to stressful conditions. Results obtained suggest yellow gentian extracts as potent antibiofilm agents, but further analyses are needed to determine the underlie mechanism and to validate the efficiency and safety in commercial environment.

A frog-derived antimicrobial peptide as a potential anti-biofilm agent in combating Staphylococcus aureus skin infection.

Staphylococcus aureus (S. aureus), one of the most prevalent bacteria found in atopic dermatitis lesions, can induce ongoing infections and inflammation by downregulating the expression of host defence peptides in the skin. In addition, the emergence of the 'superbug' Methicillin-resistant S. aureus (MRSA) has made the treatment of these infections more challenging. Antimicrobial peptides (AMPs), due to their potent antimicrobial activity, limited evidence of resistance development, and potential immunomodulatory effects, have gained increasing attention as potential therapeutic agents for atopic dermatitis. In this study, we report a novel AMP, brevinin-1E-OG9, isolated from the skin secretions of Odorrana grahami, which shows potent antibacterial activity, especially against S. aureus. Based on the characteristics of the 'Rana Box', we designed a set of brevinin-1E-OG9 analogues to explore its structure-activity relationship. Brevinin-1E-OG9c-De-NH2 exhibited the most potent antimicrobial efficacy in both in vitro and ex vivo studies and attenuated inflammatory responses induced by lipoteichoic acid and heat-killed microbes. As a result, brevinin-1E-OG9c-De-NH2 might represent a promising candidate for the treatment of S. aureus skin infections.

Phytic Acid Demonstrates Rapid Antibiofilm Activity and Inhibits Biofilm Formation When Used as a Surface Conditioning Agent.

Root canal infections are associated with biofilms and are treated with chemical irrigants with a high success rate. However, treatment failure does arise, which is attributed primarily to resistance exhibited by biofilms. Currently used irrigants in root canal treatment have disadvantages, and there is therefore a need for more biocompatible alternatives with antibiofilm properties to reduce root canal treatment failure and complications. The aim of this study was to evaluate the in vitro antibiofilm properties of phytic acid (IP6), which is a potential alternative treatment agent. Single- and dual-species biofilms of Enterococcus faecalis and Candida albicans were developed on the well surfaces of 12-well plates and on hydroxyapatite (HA) coupons, and then exposed to IP6. In addition, selected HA coupons were preconditioned with IP6 before biofilm development. IP6 demonstrated bactericidal effects and altered the metabolic activity of biofilm cells. Confocal laser-scanning microscopy showed that IP6 caused significant and rapid reduction in live biofilm cells. At sublethal concentrations, IP6 did not alter the expression of tested virulence genes except for C. albicans hwp1, the expression of which was upregulated but not reflected by a change in hyphal transformation. IP6-preconditioned HA coupons led to extensive inhibition of dual-species biofilm formation. The results of this study highlight for the first time the antibiofilm inhibitory properties of IP6 and the potential for its exploitation in several clinical applications. IMPORTANCE Root canal infections are biofilm associated, and despite mechanical and chemical treatment procedures, infection recurrence occurs, and this is likely due to the high tolerance of associated biofilms to antimicrobials. The currently used treatment agents have several disadvantages, which necessitates the search for new improved agents. In this study, the natural chemical phytic acid was found to exhibit antibiofilm activity against established mono and dual mature biofilms over a short contact time. Most importantly, phytic acid was found to cause significant inhibition of dual-species biofilm formation when used as a surface preconditioning agent. The findings of this study identified a novel use of phytic acid as a potential antibiofilm agent that can be used in several clinical applications.

Design, Synthesis and Evaluation of a Series of Zinc(II) Complexes of Anthracene-Affixed Multifunctional Organic Assembly as Potential Antibacterial and Antibiofilm Agents against Methicillin-Resistant Staphylococcus aureus

A novel class of zinc(II)-based metal complexes, i.e., [Zn2(acdp)(μ-Cl)]·2H2O (1), [Zn2(acdp)(μ-NO3)]·2H2O (2), and [Zn2(acdp)(μ-O2CCF3)]·2H2O (3) (Cl- = chloride; NO3- = nitrate; CF3CO2- = trifluoroacetate) of anthracene-affixed multifunctional organic assembly, H3acdp (H3acdp = N,N'-bis[anthracene-2-ylmethyl]-N,N'-bis[carboxymethyl]-1,3-diaminopropan-2-ol), have emerged as promising antibacterial and antibiofilm agents in the domain of medicinal chemistry. Accordingly, complexes 1-3 were synthesized by utilizing H3acdp in combination with ZnCl2, Zn(NO3)2·6H2O, and Zn(CF3CO2)2·H2O respectively, in the presence of NaOH at ambient temperature. The complexation between H3acdp and Zn2+ was delineated by a combined approach of spectrophotometric and spectrofluorometric titration studies. The stoichiometry of acdp3-/Zn2+ in all three complexes is observed to be 1:2, as confirmed by spectrophotometric/spectrofluorometric titration data. Elemental analysis (C, H, N, Zn), molar conductance, FTIR, UV-vis, and thermoanalytical (TGA/DTA) data were effectively used to characterize these complexes. Besides, the structures of 1-3 were established by density functional theory (DFT) calculation using B3LYP/6-311G, specifying a self-assembled compact geometry with average Zn···Zn separation of 3.4629 Å. All three zinc complexes exhibited significantly high antibacterial and antibiofilm activity against methicillin-resistant Staphylococcus aureus (MRSA BAA1717). However, complex 1 showed a more recognizable activity than 2 and 3, with minimum inhibitory concentration (MIC) values of 200, 350, and 450 μg/mL, respectively. The antimicrobial activity was tested by employing the minimum inhibitory concentration (MIC) and time-kill assay. The crystal violet (CV) assay and microscopic study were performed to examine the antibiofilm activity. As observed, complexes 1-3 had an effect on the production of extracellular polymeric substance (EPS), biofilm cell-viability, and other virulence factors such as staphyloxanthin and hemolysin production, autoaggregation ability, and microbial cell-surface hydrophobicity. Reactive oxygen species (ROS) generated due to inhibition of staphyloxanthin production in response to 1-3 were also analyzed. Moreover, complexes 1-3 showed an ability to damage the bacterial cell membrane due to accumulation of ROS resulting in DNA leakage. In addition, complexes 1-3 displayed a synergistic/additive activity with a commercially available antibiotic drug, vancomycin, with enhanced antibacterial activity. On the whole, our investigation disclosed that complex 1 could be a promising drug lead and attract much attention to medicinal chemists compared to 2 and 3 from therapeutic aspects.

Optimization and Physicochemical Characterization of Polysaccharide Purified from Sonneratia caseolaris Mangrove Leaves: a Potential Antioxidant and Antibiofilm Agent.

The Box-Behnken design was applied to determine the optimal parameters of the extraction condition by using the response surface methodology (RSM) from the leaves of Sonneratia caseolaris L. The result indicates the best-optimized conditions used for the extraction of polysaccharides at 84.02°C temperature, 3.12h time, and 27.31mL/g for the water-to-material ratio. The maximum experimental yield of 8.81 ± 0.09% was obtained which is in agreement with the predicted value of 8.79%. Thereafter, low molecular weight polysaccharide (SCLP) was separated after sequentially being purified through column chromatography with a relative molecular weight of 3.74kDa. The physicochemical properties were evaluated by characterization techniques such as FT-IR spectra, NMR spectrum, and SEM analysis. RP-HPLC analysis confirmed that SCLP was a heteropolysaccharide, majorly comprising rhamnose (28.25%), and xylose (27.17%) residues, followed by mannose (18.90%), and galactose (17.17%), respectively. Thermal analysis (TGA-DSC) results showed that SCLP is a highly thermostable polymer with a degradation temperature of 361.63°C. X-ray diffraction patterns and tertiary structure analyses indicate that SCLP had a semi-crystalline polymer having a triple-helical configuration. Moreover, SCLP displayed potential antibiofilm ability for all the tested pathogens while stronger activity against Klebsiella pneumoniae and Pseudomonas aeruginosa. In addition, SCLP has potential in vitro antioxidant activity on DPPH, ABTS radical, superoxide, and Fe2+ chelating. These findings indicate that the polysaccharide has potentially been used in functional food, cosmetics, and pharmacological industries.

The Antibacterial Activity of Palm Oil (Elaeis guineensis) Leaf Extracts against Staphylococcus aureus

Plants offer a rich source of antimicrobial agents and bioactive compounds. In this study, aqueous palm oil leaves extracts (POLE) have been used as an alternative antibacterial agent against oral infections mainly caused by S. aureus. Many previous studies report the potential use of palm oil leaf extracts in treating bacterial infections such as Escherichia coli, Salmonella species, Pseudomonas aeruginosa and Bacillus species. However, few studies have been reported on the effect of palm oil leaves extract on oral microbes. Agar diffusion method, minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) assay were conducted to observe the antibacterial activity of aqueous palm oil leaves extract. The crystal violet assay was used to determine the anti-biofilm activity of the extracts. For agar diffusion method, the diameter of inhibition zone was measured. The inhibition zone of the tested bacteria was observed between 0-20 mm. The MIC and MBC values for the tested bacteria were 3.906 mg/mL and 7.813 mg/mL respectively. While for anti-biofilm assays, aqueous POLE extract acts as a potent anti-biofilm agent with dual actions, preventing and eradicating the biofilm of the tested bacteria. In conclusion, we suggest that the aqueous POLE extract may serve as alternative natural antibacterial and anti-biofilm agent against oral infections.

The Assessment of Antimicrobial and Anti-Biofilm Activity of Essential Oils against Staphylococcus aureus Strains.

The increase in antimicrobial resistance and tolerance over the years has become a serious public health problem, leading to the inevitable development of alternative antimicrobial agents as substitutes for industrial pharmaceutical antibiotics targeting humans and animals under the concept of one health. Essential oils (EOs) extracted from aromatic and pharmaceutical plants incorporate several bioactive compounds (phytochemicals) that positively affect human and animal health. Herein, this work aimed to examine a standardized chemical composition and screen the antimicrobial and anti-biofilm activity of Thymus sibthorpii, Origanum vulgare, Salvia fruticosa, and Crithmum maritimum EOs against three different Staphylococcus aureus strains by gold-standard disc diffusion, broth microdilution, and microtiter plate biofilm assays. Therefore, the evaluation of the above-mentioned EOs were considered as substitutes for antibiotics to combat the ever-mounting antimicrobial resistance problem. The observed bacterial growth inhibition varied significantly depending on the type and concentration of the antimicrobials. Thymus sibthorpii was determined as the strongest antimicrobial, with 0.091 mg/mL minimum inhibitory concentration (MIC) and a 14-33 mm diameter inhibition zone at 5% (v/v) concentration. All tested EOs indicated almost 95% inhibition of biofilm formation at their half MIC, while gentamicin sulfate did not show sufficient anti-biofilm activity. None of the methicillin-resistant strains showed resistance to the EOs compared to methicillin-sensitive strains. Thymus sibthorpii and Origanum vulgare could be potential alternatives as antimicrobial agents to overcome the problem of microbial resistance. The tested EOs might be incorporated into antimicrobial products as safe and potent antimicrobial and anti-biofilm agents.

Alkyl Gallates as Potential Antibiofilm Agents: A Review

Biofilms, which consist of microorganisms embedded in a polymer-rich matrix, contribute to a variety of infections and increase antimicrobial resistance. Thus, there is a constant need to develop new chemotherapeutic agents to combat biofilms. This review article focuses on the use of alkyl gallates, gallic acid and its esters (methyl, ethyl, propyl, butyl, hexyl, octyl, and dodecyl gallate), most of which are found in plants, to inhibit biofilm formation. The studies under review reveal that alkyl gallates have the capacity to prevent biofilm development and eradicate mature biofilms through mechanisms that suppress the synthesis of the extracellular polymeric matrix, inhibit quorum-sensing signaling, and alter the microbial cell membrane. The effects are stronger the greater the length of the alkyl chain. Moreover, the alkyl gallates' preventive activity against biofilm formation occurs at doses below the minimum inhibitory concentration. More importantly, combining alkyl gallates with antimicrobials or blue-light irradiation produces a synergistic effect on the inhibition of biofilm formation that can be used to treat infections and overcome microbial resistance.

Beyond the Risk of Biofilms: An Up-and-Coming Battleground of Bacterial Life and Potential Antibiofilm Agents

Microbial pathogens and their virulence factors like biofilms are one of the major factors which influence the disease process and its outcomes. Biofilms are a complex microbial network that is produced by bacteria on any devices and/or biotic surfaces to escape harsh environmental conditions and antimicrobial effects. Due to the natural protective nature of biofilms and the associated multidrug resistance issues, researchers evaluated several natural anti-biofilm agents, including bacteriophages and their derivatives, honey, plant extracts, and surfactants for better destruction of biofilm and planktonic cells. This review discusses some of these natural agents that are being put into practice to prevent biofilm formation. In addition, we highlight bacterial biofilm formation and the mechanism of resistance to antibiotics.

Neem leaf extract as a Potential antibiofilm and anti ESBLS agent for K. pneumoniae

K. pneumoniae is well known for its ability to form biofilm on indwelling medical devices. These biofilms are difficult to remove because of their high tolerance to conventional antibiotics. Therefore, there is a need to look for alternative agents such as medicinal plants, which can eradicate or inhibit biofilm effectively. This study evaluated the role of neem in inhibiting ESPLs production and biofilm formation by K. pneumoniae. Factors contributing to adherence and biofilm formation were also studied. Results demonstrated that neem leaves extract was quite effective in disrupting formation of biofilms and ESBLS activity at P- value: . Moreover, the level of exopolysaccharide, which contributes to biofilm formation, was also affected significantly. Results confirm the effectiveness of neem extract in inhibiting biofilm formation. Such studies can lead to the discovery of safe antimicrobial drugs from natural sources without the risk of resistance".

A Scientometric analysis on Antibiofilm Agents developed against Pseudomonas aeruginosa

Development of therapeutic agents against a model organism like P.aeruginosa, which forms biofilms, has been reviewed in the current study. A scientometric analysis has been used to predict the developments in Pseudomonas biofilm research, to configure potential antibiofilm agents (ABA) that can have prominent inhibition or dispersal effect and also overcome the problem of drug resistance. Diversity of ABA, antibiofilm strategy, prominent investigators and institutions in Pseudomonas biofilm research during the period 2009-2019 are the areas of focus, to understand the contributions in antibiofilm therapy. Scientometric study and the meta-analysis from 25,113 research publications, indicate nanoparticles as most promising control in biofilm based hazard. The results of investigation among majority of research groups reveal prominence of combinatorial strategy in targeting biofilms. A major shift from conventional antibiotics to nanoparticles as potential ABA is one of the significant findings of the study. Co-word analysis and Sankey plots were instrumental to identify the network of strategies focusing on biofilm inhibition. A Pearson correlation analysis for percentage of biofilm inhibition shows significant relevance with the nanoparticle type but not size. Moreover the impact of antibiofilm activity could be significantly correlated with source, nature and method of synthesis.

Efficacy of bile juice mediated Cu@MWCNT nanostructure, with respect to antibacterial and antibiofilm activity

In the present study, Multi-walled carbon nanotubes (MWCNTs) were decorated with the novel green synthesized bile juice-mediated copper nanoparticle. The antimicrobial activity of BJ-Cu@MWCNT was evaluated against S. aureus and P. aeruginosa with Minimum inhibitory concentration (MIC) value of 24 and 16 µg/mL, respectively. Extensive experimental initiatives were taken to explore the mechanism of bacterial death. The synthesized nanostructure also exhibited excellent antibiofilm properties against the same bacterial strains. The findings suggest that the synthesized nanomaterial could be a potent antibacterial and antibiofilm agent against pathogenic Gram-negative and Gram-positive bacteria.

In Vitro and In Vivo Antibiofilm Activity of Red Onion Scales: An Agro-Food Waste

Red onion wastes (ROW) are valuable sources of bioactive metabolites with promising antimicrobial effects. Methicillin-resistant Staphylococcus aureus (MRSA) infections are a growing risk in hospitals and communities. This study aims to investigate the in vitro and in vivo antibiofilm activities of the acidified ethanolic extract of red onion scales (RO-T) and its fractions against an MRSA vaginal colonization model. The RO-T extract, as well as its anthocyanin-rich fraction (RO-P) and flavonoid-rich fraction (RO-S), recorded a promising antibacterial activity against highly virulent strains of bacteria (MRSA, Acinetobacter baumannii, Escherichia coli and Pseudomonas aeruginosa). RO-S showed the highest antibacterial activity (MBC of 0.33 ± 0.11 mg/mL) against MRSA USA300 and significantly eradicated its biofilm formation with an IC50 of 0.003. Using a rat model, in vivo assessment on all samples, which were formulated as a hydrogel, revealed a significant reduction of MRSA bacterial load recovered from an infected vagina compared to that of the negative control group (NCG). RO-T extract and vancomycin groups recorded the highest antibacterial activity with a bacterial load 2.998 and 3.358 logs lower than the NCG, respectively. The histopathological investigation confirmed our findings. RO-T and RO-S were standardized for their quercetin content. Finally, ROW offers a new potent antibiofilm agent mostly due to its high quercetin content.

N-benzylimidazoles as potential antimicrobial and antibiofilm agents – syntheses, bioactivity and molecular docking studies

Biofilm formation has been identified as one of the major pathways by which pathogens evade the effect of antimicrobial agents, leading to drug resistance in general. The imidazole ring provides a promising scaffold for the design of viable antimicrobial agents. In this work, halogenated benzyl derivatives of imidazole were synthesized and evaluated for antimicrobial and anti-biofilm activity. Molecular docking was used to analyse interactions between the compounds and the transcriptional regulator protein, LasR - a major protein that has downstream effect on biofilm formation in Pseudomonas aeruginosa. Results from the study revealed the marked potency of the halogenated compounds as antimicrobial agents. Antimicrobial susceptibility tests showed that the bromo- derivatives were very active against Gram-positive bacteria. The chloro- derivatives, on the other hand portrayed, a broad spectrum of antimicrobial activity. Notably, N-2-chlorobenzyl imidazole appeared to be the most potent antimicrobial agent with an MIC of 0.250 mg/mL against P. aeruginosa. Despite the relatively low antimicrobial effects displayed by the fluoro- derivatives, N-3-fluorobenzyl imidazole was identified to be a very good anti-biofilm agent with 5.3 µg/mL of the compound needed to inhibit biofilm formation by 50% (BIC50). Furthermore, all the compounds inhibited biofilms produced by Pseudomonas aeruginosa at sub-MIC concentrations. Predictions from molecular docking studies suggest that the compounds may not target the LasR protein in eliciting their anti-biofilm property.

Human Milk Oligosaccharides as Potential Antibiofilm Agents: A Review

Surface-associated bacterial communities called biofilms are ubiquitous in nature. Biofilms are detrimental in medical settings due to their high tolerance to antibiotics and may alter the final pathophysiological outcome of many healthcare-related infections. Several innovative prophylactic and therapeutic strategies targeting specific mechanisms and/or pathways have been discovered and exploited in the clinic. One such emerging and original approach to dealing with biofilms is the use of human milk oligosaccharides (HMOs), which are the third most abundant solid component in human milk after lactose and lipids. HMOs are safe to consume (GRAS status) and act as prebiotics by inducing the growth and colonization of gut microbiota, in addition to strengthening the intestinal epithelial barrier, thereby protecting from pathogens. Moreover, HMOs can disrupt biofilm formation and inhibit the growth of specific microbes. In the present review, we summarize the potential of HMOs as antibacterial and antibiofilm agents and, hence, propose further investigations on using HMOs for new-age therapeutic interventions.

Bacterial nanocellulose and long-chain fatty acids interaction

Chronic wounds are a big challenge in contemporary society, as they lead to a decrease in life-quality, amputations and even death. Infections and biofilm formation might occur with chronic wounds, due to the higher susceptibility to antibiotic multi-resistant bacteria. In this situation, novel wound dressing biomaterials are needed for treatment. Thus, the aim of this research was to evaluate a possible BNC interaction with tucumã oil/butter-derived fatty acids, as this system could be a promising biomaterial for wound treating. The interaction between cellobiose (BNC basic unit) and four fatty acids was evaluated by ab initio simulations and density functional theory (DFT), through SIESTA code. Molecular docking was also used to investigate the effect of a possible releasing of the studied fatty acids to the quorum-sensing proteins of Pseudomonas aeruginosa (gram-negative bacterium) and Staphylococcus aureus (gram-positive bacterium). According to ab initio simulations, the interaction between cellobiose and fatty acids derived from tucumã oil/butter was suggested due to physical adsorption (energy around 0.17-1.33 eV) of the lipidic structures into cellobiose. A great binding affinity (∆G ranging from 4.2-8.2 kcal.mol-1) was observed for both protonated and deprotonated fatty acids against P. aeruginosa (LasI, LasA and Rhlr) and S. aureus (ArgA and ArgC) quorum-sensing proteins, indicating that these bioactive compounds might act as potential antimicrobial and/or antibiofilm agents in the proposed system. Hence, from a theoretical viewpoint, the proposed system could be a promising raw biomaterial in the production of chronic wound dressings.