Anti-biofilm Compounds Research Articles

Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis.

The ability of dermatophytes to live in communities and resist antifungal drugs may explain treatment recurrence, especially in onychomycosis. Therefore, new molecules with reduced toxicity that target dermatophyte biofilms should be investigated. This study evaluated nonyl 3,4-dihydroxybenzoate (nonyl) susceptibility and mechanism of action on planktonic cells and biofilms of T. rubrum and T. mentagrophytes. Metabolic activities, ergosterol, and reactive oxygen species (ROS) were quantified, and the expression of genes encoding ergosterol was determined by real-time PCR. The effects on the biofilm structure were visualized using confocal electron microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). T. rubrum and T. mentagrophytes biofilms were susceptible to nonyl and resistant to fluconazole, griseofulvin (all strains), and terbinafine (two strains). The SEM results revealed that nonyl groups seriously damaged the biofilms, whereas synthetic drugs caused little or no damage and, in some cases, stimulated the development of resistance structures. Confocal microscopy showed a drastic reduction in biofilm thickness, and transmission electron microscopy results indicated that the compound promoted the derangement and formation of pores in the plasma membrane. Biochemical and molecular assays indicated that fungal membrane ergosterol is a nonyl target. These findings show that nonyl 3,4-dihydroxybenzoate is a promising antifungal compound.

Bacterial capsular polysaccharides with antibiofilm activity share common biophysical and electrokinetic properties

Bacterial biofilms are surface-attached communities that are difficult to eradicate due to a high tolerance to antimicrobial agents. The use of non-biocidal surface-active compounds to prevent the initial adhesion and aggregation of bacterial pathogens is a promising alternative to antibiotic treatments and several antibiofilm compounds have been identified, including some capsular polysaccharides released by various bacteria. However, the lack of chemical and mechanistic understanding of the activity of these polymers limits their use to control biofilm formation. Here, we screen a collection of 31 purified capsular polysaccharides and first identify seven new compounds with non-biocidal activity against Escherichia coli and/or Staphylococcus aureus biofilms. We measure and theoretically interpret the electrophoretic mobility of a subset of 21 capsular polysaccharides under applied electric field conditions, and we show that active and inactive polysaccharide polymers display distinct electrokinetic properties and that all active macromolecules share high intrinsic viscosity features. Despite the lack of specific molecular motif associated with antibiofilm properties, the use of criteria including high density of electrostatic charges and permeability to fluid flow enables us to identify two additional capsular polysaccharides with broad-spectrum antibiofilm activity. Our study therefore provides insights into key biophysical properties discriminating active from inactive polysaccharides. The characterization of a distinct electrokinetic signature associated with antibiofilm activity opens new perspectives to identify or engineer non-biocidal surface-active macromolecules to control biofilm formation in medical and industrial settings.

Antibiofilm activity from endophyte bacteria, Vibrio cholerae strains, and actinomycetes isolates in liquid and solid culture

BackgroundBiofilm-associated infections are a global threat to our economy and human health; as such, development of antibiofilm compounds is an urgent need. Our previous study identified eleven environmental isolates of endophyte bacteria, actinomycetes, and two strains of Vibrio cholerae as having strong antibiofilm activity, but only tested crude extracts from liquid culture. Here we grew the same bacteria in solid culture to induce the formation of colony biofilms and the expression of genes that may ultimately produce antibiofilm compounds. This research aimed to compare antibiofilm inhibition and destruction activities between liquid and solid cultures of these eleven environmental isolates against the biofilms of representative pathogenic bacteria.ResultsWe measured antibiofilm activity using the static antibiofilm assay and crystal violet staining. The majority of our isolates exhibited higher inhibitory antibiofilm activity in liquid media, including all endophyte bacteria, V. cholerae V15a, and actinomycetes strains (CW01, SW03, CW17). However, for V. cholerae strain B32 and two actinomycetes bacteria (TB12 and SW12), the solid crude extracts showed higher inhibitory activity. Regarding destructive antibiofilm activity, many endophyte isolates and V. cholerae strains showed no significant difference between culture methods; the exceptions were endophyte bacteria isolate JerF4 and V. cholerae B32. The liquid extract of isolate JerF4 showed higher destructive activity relative to the corresponding solid culture extract, while for V. cholerae strain B32 the solid extract showed higher activity against some biofilms of pathogenic bacteria.ConclusionsCulture conditions, namely solid or liquid culture, can influence the activity of culture extracts against biofilms of pathogenic bacteria. We compared the antibiofilm activity and presented the data that majority of isolates showed a higher antibiofilm activity in liquid culture. Interestingly, solid extracts from three isolates (B32, TB12, and SW12) have a better inhibition or/and destruction antibiofilm activity compared to their liquid culture. Further research is needed to characterize the activities of specific metabolites in solid and liquid culture extracts and to determine the mechanisms of their antibiofilm actions.

Artificial Neural Network Prediction of Antiadhesion and Antibiofilm-Forming Effects of Antimicrobial Active Mushroom Extracts on Food-Borne Pathogens.

The problem of microbial biofilms has come to the fore alongside food, pharmaceutical, and healthcare industrialization. The development of new antibiofilm products has become urgent, but it includes bioprospecting and is time and money-consuming. Contemporary efforts are directed at the pursuit of effective compounds of natural origin, also known as "green" agents. Mushrooms appear to be a possible new source of antibiofilm compounds, as has been demonstrated recently. The existing modeling methods are directed toward predicting bacterial biofilm formation, not in the presence of antibiofilm materials. Moreover, the modeling is almost exclusively targeted at biofilms in healthcare, while modeling related to the food industry remains under-researched. The present study applied an Artificial Neural Network (ANN) model to analyze the anti-adhesion and anti-biofilm-forming effects of 40 extracts from 20 mushroom species against two very important food-borne bacterial species for food and food-related industries-Listeria monocytogenes and Salmonella enteritidis. The models developed in this study exhibited high prediction quality, as indicated by high r2 values during the training cycle. The best fit between the modeled and measured values was observed for the inhibition of adhesion. This study provides a valuable contribution to the field, supporting industrial settings during the initial stage of biofilm formation, when these communities are the most vulnerable, and promoting innovative and improved safety management.

Escherichia coli Nissle 1917 inhibits biofilm formation and mitigates virulence in Pseudomonas aeruginosa.

In the quest for mitigators of bacterial virulence, cell-free supernatants (CFS) from 25 human commensal and associated bacteria were tested for activity against Pseudomonas aeruginosa. Among these, Escherichia coli Nissle 1917 CFS significantly inhibited biofilm formation and dispersed extant pseudomonas biofilms without inhibiting planktonic bacterial growth. eDNA was reduced in biofilms following exposure to E. coli Nissle CFS, as visualized by confocal microscopy. E. coli Nissle CFS also showed a significant protective effect in a Galleria mellonella-based larval virulence assay when administrated 24 h before challenge with the P. aeruginosa. No inhibitory effects against P. aeruginosa were observed for other tested E. coli strains. According to proteomic analysis, E. coli Nissle CFS downregulated the expression of several P. aeruginosa proteins involved in motility (Flagellar secretion chaperone FliSB, B-type flagellin fliC, Type IV pilus assembly ATPase PilB), and quorum sensing (acyl-homoserine lactone synthase lasI and HTH-type quorum-sensing regulator rhlR), which are associated with biofilm formation. Physicochemical characterization of the putative antibiofilm compound(s) indicates the involvement of heat-labile proteinaceous factors of greater than 30 kDa molecular size.

Design, synthesis, and biological evaluation of benzoheterocyclic sulfoxide derivatives as quorum sensing inhibitors in Pseudomonas aeruginosa

Six series of benzoheterocyclic sulfoxide derivatives were designed and synthesised as Pseudomonas aeruginosa (P. aeruginosa) quorum sensing inhibitors in this paper. We experimentally demonstrated that 6b significantly inhibited the formation of P. aeruginosa PAO1 biofilm without affecting the growth. Further mechanistic studies showed that 6b affected the luminescence of quorum sensing reported strain PAO1-lasB-gfp and the production of P. aeruginosa PAO1 elastase virulence factor which was regulated by las system. These experimental results indicate that 6b acts as a quorum sensing inhibitor mainly through the las system. Furthermore, silico molecular docking studies demonstrated that 6b and the P. aeruginosa quorum sensing receptor LasR were molecularly bound via hydrogen bonding interactions. Preliminary structure-activity relationship and docking studies illustrated that 6b shows great promise as anti-biofilm compounds for further studies in order to solve the problem of microbial resistance in future.

Ephedra foeminea as a Novel Source of Antimicrobial and Anti-Biofilm Compounds to Fight Multidrug Resistance Phenotype.

Plants are considered a wealthy resource of novel natural drugs effective in the treatment of multidrug-resistant infections. Here, a bioguided purification of Ephedra foeminea extracts was performed to identify bioactive compounds. The determination of antimicrobial properties was achieved by broth microdilution assays to evaluate minimal inhibitory concentration (MIC) values and by crystal violet staining and confocal laser scanning microscopy analyses (CLSM) to investigate the antibiofilm capacity of the isolated compounds. Assays were performed on a panel of three gram-positive and three gram-negative bacterial strains. Six compounds were isolated from E. foeminea extracts for the first time. They were identified by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) analyses as the well-known monoterpenoid phenols carvacrol and thymol and as four acylated kaempferol glycosides. Among them, the compound kaempferol-3-O-α-L-(2″,4″-di-E-p-coumaroyl)-rhamnopyranoside was found to be endowed with strong antibacterial properties and significant antibiofilm activity against S. aureus bacterial strains. Moreover, molecular docking studies on this compound suggested that the antibacterial activity of the tested ligand against S. aureus strains might be correlated to the inhibition of Sortase A and/or of tyrosyl tRNA synthase. Collectively, the results achieved open interesting perspectives to kaempferol-3-O-α-L-(2″,4″-di-E-p-coumaroyl)-rhamnopyranoside applicability in different fields, such as biomedical applications and biotechnological purposes such as food preservation and active packaging.

Marine bioactive compounds as antibiofilm agent: a metabolomic approach.

The ocean is a treasure trove of both living and nonliving creatures, harboring incredibly diverse group of organisms. A plethora of marine sourced bioactive compounds are discovered over the past few decades, many of which are found to show antibiofilm activity. These are of immense clinical significance since the formation of microbial biofilm is associated with the development of high antibiotic resistance. Biofilms are also responsible to bring about problems associated with industries. In fact, the toilets and wash-basins also show degradation due to development of biofilm on their surfaces. Antimicrobial resistance exhibited by the biofilm can be a potent threat not only for the health care unit along with industries and daily utilities. Various recent studies have shown that the marine members of various kingdom are capable of producing antibiofilm compounds. Many such compounds are with unique structural features and metabolomics approaches are essential to study such large sets of metabolites. Associating holobiome metabolomics with analysis of their chemical attribute may bring new insights on their antibiofilm effect and their applicability as a substitute for conventional antibiotics. The application of computer-aided drug design/discovery (CADD) techniques including neural network approaches and structured-based virtual screening, ligand-based virtual screening in combination with experimental validation techniques may help in the identification of these molecules and evaluation of their drug like properties.

Biofilm Formation by Staphylococcus epidermidis and Its Inhibition Using Carvacrol, 2-Aminobenzemidazole, and 3-Indole Acetonitrile.

Biofilm-associated bacterial infections are problematic for physicians due to high antimicrobial resistance in biofilm-forming bacteria. Staphylococcus species, particularly Staphylococcus epidermidis, cause severe infections particularly associated with clinical implants. In this study, we have detected the biofilm formation potential of clinical S. epidermidis isolates using phenotypic and genotypic approaches in nutrient-rich and nutrient-deficient growth conditions. The Congo red agar method determined the biofilm formation potential with limited efficacy. However, the tissue culture plate method adroitly classified the isolates as strong, moderate, weak, and non-biofilm producers with five (10%) of the isolates as strong biofilm producers. Ten biofilm-associated genes were targeted, and the fruA gene was found to be the most prevalent (20%). Three antibiofilm compounds, carvacrol, 2-aminobenzemidazole, and 3-indole acetonitrile, were assessed against strong biofilm-producing S. epidermidis isolates. To the best of our knowledge, this is the first report of genotypic and phenotypic detection of biofilms formed by clinical S. epidermidis isolates from this region. The use of 3-indole acetonitrile against these biofilms and toluene as a solvent is novel. The study highlights the significance of biofilm and antibiofilm potential of the studied compounds for effective treatment and control of S. epidermidis infections.

Development of a new indole derivative dry powder for inhalation for the treatment of biofilm-associated lung infections

The aim of this work was to produce an inhalable dry powder formulation of a new anti-biofilm compound (SC38). For this purpose, chitosan was used as a polymeric carrier and l-leucine as a dispersibility enhancer. SC38 was entrapped by spray-drying into previously optimized chitosan microparticles. The final formulation was fully characterized in vitro in terms of particle morphology, particle size and distribution, flowability, aerodynamic properties, anti-biofilm activity and effects on lung cell viability. The SC38-loaded chitosan microparticles exhibited favorable aerodynamic properties with emitted and respirable fractions higher than 80 % and 45 % respectively. The optimized formulation successfully inhibited biofilm formation at microparticle concentrations starting from 20 μg/mL for methicillin-sensitive and 100 μg/mL for methicillin-resistant Staphylococcus aureus and showed a relatively safe profile in lung cells after 72 h exposure. Future in vivo tolerability and efficacy studies are needed to unravel the potential of this novel formulation for the treatment of difficult-to-treat biofilm-mediated lung infections.

Discovering the chemical profile, antimicrobial and antibiofilm potentials of the endophytic fungus Penicillium chrysogenum isolated from Artemisia judaica L. assisted with docking studies

The continuous impedance of Pseudomonas aeruginosa to traditional antibacterial drugs due to biofilm formation resulted in a growing necessity to develop effective antibiofilm formation treatments. Thus, such a study was conducted to search for the natural metabolites from the endophytic Penicillium chrysoginum AJEF2 as a source of prospective antibiofilm-forming agents. Generally, the OSMAC (one strain many compounds) approach was undertaken to ascertain that the modified potato dextrose broth (MPDB) culture displayed substantial antibacterial potential towards various human pathogenic microorganisms (MICs = 125–500 µg/mL) and exhibited a remarkable percentage of biofilm inhibition against Pseudomonas aeruginosa clinical isolates by 92.3%. LC-ESI-HRMS analysis of such extract annotated seventeen metabolites that were screened for their inhibitory biofilm formation based on molecular docking simulation on LasR protein-specific quorum sensing. Interestingly, gladiolic acid, 8‑hydroxy-6-methylxanthone-1-carboxylic acid methyl ester, cyclo(L-tryptophanyl- l -tryptophanyl), and citreoanthrasteroid A, showed acceptable interaction energies and formed significant interactions inside the LasR active site. Those results highlight endophytic Penicillium chrysoginum AJEF2 as a potential source for antibiofilm compounds. • Antimicrobial and anti-biofilm forming activities were displayed by the endophytic P. chrysogenum AJEF2 strain isolated from Artemisia judica . • LC HRMS analysis characterized structurally assorted metabolites, mainly phenolics, benzopyran, benzofuran, coumarins, polyketide, dipeptide, meroterpene, and steroids. • Molecular docking simulation on LasR protein-specific quorum sensing was done. • Gladiolic acid, 8‑hydroxy-6-methylxanthone-1-carboxylic acid methyl ester, cyclo(L-tryptophanyl- l -tryptophanyl) and citreoanthrasteroid A, were the most likely to inhibit the biofilm formation based on molecular docking studies.

Anti-biofilm activity of caffeine against uropathogenic E. coli is mediated by curli biogenesis

Biofilms are assemblages of sessile microorganisms that form an extracellular matrix around themselves and mediate attachment to surfaces. The major component of the extracellular matrix of Uropathogenic E. coli and other Enterobacteriaceae are curli fibers, making biofilms robust and resistant to antimicrobials. It is therefore imperative to screen antibiofilm compounds that can impair biofilm formation. In the present study, we investigated the curli-dependent antibiofilm activity of caffeine against UPEC strain CFT073 and commensal strain E. coli K-12MG1655.Caffeine significantly reduced the biofilm formation of both UPEC and E. coli K-12 by 86.58% and 91.80% respectively at 48 mM caffeine as determined by Crystal Violet assay. These results were further confirmed by fluorescence microscopy and Scanning Electron Microscope (SEM). Caffeine significantly reduced the cytotoxicity and survivability of UPEC. Molecular docking analysis revealed a strong interaction between caffeine and curli regulator protein (Csg D) of E. coli. The qRT-PCR data also showed significant downregulation in the expression of CsgBA and the CsgDEFG operon at both 24 mM and 48 mM caffeine. The findings revealed that caffeine could inhibit E. coli biofilm formation by regulating curli assembly and thus may be used as an alternative therapeutic strategy for the treatment of chronic E. coli biofilm-related infections.

Antibiofilm properties of bioactive compounds from Actinomycetes against foodborne and fish pathogens

In nature, bacteria can form biofilms, multi-layered structures that adhere microbial populations to solid surfaces by exopolysaccharides, proteins, and nucleic acids. In addition to causing foodborne infections, biofilms can be a major problem in aquaculture. Actinomycetes extracts have previously demonstrated antibiofilm activity against multiple foodborne and fish pathogens, and further characterization of these extracts is needed. In this study, we identified the chemical structures and antibiofilm properties of four extracts and determined the genetic similarity of the isolates to known Streptomyces isolates. We found that several extracts contained multiple antibiofilm compounds, and the antibiofilm activities of all extracts were most stable at pH 6. Furthermore, the antibiofilm inhibition and destruction activities of the isolates were stable at different temperatures. All of crude extracts demonstrated activity against biofilms formed by foodborne and fish pathogens on the surface of stainless-steel coupons as well as polystyrene that commonly used in industrial equipment. Using PCR 16S-rRNA gene and DNA sequencing analysis, the four Actinomycetes isolates were found to be 99% (1 AC), 97% (20 PM), 95% (16 PM), and 85% (18 PM) similar to Streptomyces. Biofilm structure were analyzed using Scanning Electron Microscopy coupled with Energy-Dispersive Spectrometry analysis. Coniine/(S)-2-propylpiperidine was the most active fraction of the crude extracts of the 1 AC, 20 PM, and 16 PM isolates, and piperidine, 2-(tetrahydro-2-furanyl) was most active in the 18 PM isolate.

Natural Strategies as Potential Weapons against Bacterial Biofilms.

Microbial biofilm is an aggregation of microbial species that are either attached to surfaces or organized into an extracellular matrix. Microbes in the form of biofilms are highly resistant to several antimicrobials compared to planktonic microbial cells. Their resistance developing ability is one of the major root causes of antibiotic resistance in health sectors. Therefore, effective antibiofilm compounds are required to treat biofilm-associated health issues. The awareness of biofilm properties, formation, and resistance mechanisms facilitate researchers to design and develop combating strategies. This review highlights biofilm formation, composition, major stability parameters, resistance mechanisms, pathogenicity, combating strategies, and effective biofilm-controlling compounds. The naturally derived products, particularly plants, have demonstrated significant medicinal properties, producing them a practical approach for controlling biofilm-producing microbes. Despite providing effective antibiofilm activities, the plant-derived antimicrobial compounds may face the limitations of less bioavailability and low concentration of bioactive molecules. The microbes-derived and the phytonanotechnology-based antibiofilm compounds are emerging as an effective approach to inhibit and eliminate the biofilm-producing microbes.

Hydroquinone derivatives attenuate biofilm formation and virulence factor production in Vibrio spp

Gram-negative Vibrio parahaemolyticus is a halophilic human pathogen known to be the leading cause of food poisoning associated with consuming uncooked or undercooked seafood. The increasing presence and contamination of seafood have caused serious safety concerns in food facilities. Notably, it can form biofilms on food surfaces that confer resistance to antimicrobial treatments. Therefore, in the present study, the antibacterial, antibiofilm, and antivirulence activities of hydroquinone (HQ) and its 16 derivatives were investigated against V. parahaemolyticus and V. harveyi. Representative active antibacterial and antibiofilm compounds, 2,3-dimethylhydroquinone (2,3-DMHQ) and 2,5-ditert-butylhydroquinone (DBHQ), were further examined using a crystal violet assay, biochemical reactions, live cell imaging, and scanning electron microscopy. 2,3-DMHQ with a minimum inhibitory concentration (MIC) of 20 μg/mL completely inhibited biofilm formation at a sub-MIC of 15 μg/mL. And, DBHQ with an MIC of ˃1000 μg/mL reduced biofilm formation by 70 % at sub-MIC of 25 μg/mL. Both 2,3-DMHQ and DBHQ inhibited protease and indole production as well as motility phenotypes. 2,3-DMHQ decreased fimbriae production and hydrophobicity whereas DBHQ did not. Transcriptomic studies revealed that genes related to biofilm, quorum sensing (QS), and hemolysin were downregulated. In addition, 2,3-DMHQ and DBHQ prevented biofilm formation of V. parahaemolyticus on squid surfaces and 2,3-DMHQ reduced the presence of V. parahaemolyticus in a boiled shrimp model. Toxicity assays using the Caenorhabditis elegans and seed germinations models showed that they were non-to-mildly toxic. These results suggest that 2,3-DMHQ and DBHQ possess the antimicrobial properties required to control V. parahaemolyticus planktonic and biofilm states in food production facilities.

Synthesis of the cyanobacterial halometabolite Chlorosphaerolactylate B and demonstration of its antimicrobial effect in vitro and in vivo.

Chlorosphaerolactylate B, a newly discovered antimicrobial halometabolite from the cyanobacterium Sphaerospermopsis sp. LEGE 00249 has been synthesized in three steps by using 12-bromododecanoic acid as starting material. A total of 0.5 g was produced for in vitro and in vivo antimicrobial efficacy testing. In vitro, the minimal inhibitory concentration (MIC) was estimated to be 256 mg/L for Staphylococcus aureus, while the minimal biofilm inhibitory concentration (MBIC) was estimated to be 74 mg/L. The in vivo study utilized a porcine model of implant-associated osteomyelitis. In total, 12 female pigs were allocated into 3 groups based on inoculum (n = 4 in each group). An implant cavity (IC) was drilled in the right tibia and followed by inoculation and insertion of a steel implant. All pigs were inoculated with 10 μL containing either: 11.79 mg synthetic Chlorosphaerolactylate B + 104 CFU of S. aureus (Group A), 104 CFU of S. aureus (Group B), or pure saline (Group C), respectively. Pigs were euthanized five days after inoculation. All Group B animals showed macroscopic and microscopic signs of bone infection and both tissue and implant harbored S. aureus bacteria (mean CFU on implants = 1.9 × 105). In contrast, S. aureus could not be isolated from animals inoculated with saline. In Group A, two animals had a low number of S. aureus (CFU = 6.7 × 101 and 3.8 × 101, respectively) on the implants, otherwise all Group A animals were similar to Group C animals. In conclusion, synthetic Chlorosphaerolactylate B holds potential to be a novel antimicrobial and antibiofilm compound.

Access to Anti-Biofilm Compounds from Endolichenic Fungi Using a Bioguided Networking Screening.

Endolichenic microorganisms represent a new source of bioactive natural compounds. Lichens, resulting from a symbiotic association between algae or cyanobacteria and fungi, constitute an original ecological niche for these microorganisms. Endolichenic fungi inhabiting inside the lichen thallus have been isolated and characterized. By cultivation on three different culture media, endolichenic fungi gave rise to a wide diversity of bioactive metabolites. A total of 38 extracts were screened for their anti-maturation effect on Candida albicans biofilms. The 10 most active ones, inducing at least 50% inhibition, were tested against 24 h preformed biofilms of C. albicans, using a reference strain and clinical isolates. The global molecular network was associated to bioactivity data in order to identify and priorize active natural product families. The MS-targeted isolation led to the identification of new oxygenated fatty acid in Preussia persica endowed with an interesting anti-biofilm activity against C. albicans yeasts.

Anti-biofilm effects of sinomenine against Staphylococcus aureus.

Staphylococcus aureus is a gram-positive foodborne pathogen capable of forming strong biofilms. This study identified that anti-biofilm natural compound against S. aureus. Sinomenine, a natural compound, showed significantly reduced biofilm formation (31.97-39.86%), but no effect on bacterial growth was observed. The dispersion of preformed biofilms was observed by confocal laser scanning microscopy (CLSM). qRT-PCR revealed that sinomenine treatment significantly up-regulated agrA by 3.8-fold and down-regulated icaA gene by 3.1-fold. These indicate that sinomenine treatment induces biofilm dispersal due to cell-cell adhesion, polysaccharide intercellular adhesin (PIA), and phenol-soluble modulin (PSM) peptides production. Our results suggest that sinomenine can be used as a promising agent for effectively controlling biofilm formation and dispersion, thereby making S. aureus more susceptible to the action of antimicrobial agents.

The Multifunctional Role of Poloxamer P338 as a Biofilm Disrupter and Antibiotic Enhancer: A Small Step forward against the Big Trouble of Catheter-Associated Escherichia coli Urinary Tract Infections.

Poloxamer 338 (P338), a nonionic surfactant amphiphilic copolymer, is herein proposed as an anti-biofilm compound for the management of catheter-associated urinary tract infections (CAUTIs). P338’s ability to disrupt Escherichia coli biofilms on silicone urinary catheters and to serve as antibiotic enhancer was evaluated for biofilm-producing E. coli Ec5FSL and Ec9FSL clinical strains, isolated from urinary catheters. In static conditions, quantitative biofilm formation assay allowed us to determine the active P338 concentration. In dynamic conditions, the BioFlux system, combined with confocal laser scanning microscopy, allowed us to investigate the P338 solution’s ability to detach biofilm, alone or in combination with sub-MIC concentrations of cefoxitin (FOX). The 0.5% P338 solution was able to destroy the structure of E. coli biofilms, to reduce the volume and area fraction covered by adherent cells (41.42 ± 4.79% and 56.20 ± 9.22% reduction for the Ec5FSL and Ec9FSL biofilms, respectively), and to potentiate the activity of 1\\2 MIC FOX in disaggregating biofilms (19.41 ± 7.41% and 34.66 ± 3.75% reduction in the area fraction covered by biofilm for Ec5FSL and Ec9FSL, respectively) and killing cells (36.85 ± 7.13% and 32.33 ± 4.65% increase in the biofilm area covered by dead Ec5FSL and Ec9FSL cells, respectively).

An Overview of Biofilm Formation-Combating Strategies and Mechanisms of Action of Antibiofilm Agents.

Biofilm formation on surfaces via microbial colonization causes infections and has become a major health issue globally. The biofilm lifestyle provides resistance to environmental stresses and antimicrobial therapies. Biofilms can cause several chronic conditions, and effective treatment has become a challenge due to increased antimicrobial resistance. Antibiotics available for treating biofilm-associated infections are generally not very effective and require high doses that may cause toxicity in the host. Therefore, it is essential to study and develop efficient anti-biofilm strategies that can significantly reduce the rate of biofilm-associated healthcare problems. In this context, some effective combating strategies with potential anti-biofilm agents, including plant extracts, peptides, enzymes, lantibiotics, chelating agents, biosurfactants, polysaccharides, organic, inorganic, and metal nanoparticles, etc., have been reviewed to overcome biofilm-associated healthcare problems. From their extensive literature survey, it can be concluded that these molecules with considerable structural alterations might be applied to the treatment of biofilm-associated infections, by evaluating their significant delivery to the target site of the host. To design effective anti-biofilm molecules, it must be assured that the minimum inhibitory concentrations of these anti-biofilm compounds can eradicate biofilm-associated infections without causing toxic effects at a significant rate.