Peptide-based strategies for overcoming biofilm-associated infections: a comprehensive review.

Biofilms represent resilient microbial communities responsible for inducing chronic infections in human subjects. Given the escalating challenges associated with antibiotic therapy failures in clinical infections linked to biofilm formation, a peptide-based approach emerges as a promising alternative to effectively combat these notoriously resistant biofilms. Contrary to conventional antimicrobial peptides, which predominantly target cellular membranes, antibiofilm peptides necessitate a multifaceted approach, addressing various "biofilm-specific factors." These factors encompass Extracellular Polymeric Substance (EPS) degradation, membrane targeting, cell signaling, and regulatory mechanisms. Recent research endeavors have been directed toward assessing the potential of peptides as potent antibiofilm agents. However, to translate these peptides into viable clinical applications, several critical considerations must be meticulously evaluated during the peptide design process. This review serves to furnish an all-encompassing summary of the pivotal factors and parameters that necessitate contemplation for the successful development of an efficacious antibiofilm peptide.

An Immunomodulatory Biomimetic Single-Atomic Nanozyme for Biofilm Wound Healing Management.

Nanozyme-driven catalytic antibacterial therapy has become a promising modality for bacterial biofilm infections. However, current catalytic therapy of biofilm wounds is severely limited by insufficient catalytic efficiency, excessive inflammation, and deep tissue infection. Drawing from the homing mechanism of natural macrophages, herein, a hollow mesoporous biomimetic single-atomic nanozyme (SAN) is fabricated to actively target inflamed parts, suppress inflammatory factors, and eliminate deeply organized bacteria for enhance biofilm eradication. In the formulation, this biomimetic nanozyme (Co@SAHSs@IL-4@RCM) consists of IL-4-loaded cobalt SANs-embedded hollow sphere encapsulate by RAW 264.7 cell membrane (RCM). Upon accumulation at the infected sites through the specific receptors of RCM, Co@SAHS catalyze the conversion of hydrogen peroxide into hydroxyl radicals and are further amplify by NIR-II photothermal effect and glutathione depletion to permeate and destroy biofilm structure. This behavior subsequently causes the dissociation of RCM shell and the ensuing release of IL-4 that can reprogram macrophages, enabling suppression of oxidative injury and tissue inflammation. The work paves the way to engineer alternative "all-in-one" SANs with an immunomodulatory ability and offers novel insights into the design of bioinspired materials.

Molecular and biological characterization of pyocyanin from clinical and environmental Pseudomonas aeruginosa.

BACKGROUND: Pyocyanin is a secondary metabolite secreted by P. aeruginosa. It is a redox-active blue/green phenazine pigment that has various beneficial applications. The present study aims at screening the production of pyocyanin among clinical and environmental P. aeruginosa isolates in Dakahlya governorate, Egypt. Thereafter, large-scale production, purification, structure elucidation, and assessment of the biological activity of the highest pyocyanin producers were targeted. RESULTS: Pyocyanin from the highest clinical (PsC05) and environmental (PsE02) producers were subjected to large-scale production, followed by purification using silica gel column. Pyocyanin was characterized using TLC, UV-Vis, 1 H NMR, and FTIR spectroscopy to confirm its structure and purity. Purified pyocyanin showed remarkable antimicrobial efficacy against all tested food-borne pathogens, MDR/XDR clinically isolated bacteria and C. albicans. Furthermore, it showed a substantial effect on biofilm inhibition and eradication of pre-formed biofilm against strong biofilm producing bacterial pathogens. However, it had limited antibiofilm activity against C. albicans. Pyocyanin from PsC05 had higher antioxidant and radicals scavenging activity than that from PsE02 as determined by FRAP, DPPH, and ABTS assays. Likewise, pyocyanin from PsC05 was more active against tested cancer cell lines, especially human Breast Cancer (MCF-7) and Colorectal Carcinoma (HCT-116), than that from PsE02. More importantly, it showed minimal cytotoxicity to normal cells. CONCLUSIONS: P. aeruginosa clinical and environmental isolates produce pyocyanin pigment in varying amounts. Pyocyanin exhibits substantial anti-bacterial, and anti-fungal activity; thus, enhancing its medical applicability. It could be used to inhibit and/or eradicate biofilm from the surfaces of medical devices which is a chief source of nosocomial infections. Its antioxidant along with cytotoxic activity against cancer cell lines, make it a promising contender for use as a substitute for synthetic agents in cancer treatment.

Activities of a broad-spectrum antimicrobial peptide analogue SAMP-A4-C8 and its combat against pneumonia in Staphylococcus aureus-infected mice.

Antimicrobial peptides and their analogues have become substitutes for antibiotics in recent years. The antimicrobial peptide analogue SAMP-A4-C8 (n-octanoic-VRLLRRRI) with high antimicrobial activity was found in our lab. We speculate that it may kill pathogens by some lethal mechanism of action. In the present investigation, the microbicidal activities of SAMP-A4-C8 and its mechanism of action were investigated. The results demonstrated that SAMP-A4-C8 had lethal activities against Staphylococcus aureus and Candida albicans by cell disruption. Based on its microbicidal activities, we believe that it is worth further research for its potential as drug candidate. The results showed that SAMP-A4-C8, with low propensity to induce the resistance of S. aureus and C. albicans, could kill the persister cells of S. aureus and C. albicans, exhibited biofilm forming inhibition activity and preformed biofilm eradication ability against S. aureus and C. albicans, and displayed therapeutic potential on pneumonia in S. aureus-infected mice by reducing lung inflammation. The present study provided a promising drug candidate in the war against multidrug resistance.

Pomegranate sarcotesta lectin (PgTeL) inhibits planktonic growth and disrupts biofilm formed by Cryptococcus neoformans.

AIMS: We investigated the putative fungistatic and fungicidal activities of pomegranate sarcotesta lectin (PgTeL) against Cryptococcus neoformans B3501 (serotype D), specifically the ability of PgTeL to inhibit yeast capsule and biofilm formation in this strain. METHODS AND RESULTS: PgTeL showed a minimum inhibitory concentration of 172.0 µg ml-1, at which it did not exhibit a fungicidal effect. PgTeL concentrations of 4.0-256.0 µg ml-1 reduced biofilm biomass by 31.0%-64.0%. Furthermore, 32.0-256.0 µg ml-1 PgTeL decreased the metabolic activity of the biofilm by 32.0%-93.0%. Scanning electron microscopy images clearly revealed disruption of the biofilm matrix. Moreover, PgTeL disrupted preformed biofilms. At concentrations of 8.0-256.0 µg ml-1, PgTeL reduced metabolic activity in C. neoformans by 36.0%-92.0%. However, PgTeL did not inhibit the ability of B3501 cells to form capsules under stress conditions. CONCLUSIONS: PgTeL inhibited biofilm formation and disrupted preformed biofilms, demonstrating its potential for use as an anticryptococcal agent.

Hydrocinnamic acid and perillyl alcohol are effective against Escherichia coli biofilms when used alone and combined with antibiotics.

AIMS: The use of phytochemicals to improve the effectiveness of antibiotics is a promising strategy for the development of novel antimicrobials. In this study, the antibiofilm activity of perillyl alcohol and hydrocinnamic acid, both phytochemicals present in several plants, and two antibiotics from different classes (amoxicillin and chloramphenicol) was tested, alone and in combination, against Escherichia coli. METHODS AND RESULTS: Each molecule was tested at the minimum inhibitory concentration (MIC), 5 × MIC, and 10 × MIC, and characterized concerning biomass removal, metabolic inactivation, and cellular culturability. The highest percentages of metabolic inactivation (88.5% for 10 × MIC) and biomass reduction (61.7% for 10 × MIC) were obtained with amoxicillin. Interestingly, for 5 × MIC and 10 × MIC, phytochemicals provided a total reduction of colony-forming units (CFUs). Dual and triple combinations of phytochemicals and antibiotics (at MIC and 5 × MIC) demonstrated high efficacy in metabolic inactivation, moderate efficacy in terms of biomass reduction, and total reduction of cellular culturability for 5 × MIC. CONCLUSIONS: The results demonstrated the antibiofilm potential of phytochemicals, highlighting the advantage of phytochemical/antibiotic combinations for biofilm control.

Lactoferrin modulates the biofilm formation and bap gene expression of methicillin-resistant Staphylococcus epidermidis.

Lactoferrin is an innate glycoprotein with broad antibacterial and antibiofilm properties. The autonomous antibiofilm activity of lactoferrin against Gram-positive bacteria is postulated to involve the cell wall and biofilm components. Thus, the prevention of biomass formation and eradication of preformed biofilms by lactoferrin was investigated using a methicillin-resistant Staphylococcus epidermidis (MRSE) strain. Additionally, the ability of lactoferrin to modulate the expression of the biofilm-associated protein gene (bap) was studied. The bap gene regulates the production of biofilm-associated proteins responsible for bacterial adhesion and aggregation. In the in vitro biofilm assays, lactoferrin prevented biofilm formation and eradicated established biofilms for up to 24 and 72 h, respectively. Extensive eradication of MRSE biofilm biomass was accompanied by the significant upregulation of bap gene expression. These data suggest the interaction of lactoferrin with the biofilm components and cell wall of MRSE, including the biofilm-associated protein.

Selected antimicrobial essential oils to eradicate multi-drug resistant bacterial biofilms involved in human nosocomial infections.

Biofilms are the primary source of contamination linked to nosocomial infections by promoting bacterial resistance to antimicrobial agents, including disinfectants. Using essential oils, this study aims to inhibit and eradicate the biofilm of enterobacteria and staphylococci responsible for nosocomial infections at Guelma Hospital, northeastern Algeria. Thymbra capitata, Thymus pallescens and Artemesia herba-alba essential oils were evaluated against clinical strains of Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. The antimicrobial activity of the essential oils under consideration was assessed using an agar disc diffusion assay and the determination of minimum inhibitory concentrations (MICs). In addition, the crystal violet method and scanning electron microscopy (SEM) evaluated biofilm inhibition and eradication by those antimicrobial agents. The results indicate that T. pallescens essential oil was the most effective antimicrobial agent against pathogenic bacteria, with large zones of inhibition (up to 50 mm against S. aureus), low MICs (0.16 to 0.63 mg/mL), and powerful biofilm eradication up to 0.16 mg/mL in both 24 h and 60-min exposure times. Thus, Algerian thyme and oregano could be used in various ways to combat the biofilm that causes nosocomial infection in local hospitals.

Enhancement of Inhibition of the Pseudomonas sp. Biofilm Formation on Bacterial Cellulose-Based Wound Dressing by the Combined Action of Alginate Lyase and Gentamicin.

Bacterial biofilms generally contribute to chronic infections, including wound infections. Due to the antibiotic resistance mechanisms protecting bacteria living in the biofilm, they are a serious problem in the wound healing process. To accelerate the wound healing process and avoid bacterial infection, it is necessary to select the appropriate dressing material. In this study, the promising therapeutic properties of alginate lyase (AlgL) immobilised on BC membranes for protecting wounds from Pseudomonas aeruginosa infection were investigated. The AlgL was immobilised on never dried BC pellicles via physical adsorption. The maximum adsorption capacity of AlgL was 6.0 mg/g of dry BC, and the equilibrium was reached after 2 h. The adsorption kinetics was studied, and it has been proven that the adsorption was consistent with Langmuir isotherm. In addition, the impact of enzyme immobilisation on bacterial biofilm stability and the effect of simultaneous immobilisation of AlgL and gentamicin on the viability of bacterial cells was investigated. The obtained results showed that the AlgL immobilisation significantly reduced the amount of polysaccharides component of the P. aeruginosa biofilm. Moreover, the biofilm disruption by AlgL immobilised on BC membranes exhibited synergism with the gentamicin, resulting in 86.5% more dead P. aeruginosa PAO-1 cells.

Exposing Salmonella Senftenberg and Escherichia coli Strains Isolated from Poultry Farms to Formaldehyde and Lingonberry Extract at Low Concentrations.

European Union (EU) countries strive to improve the quality and safety of food of animal origin. Food production depends on a good microbiological quality of fodder. However, feed can be a reservoir or vector of pathogenic microorganisms, including Salmonella or Escherichia coli bacteria. Salmonella spp. and E. coli are the two most important food-borne pathogens of public health concern. Contamination with these pathogens, mainly in the poultry sector, can lead to serious food-borne diseases. Both microorganisms can form biofilms on abiotic and biotic surfaces. The cells that form biofilms are less sensitive to disinfectants, which in turn makes it difficult to eliminate them from various surfaces. Because the usage of formaldehyde in animal feed is prohibited in European countries, the replacement of this antibacterial with natural plant products seems very promising. This study aimed to assess the inhibitory effectiveness of Vaccinium vitis-idaea extract against biofilm produced by model Salmonella enterica and E. coli strains. We found that formaldehyde could effectively kill both species of bacterial cells in biofilm, while the lingonberry extract showed some antibiofilm effect on S. enterica serovar Senftenberg. In conclusion, finding natural plant products that are effective against biofilms formed by Gram-negative bacteria is still challenging.

Arginine Gemini-Based Surfactants for Antimicrobial and Antibiofilm Applications: Molecular Interactions, Skin-Related Anti-Enzymatic Activity and Cytotoxicity.

The antimicrobial and antibiofilm properties of arginine-based surfactants have been evaluated. These two biological properties depend on both the alkyl chain length and the spacer chain nature. These gemini surfactants exhibit good activity against a wide range of bacteria, including some problematic resistant microorganisms such us methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Moreover, surfactants with a C10 alkyl chain and C3 spacer inhibit the (MRSA) and Pseudomonas aeruginosa biofilm formation at concentrations as low as 8 µg/mL and are able to eradicate established biofilms of these two bacteria at 32 µg/mL. The inhibitory activities of the surfactants over key enzymes enrolled in the skin repairing processes (collagenase, elastase and hyaluronidase) were evaluated. They exhibited moderate anti-collagenase activity while the activity of hyaluronidase was boosted by the presence of these surfactants. These biological properties render these gemini arginine-based surfactants as perfect promising candidates for pharmaceutical and biological properties.

Efficacy of Organic Peroxyacids for Eliminating Biofilm Preformed by Microorganisms Isolated from Dairy Processing Plants.

The aim of this study was to evaluate the ability of microorganisms isolated from the dairy industry to form biofilms and to investigate the efficacy of organic peroxyacids (peracetic, perpropionic, and perlactic acids and BioDestroy) to eradicate those biofilms. Eighteen microorganisms were isolated from Quebec dairy processing plants that have issues associated with biofilm formation and were presumptively identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The single-species biofilm-producing ability of the isolates was then evaluated using 96-well microplates. Eight out of 18 of these isolates were identified as moderate or strong biofilm producers, and 10 out of 18 were negative or weak biofilm producers. The efficacy of the above-mentioned disinfectants was tested on the stronger biofilm-producing bacteria using the MBEC (minimum biofilm eradication concentration) assay. After 5 min, all disinfectants tested successfully eradicated both the single and mixed biofilms when applied following the recommended concentration. However, the efficacy of organic peroxyacids was significantly variable at lower concentrations. For example, 25 ppm of BioDestroy was sufficient to eradicate all the biofilms, except for Pseudomonas azotoformans PFl1A. Unfortunately, microscopic observations highlighted those dead cells were still attached to the surfaces. In conclusion, our results suggest that some microorganisms found in dairy plants can produce tenacious biofilms that are still susceptible to disinfectants, including organic peroxyacids. Further studies would be needed to confirm these observations using a dynamic method to mimic in vivo conditions. IMPORTANCE Biofilm-forming microorganisms are a major issue in the food industry, including the dairy industry, because of their negative impact on product quality. Biofilms are difficult to remove by clean-in-place (CIP) procedures commonly used in processing plants and may be less sensitive to sanitizers. Therefore, it is important to identify these microorganisms to develop biofilm control strategies. The results gathered in the present study could contribute to this aim, even though it was carried out using only static methods.

Biologically synthesized silver nanoparticles, mediated by Bothriochloa laguroides, inhibit biofilm formation and eradicate mature biofilm of Yersinia enterocolitica and Staphylococcus aureus.

AIMS: To phytosynthesize silver nanoparticles (AgNPs) and determine their antibacterial and antibiofilm capacity against gram-positive and gram-negative bacterial strains. METHODS AND RESULTS: AgNPs were synthesized using Bothriochloa laguroides aqueous extract as reducing and stabilizing agent. After characterization, a phytochemical screening to the extract and the AgNPs was performed. Antibacterial activity, inhibition and eradication of biofilms against Staphylococcus aureus and Yersinia enterocolitica strains were tested. Spherical AgNPs with an average size of 8 nm were obtained. Tannins, flavonoids, carbohydrates, proanthocyanidins, anthocyanins and saponins were identified in aqueous extract; meanwhile, only carbohydrates were identified in AgNPs. The MIC and MBC were determined at pmol L-1  levels for all tested strains. Furthermore, AgNPs inhibited more than 90% of biofilms formation and eradicated more than 80% of mature biofilms at concentrations higher than MIC. CONCLUSIONS: The AgNPs obtained in this study inhibited planktonic and sessile growth, and eradicated mature biofilms of pathogenic bacterial strains at very low concentrations. SIGNIFICANCE AND IMPACT OF STUDY: The current study showed the promising potential of AgNPs as antibiofilm agents opening the way for the future development of a new class of antibacterial products.

High-throughput assay for effect screening of amphotericin B and bioactive components on filamentous Candida albicans.

AIMS: The aim of this study was to develop a high-throughput robotic microtiter plate-based screening assay for Candida albicans, optimizing growth conditions to replicate the filamentous biofilm growth found in vivo, and subsequently, to demonstrate the assay by evaluating the effect of nutritional drinks alone and in combination with the antifungal amphotericin B (AmB). METHODS AND RESULTS: Candida albicans cultured in a defined growth medium showed filamentous growth in microcolonies, mimicking the morphology of oral mucosal disease (oral candidiasis). Addition of nutrient drinks containing fruit juices, fish oil and whey protein to the medium resulted in changed morphology and promoted growth as free yeast cells and with weak biofilm structures. Minimum inhibitory concentration of AmB on the biofilms was 0.25 µg ml-1 , and this was eightfold reduced (0.0038 µg ml-1 ) in the presence of the nutritional drinks. CONCLUSIONS: The established assay demonstrated applicability for screening of antifungal and anti-biofilm effects of bioactive substances on C. albicans biofilm with clinically relevant morphology. SIGNIFICANCE AND IMPACT OF THE STUDY: Candida albicans is the causative agent of the majority of fungal infections globally. The filamentous morphology of C. albicans and the ability to form biofilm are traits known to increase virulence and resistance towards antifungals. This study describes the development of a plate-based in vitro screening method mimicking the filamentous morphology of C. albicans found in vivo. The assay established can thus facilitate efficient antifungal drug discovery and development.

pH-switchable nanozyme cascade catalysis: a strategy for spatial-temporal modulation of pathological wound microenvironment to rescue stalled healing in diabetic ulcer.

The management of diabetic ulcer (DU) to rescue stalled wound healing remains a paramount clinical challenge due to the spatially and temporally coupled pathological wound microenvironment that features hyperglycemia, biofilm infection, hypoxia and excessive oxidative stress. Here we present a pH-switchable nanozyme cascade catalysis (PNCC) strategy for spatial-temporal modulation of pathological wound microenvironment to rescue stalled healing in DU. The PNCC is demonstrated by employing the nanozyme of clinically approved iron oxide nanoparticles coated with a shell of glucose oxidase (Fe3O4-GOx). The Fe3O4-GOx possesses intrinsic glucose oxidase (GOx), catalase (CAT) and peroxidase (POD)-like activities, and can catalyze pH-switchable glucose-initiated GOx/POD and GOx/CAT cascade reaction in acidic and neutral environment, respectively. Specifically, the GOx/POD cascade reaction generating consecutive fluxes of toxic hydroxyl radical spatially targets the acidic biofilm (pH ~ 5.5), and eradicates biofilm to shorten the inflammatory phase and initiate normal wound healing processes. Furthermore, the GOx/CAT cascade reaction producing consecutive fluxes of oxygen spatially targets the neutral wound tissue, and accelerates the proliferation and remodeling phases of wound healing by addressing the issues of hyperglycemia, hypoxia, and excessive oxidative stress. The shortened inflammatory phase temporally coupled with accelerated proliferation and remodeling phases significantly speed up the normal orchestrated wound-healing cascades. Remarkably, this Fe3O4-GOx-instructed spatial-temporal remodeling of DU microenvironment enables complete re-epithelialization of biofilm-infected wound in diabetic mice within 15 days while minimizing toxicity to normal tissues, exerting great transformation potential in clinical DU management. The proposed PNCC concept offers a new perspective for complex pathological microenvironment remodeling, and may provide a powerful modality for the treatment of microenvironment-associated diseases.

Adhesion and Anti-Adhesion Abilities of Potentially Probiotic Lactic Acid Bacteria and Biofilm Eradication of Honeybee (Apis mellifera L.) Pathogens.

Lactic acid bacteria (LAB) naturally inhabits the organisms of honeybees and can exhibit adhesive properties that protect these insects against various pathogenic microorganisms. Thus, cell surface (auto-aggregation, co-aggregation, hydrophobicity) and adhesive properties of LAB to two abiotic (polystyrene and glass) and four biotic (collagen, gelatin, mucus, and intestinal Caco-2 cells) surfaces were investigated. Additionally, anti-adhesion activity and the eradication of honeybee pathogen biofilms by LAB metabolites (culture supernatants) were determined. The highest hydrophobicity was demonstrated by Pediococcus pentosaceus 19/1 (63.16%) and auto-aggregation by Lactiplantibacillus plantarum 18/1 (71.91%). All LAB showed a broad spectrum of adhesion to the tested surfaces. The strongest adhesion was noted for glass. The ability to co-aggregate with pathogens was tested for the three most potently adherent LAB strains. All showed various levels of co-aggregation depending on the pathogen. The eradication of mature pathogen biofilms by LAB metabolites appeared to be weaker than their anti-adhesive properties against pathogens. The most potent anti-adhesion activity was observed for L. plantarum 18/1 (98.80%) against Paenibacillus apiarius DSM 5582, while the strongest biofilm eradication was demonstrated by the same LAB strain against Melissococcus plutonius DSM 29964 (19.87%). The adhesive and anti-adhesive activity demonstrated by LAB can contribute to increasing the viability of honeybee colonies and improving the conditions in apiaries.

Screening biofilm eradication activity of ethanol extracts from foodstuffs: potent biofilm eradication activity of glabridin, a major flavonoid from licorice (Glycyrrhiza glabra), alone and in combination with ɛ-poly-L-lysine.

The ethanol extracts of 155 different foodstuffs containing medicinal plants were investigated for their biofilm eradication activities against pathogenic bacteria. A combined method of a colorimetric microbial viability assay based on reduction of a tetrazolium salt (WST-8) and a biofilm formation technique on the 96-pins of a microtiter plate lid was used to screen the biofilm eradication activities of foodstuffs. The ethanol extracts of licorice (Glycyrrhiza glabra) showed potent biofilm eradication activities against Streptococcus mutans, Staphylococcus aureus, and Porphyromonas gingivalis. Among the antimicrobial constituents in licorice, glabridin had the most potent eradication activities against microbial biofilms. The minimum biofilm eradication concentration of glabridin was 25-50 µg/ml. Furthermore, the combination of glabridin with ɛ-poly-L-lysine, a food additive, could result in broad biofilm eradication activities towards a wide variety of bacteria associated with infection, including Escherichia coli and Pseudomonas aeruginosa.

Stimuli-responsive nanocarriers for bacterial biofilm treatment.

ABSTRACT: Bacterial biofilm infections have been threatening the human's life and health globally for a long time because they typically cause chronic and persistent infections. Traditional antibiotic therapies can hardly eradicate biofilms in many cases, as biofilms always form a robust fortress for pathogens inside, inhibiting the penetration of drugs. To address the issues, many novel drug carriers emerged as promising strategies for biofilm treatment. Among them, stimuli-responsive nanocarriers have attracted much attentions for their intriguing physicochemical properties, such as tunable size, shape and surface chemistry, especially smart drug release characteristic. Based on the microenvironmental difference between biofilm infection sites and normal tissue, many stimuli, such as bacterial products accumulating in biofilms (enzymes, glutathione, etc.), lower pH and higher H2O2 levels, have been employed and proved in favor of "on-demand" drug release for biofilm elimination. Additionally, external stimuli including light, heat, microwave and magnetic fields are also able to control the drug releasing behavior artificially. In this review, we summarized recent advances in stimuli-responsive nanocarriers for combating biofilm infections, and mainly, focusing on the different stimuli that trigger the drug release. 摘要: , , 。 , , 。 , , 。 , -, , , , 。 , , (, ), pHH2O2, ""。 , , , , 。 , , 。.

Elucidating the anti-biofilm and anti-quorum sensing potential of selenocystine against respiratory tract infections causing bacteria: in vitro and in silico studies.

Bacteria are increasingly relying on biofilms to develop resistance to antibiotics thereby resulting in their failure in treating many infections. In spite of continuous research on many synthetic and natural compounds, ideal anti-biofilm molecule is still not found thereby warranting search for new class of molecules. The current study focuses on exploring anti-biofilm potential of selenocystine against respiratory tract infection (RTI)-causing bacteria. Anti-bacterial and anti-biofilm assays demonstrated that selenocystine inhibits the growth of bacteria in their planktonic state, and formation of biofilms while eradicating preformed-biofilm effectively. Selenocystine at a MIC50 as low as 42 and 28 µg/mL effectively inhibited the growth of Klebsiella pneumonia and Pseudomonas aeruginosa. The antibacterial effect is further reconfirmed by agar cup diffusion assay and growth-kill assay. Selenocystine showed 30-60% inhibition of biofilm formation in K. pneumonia, and 44-70% in P. aeruginosa respectively. It also distorted the preformed-biofilms by degrading the eDNA component of the Extracellular Polymeric Substance matrix. Molecular docking studies of selenocystine with quorum sensing specific proteins clearly showed that through the carboxylic acid moiety it interacts and inhibits the protein function, thereby confirming its anti-biofilm potential. With further validation selenocystine can be explored as a potential candidate for the treatment of RTIs.

Photoresponsive Vesicles Enabling Sequential Release of Nitric Oxide (NO) and Gentamicin for Efficient Biofilm Eradication.

The development of new antibacterial agents that can efficiently eradicate biofilms is of crucial importance to combat persistent and chronic bacterial infections. Herein, the fabrication of photoresponsive vesicles capable of the sequential release of nitric oxide (NO) and gentamicin sulfate (GS) is reported, which can not only efficiently disperse Pseudomonas aeruginosa (P. aeruginosa) PAO1 biofilm but also kill the planktonic bacteria. Well-defined amphiphilic diblockcopolymers of poly(ethylene oxide)-b-poly(4-((2-nitrobenzyl)(nitroso)amino)benzyl methacrylate) (PNO) is first synthesized through atom transfer radical polymerization (ATRP). The PNO diblock copolymer self-assembled into vesicles in aqueous solution, and a hydrophilic antibiotic of GS is subsequently encapsulated into the aqueous lumens of vesicles. The vesicles undergo visible light-mediated N-NO cleavage, releasing NO and disintegrating the vesicles with the release of the GS payload. The sequential release of NO and GS efficiently eradicate P. aeruginosa PAO1 biofilm and kill the liberated bacteria, showing a better antibiofilm effect than that of NO or GS alone.