Potent Antibiofilm Activity Research Articles

Antifungal and Antibiofilm Activity of Cyclic Temporin L Peptide Analogues against Albicans and Non-Albicans Candida Species.

Temporins are one of the largest families of antimicrobial peptides with both anti-inflammatory and antimicrobial activity. Herein, for a panel of cyclic temporin L isoform analogues, the antifungal and antibiofilm activities were determined against representative Candida strains, including C. albicans, C. glabrata, C. auris, C. parapsilosis and C. tropicalis. The outcomes indicated a significant anti-candida activity against planktonic and biofilm growth for four peptides (3, 7, 15 and 16). The absence of toxicity up to high concentrations and survival after infection were assessed in vivo by using Galleria mellonella larvae, and the correlation between conformation and cytotoxicity was investigated by fluorescence assays and circular dichroism (CD). By combining fluorescence spectroscopy, CD, dynamic light scattering, confocal and atomic force microscopy, the mode of action of four analogues was hypothesized. The results pinpointed that peptide 3 emerged as a non-toxic compound showing a potent antibiofilm activity and represents a promising compound for biomedical applications.

Antimicrobial properties of spray-dried cellulose nanocrystals and metal oxide-based nanoparticles-in-microspheres

Spray-dried nanoparticle-in-microsphere formulations, composed of aluminum oxide nanoparticles (NPs), zinc oxide, zinc oxide NPs and cellulose nanocrystals (CNCs), with potent antimicrobial and antibiofilm activity against Gram-negative and Gram-positive bacteria are reported. The study highlights the role of matrix compositions (ratios) in manipulating metal oxide biomaterials' antimicrobial properties and toxicity. The antimicrobial activity of nanoparticle-in-microsphere was higher than each raw material used. A formulation composed of CNCs (weight % ≥ 0.75%) and an equal weight % of aluminum oxide and zinc oxide NPs (∼ 0.25% per type of NPs) produced the highest antimicrobial and antibiofilm activity. Interestingly, the toxicity of these formulations, tested against peripheral blood mononuclear cells, was very minimal (≤500 µg/ml) and significantly lower than the toxicity of the metal oxide NPs when tested alone. Nanoparticles-in-microspheres with low toxicity and high antimicrobial properties could be employed in target drug delivery to bypass antibiotics.

Identification of Distinct Characteristics of Antibiofilm Peptides and Prospection of Diverse Sources for Efficacious Sequences.

A majority of microbial infections are associated with biofilms. Targeting biofilms is considered an effective strategy to limit microbial virulence while minimizing the development of antibiotic resistance. Toward this need, antibiofilm peptides are an attractive arsenal since they are bestowed with properties orthogonal to small molecule drugs. In this work, we developed machine learning models to identify the distinguishing characteristics of known antibiofilm peptides, and to mine peptide databases from diverse habitats to classify new peptides with potential antibiofilm activities. Additionally, we used the reported minimum inhibitory/eradication concentration (MBIC/MBEC) of the antibiofilm peptides to create a regression model on top of the classification model to predict the effectiveness of new antibiofilm peptides. We used a positive dataset containing 242 antibiofilm peptides, and a negative dataset which, unlike previous datasets, contains peptides that are likely to promote biofilm formation. Our model achieved a classification accuracy greater than 98% and harmonic mean of precision-recall (F1) and Matthews correlation coefficient (MCC) scores greater than 0.90; the regression model achieved an MCC score greater than 0.81. We utilized our classification-regression pipeline to evaluate 135,015 peptides from diverse sources for potential antibiofilm activity, and we identified 185 candidates that are likely to be effective against preformed biofilms at micromolar concentrations. Structural analysis of the top 37 hits revealed a larger distribution of helices and coils than sheets, and common functional motifs. Sequence alignment of these hits with known antibiofilm peptides revealed that, while some of the hits showed relatively high sequence similarity with known peptides, some others did not indicate the presence of antibiofilm activity in novel sources or sequences. Further, some of the hits had previously recognized therapeutic properties or host defense traits suggestive of drug repurposing applications. Taken together, this work demonstrates a new in silico approach to predicting antibiofilm efficacy, and identifies promising new candidates for biofilm eradication.

Development and evaluation of Zhumeria majdae essential oil-loaded nanoliposome against multidrug-resistant clinical pathogens causing nosocomial infection

In this study, we used Zhumeria majdae essential oil (ZMEO) loaded nanoliposome (NLP) to control several multidrug-resistant clinical pathogens (MDRs) that cause nosocomial infections using thin-layer hydration. Initially, ZMEO was extracted and analyzed by GC-MS, and then NLP-ZMEO was examined with different ratios of ZMEO to lecithin. Based on evaluation of release profile and physical stability, size distribution, and particle size, using dynamic light scattering (DLS) results, the most stable NLP-ZMEO were prepared from ZMEO to lecithin ratio 1:3 that relative to pure ZMEO presented more potent antioxidant, anti-quorum sensing, and anti-biofilm activities. The morphology results (AFM and SEM) also agreed with DLS analysis. Also, the results of structural properties (DSC and FTIR) approved interaction between ZMEO and NLP. Comparing the cytotoxic effect on fibroblasts cell lines and antibacterial activity (MIC, MBC, and agar disc diffusion method), it was found that the antimicrobial activity in NLP-ZMEO was higher than ZMEO against multidrug-resistant clinical pathogens that cause nosocomial infection. The subcytotoxic values of the tested NLP-ZMEO were higher than MICs and MBCs for MDR bacteria and chlorhexidine doses.

Modified poly(L-lysine)-based structures as novel antimicrobials for diabetic foot infections, an in-vitro study.

Background: Wound infections occur as sequelae to skin trauma and cause significant hospitalizations, morbidity and mortality. Skin traumas arise more frequently in those with diabetes or cardiovascular disease and in these settings, may be chronic with poorer outcomes including lower limb amputation. Treatment of chronic wound infection is challenging due to antibiotic resistance and biofilm formation by bacteria including S. aureus and P. aeruginosa, which are among the most frequent causative pathogens. Managing these challenging infections requires new molecules and modalities. Methods: We evaluated antimicrobial and anti-biofilm activity of star-shaped poly(L-lysine) (PLL) polymers against S. aureus and P. aeruginosa strains and clinical isolates recovered from wounds including diabetic foot wounds (DFW) in a Dublin Hospital in 2019. A star-shaped PLL polypeptide series, specifically G2(8)PLL 20, G3(16)PLL 10, G4(32)PLL 5 with variation in polypeptide chain length and arm-multiplicity, were compared to a linear peptide, PLL 160 with equivalent number of lysine residues. Results: All PLLs, including the linear polypeptide, were bactericidal at 1μM against S. aureus 25923 and P. aeruginosa PAO1, with log reduction in colony forming units/ml between 2.7-3.6. PLL 160 demonstrated similar killing potency against 20 S. aureus and five P. aeruginosa clinical isolates from DFW, mean log reductions: 3.04 ± 0.16 and 3.96 ± 0.82 respectively after 1 hour incubation. Potent anti-biofilm activity was demonstrated against S. aureus 25923 but for clinical isolates, low to moderate loss of biofilm viability was shown using PLL 160 and G3(16)PLL 10 at 50 μM ( S. aureus) and 200 μM ( P. aeruginosa) with high inter-isolate variability . In the star-shaped architecture, antimicrobial activity was retained with incorporation of 5-mer hydrophobic amino-acid modifications to the arms of the polypeptides (series G3(16)PLL 20-coPLT 5, G3(16)PLL 20-coPLI 5, G3(16)PLL 20-coPLP 5). Conclusion: These polypeptides offer structural flexibility for clinical applications and have potential for further development, particularly in the setting of diabetic foot and other chronic wound infections.

Chemical Composition and Antibacterial, Anti-biofilm and Anti-virulence Activities of Plant Extracts Against Human Pathogenic Bacteria

Background: Bacterial multi-drug resistance is one of the serious issues in the worldwide. The majority of drug resistance developed by bacteria is derived from the formation of biofilm and the production of several virulence factors. Objective: To combat the emerging drug resistance nature of bacteria, we have used some medicinal plants such as Stevia rebaudiana, Cymbopogon flexuosus, Matricaria chamomilla, Ocimum sanctum, Phyllanthus amarus and Thymus vulgaris for the extraction of active molecules that can inhibit the biofilm formation and bacterial growth. Materials & Methods: Each extracted compounds were checked for anti-bacterial, antibiofilm, and anti-virulence activities against Gram-positive and Gram-negative pathogenic bacteria. Soxhlet method of extraction was used for obtaining crude extracts. Agar disc diffusion and 96-wells microplate spectroscopic reading were used to detect the antibacterial and antibiofilm properties of extracts. Crystal violet staining was used for the detection of biofilm cells. GC-MS analysis was carried out to identify the chemical constituents present in the extracts. Results: At a concentration of 25 mg mL-1 , the highest antibacterial activities were obtained in M. chamomilla acetone extract (CHAAC) against E. coli (17.66±1.15 mm), S. Typhimurium (13.66±1.52 mm) and S. sonnei (14±1.73 mm). M. chamomilla chloroform extracted (CHACE) showed effective against S. aureus (30±2 mm) and P. aeruginosa (13.66±1.52 mm). The minimum inhibitory concentration of crude extracts derived from M. chamomilla was 0. 781mg.mL-1 against S. aureus. Furthermore, the oil extract from C. flexuosus (LEGO) exhibited significant antibacterial activity against S. aureus (at 0.781 µg mL-1 ). The potent anti-biofilm activity was observed in G. superba (KALO) against E. coli (78.6%) and S. typhimurium (79.1%), and V. negundo (VNO) against S. Typhimurium (87.3%). Furthermore, the GC-MS analysis showed the presence of active chemical constituents in the extracts which might have been effective anti-bacterial, anti-biofilm, and anti-virulence properties. Conclusion: The extracts from the medicinal plant showed antibiofilm, anti-virulence (attenuation of pyocyanin, LasA, vilacein, and swarming motility) activity towards the pathogenic bacteria. GC-MS analysis confirms the presence of an active component in the extracts. Future study is required to purify the bioactive molecules and elucidate the molecular mechanism of antibiofilm and anti-virulence properties.

Potent antibacterial and antibiofilm activities of TICbf-14, a peptide with increased stability against trypsin.

The poor stability of peptides against trypsin largely limits their development as potential antibacterial agents. Here, to obtain a peptide with increased trypsin stability and potent antibacterial activity, TICbf-14 derived from the cationic peptide Cbf-14 was designed by the addition of disulfide-bridged hendecapeptide (CWTKSIPPKPC) loop. Subsequently, the trypsin stability and antimicrobial and antibiofilm activities of this peptide were evaluated. The possible mechanisms underlying its mode of action were also clarified. The results showed that TICbf-14 exhibited elevated trypsin inhibitory activity and effectively mitigated lung histopathological damage in bacteria-infected mice by reducing the bacterial counts, further inhibiting the systemic dissemination of bacteria and host inflammation. Additionally, TICbf-14 significantly repressed bacterial swimming motility and notably inhibited biofilm formation. Considering the mode of action, we observed that TICbf-14 exhibited a potent membrane-disruptive mechanism, which was attributable to its destructive effect on ionic bridges between divalent cations and LPS of the bacterial membrane. Overall, TICbf-14, a bifunctional peptide with both antimicrobial and trypsin inhibitory activity, is highly likely to become an ideal candidate for drug development against bacteria.

Antibiofilm activity of glycolic acid and glyoxal and their diffusion–reaction interactions with biofilm components

Biofilms on food-contact surfaces act as potential reservoirs of microbial pathogens and can cause operational problems. The search for effective biofilm control agents is a significant research need. In this study, glycolic acid (GA) and glyoxal (GO) were tested in the control of biofilms formed by Bacilluscereus and Pseudomonasfluorescens. Benzalkonium chloride (BAC) and peracetic acid (PAA) were used as reference biocides for industrial surface disinfection. The action of the selected biocides was assessed in bacterial motility, culturability, biofilm removal and inactivation, interference with biofilm components and limitation of biocide penetration through the biofilms (reaction–diffusion interactions). Bacterial motility was not affected by the exposure to sub-inhibitory biocide concentrations. In terms of antibiofilm activity, B.cereus biofilms were tolerant to the action of BAC, GA, and GO, with reductions of circa 2-log CFU/cm2. Even 10000 µg/mL of PAA had modest effects against B. cereus biofilms (5-log CFU/cm2). On the other hand, P.fluorescens biofilms were more susceptible to the biocides, except BAC which was not effective. The minimum concentrations to cause 3-log CFU/cm2 reduction in P. fluorescens biofilms were 10000 µg/mL of PAA and GA, and 20000 µg/mL of GO. GO and BAC were the most actives for biofilm removal, while high biofilm inactivation was caused by GA and PAA. In general, biofilm components affected the antimicrobial activity of all the biocides. The activity of GA and GO was not notably diffusion–reaction limited in contrast to PAA. Overall, this study demonstrated that GA and GO had potential antibiofilm activity, being limited at a low level by physicochemical interactions with biofilm components.

Antibiofilm Activity of Human Milk Oligosaccharides against Multidrug Resistant and Susceptible Isolates of Acinetobacter baumannii.

Acinetobacter baumannii is a serious threat to human health, per the Centers for Disease Control and Prevention's latest threat assessment. A. baumannii is a Gram-negative opportunistic bacterial pathogen that causes severe community and nosocomial infections in immunocompromised patients. Treatment of these infections is confounded by the emergence of multi- and pan-drug resistant strains of A. baumannii. A. baumannii colonizes abiotic and biotic surfaces and evades antimicrobial challenges by forming biofilms, which are three-dimensional architectural structures of cells adhered to a substrate and encased in an extracellular matrix comprised of polymeric substances such as polysaccharides, proteins, and DNA. Biofilm-inhibiting compounds have recently gained attention as a chemotherapeutic strategy to prevent or disperse A. baumannii biofilms and restore the utility of traditional antimicrobial strategies. Recent work indicates that human milk oligosaccharides (HMOs) have potent antibacterial and biofilm-inhibiting properties. We sought to test the utility of HMOs against a bank of clinical isolates of A. baumannii to ascertain changes in bacterial growth or biofilm formation. Our results indicate that out of 18 strains tested, 14 were susceptible to the antibiofilm activities of HMOs, and that the potent antibiofilm activity was observed in strains isolated from diverse anatomical sites, disease manifestations, and across antibiotic-resistant and susceptible strains.

Novel Polyherbal Nanocolloids to Control Bovine Mastitis.

Mastitis is a widespread disease in dairy cattle occurring throughout the world. The increased use of antibiotics brings about the development of antibiotic-resistant microbes. The application of antibiotics in dairy farming led to increased antibiotic resistance and represents a major obstacle for the treatment of mastitis. Recent advancements in nanotechnology led to the development of nanocolloids to overcome disadvantages posed by conventional antimicrobial agents. Hence, a novel, environmentally friendly, cost-effective, biocompatible, and long-term antibacterial represents a promising solution for medicine and farming. Hence, polyherbal nanocolloids (PHNc) was formulated by using the extracts of Syzygium aromaticum, Cinnamomum verum, Emblica officinalis, Terminalia belerica, Terminalia chebula, and Cymbopogon citratus and physicochemically characterized. From mastitis milk samples, microorganisms were isolated including Acinetobacter junii, Klebsiella pneumoniae, Pseudomonas stutzeri, and Acinetobacter baumannii and screened for antibiotic susceptibility. All the isolated strains were tested with PHNc and compared with antibiotics. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and biofilm assays were performed at different concentrations, and antibacterial effects were quantified. In our results, PHNc showed potent bacteriostatic, bactericidal, and antibiofilm activity against all the strains. Our results indicated that PHNc can reduce the virulence factors responsible for infection by different bacterial strains. This study confirmed that PHNc had the potential to inhibit the growth of pathogenic Gram-negative and Gram-positive strains and could be utilized as an alternative to antibiotics to inhibit multidrug-resistant microbial pathogens in cattle.

Oral Minocycline As Systemic Therapy for Uncomplicated Venous Access Device-Related Bloodstream Infection with Coagulase-Negative Staphylococci in Patients after Allogeneic Hematopoietic Cell Transplantation

Venous access device-related bloodstream infections (VAD-BSIs) with coagulase-negative staphylococci (CoNS) are common complications after allogeneic hematopoietic cell transplantation (alloHCT). So far, the standard systemic antimicrobial therapy for uncomplicated VAD-BSIs with methicillin-resistant CoNS consisted of intravenous (IV) vancomycin (vanco). This approach requires hospitalization, necessitates new competent venous access, exposes patients to potential (mainly renal) toxicity and increases the risk of commensal flora dysbiosis with selection of vanco-resistant enterococci. Patients after alloHCT are particularly at risk of iatrogenic and nosocomial complications. In addition, repeated hospitalizations can impact autonomy and quality of life and are associated with significant costs.Minocycline (mino) is an oral antimicrobial agent that has strong in vitro effects on most Gram positive bacteria and potential anti-biofilm activity, and can be used in the clinic for some CoNS infections. Our infectious disease specialists proposed that systemic therapy with oral mino could be used for the management of uncomplicated VAD-BSIs, primarily when the reference treatment with IV vanco was not possible (renal failure or allergy) or when hospitalization was refused by patients. We retrospectively analyzed the results of this mino-based approach.From January 2012 to December 2020, we treated 24 uncomplicated VAD-BSIs with CoNS in 23 alloHCT patients aged 17-72y with oral mino. Uncomplicated VAD-BSIs were defined as 2 or more blood cultures positive for the same CoNS drawn consecutively peripherally and through the VAD, in patients without signs of sepsis, cellulitis or suppurative thrombophlebitis and without endovascular implant or orthopedic material. VAD were implantable ports (n=17), tunneled catheter (n=1) or PICC-lines (n=6). Pathogens were S. epidermidis (n= 21) or S. haemolyticus (n=3). CoNS were in vitro susceptible to mino according to EUCAST guidelines (with MIC <= 0.5mg/L, predominantly). Mino was administered at a dose of 100 mg BID for 7-14 days. For 8 VAD-BSIs, patients were initially treated with IV vanco for the first 1-3 days followed by oral mino, while 16 VAD-SIBs were managed with oral mino alone. VAD management consisted of catheter removal (for tunneled and PICC-lines, n=7) or antibiotic locks with vanco (n=15) or gentamicin (n=2) administered at least every other day for 14 days (for ports).Overall, clearance of bacteremia (as assessed by negativity of surveillance peripheral blood cultures with the same CoNS drawn between d+3 and +30 after initiation of systemic therapy) was achieved in all but 1 patient (with port, treated with mino alone) who had persistent bacteremia at day +9. No complication such as suppurative thrombophlebitis, endocarditis or metastatic foci of infection was observed in any patient during the 3-month period after initiation of treatment. Among the 17 patients for whom VAD salvage was attempted, VAD decontamination was successful in 10 cases while 4 patients experienced persistently positive VAD-derived blood cultures during the early (d+3 to +14) surveillance period and 3 patients experienced delayed relapse of VAD-BSIs with the same CoNS 1-3 months later (with 1 patient with cellulitis). All these events led to VAD removal. Treatment with mino was well tolerated with the exception of mild skin rash in one patient.Our results in this retrospective cohort suggest that oral mino can be a promising alternative to standard IV vanco for systemic therapy in VAD-BSIs with CoNS and that a strategy combining oral mino and antibiotic locks may salvage VAD in approximately half of the cases. This remains to be confirmed in prospective studies. DisclosuresNo relevant conflicts of interest to declare.

Consolidated antimicrobial and anticancer activities through newly synthesized novel series of pyrazoles bearing indazolylthiazole moiety: characterization and molecular docking

A new series of pyrazoles have been synthesized via 2-(3-phenyl-1,3,4,5,6,7-hexahydro-2H-indazol-2-yl)thiazol-4(5H)-one(2), which on treatment with phosphorus pentachloride and phosphoryl chloride afforded 4-chlorothiazole derivative(3). Reaction of 3 with hydrazine hydrate in boiling gave 4- hydrazineylthiazole derivative (4). Heterocyclization of 4 with aromatic aldehydes and active methylene compounds afforded the pyrazole derivatives (5-8). The synthesized pyrazoles (5–8) and their precursor (1–4) were evaluated for antimicrobial activities. All prepared compounds revealed abroad-spectrum antimicrobial activity with maximum inhibition activity against Streptococcus mutans. Compound 3 revealed the most potent antibiofilm inhibition activity against the three used pathogens. Additionally, all compounds (1-8) were also tested for cytotoxic activity against hepatoma and colon carcinoma cell lines. Compounds 3, 5 and 7 displayed good to excellent activity against all tested tumor cells with IC50 values ranged from 6.13 to 23.85 μg/ml. On the other hand, all compounds were evaluated for cytotoxic activity on normal human melanocytes cell lines and found to be signified its high selectivity toward cancer cells than normal cells. Moreover, the molecular modeling study was carried out using (MOE 2014) software. The computational studies are confirming the results in biological activity.

Cuminaldehyde exhibits potential antibiofilm activity against Pseudomonas aeruginosa involving reactive oxygen species (ROS) accumulation: a way forward towards sustainable biofilm management.

Pseudomonas aeruginosa often causes various acute and chronic infections in humans exploiting biofilm. Molecules interfering with microbial biofilm formation could be explored for the sustainable management of infections linked to biofilm. Towards this direction, the antimicrobial and antibiofilm activity of cuminaldehyde, an active ingredient of the essential oil of Cuminum cyminum was tested against Pseudomonas aeruginosa. In this regard, the minimum inhibitory concentration (MIC) of cuminaldehyde was found to be 150μg/mL against the test organism. Experiments such as crystal violet assay, estimation of total biofilm protein, fluorescence microscopy and measurement of extracellular polymeric substances (EPS) indicated that the sub-MIC doses (up to 60µg/mL) of cuminaldehyde demonstrated considerable antibiofilm activity without showing any antimicrobial activity to the test organism. Moreover, cuminaldehyde treatment resulted in substantial accumulation of cellular reactive oxygen species (ROS) that led to the inhibition of microbial biofilm formation. To this end, the exposure of ascorbic acid was found to restore the biofilm-forming ability of the cuminaldehyde-treated cells. Besides, a noticeable reduction in proteolytic activity was also observed when the organism was treated with cuminaldehyde. Taken together, the results demonstrated that cuminaldehyde could be used as a promising molecule to inhibit the biofilm formation of Pseudomonas aeruginosa.

A Novel Antimicrobial Peptide Sparamosin26-54 From the Mud Crab Scylla paramamosain Showing Potent Antifungal Activity Against Cryptococcus neoformans.

Due to the increasing prevalence of drug-resistant fungi and the limitations of current treatment strategies to fungal infections, exploration and development of new antifungal drugs or substituents are necessary. In the study, a novel antimicrobial peptide, named Sparamosin, was identified in the mud crab Scylla paramamosain, which contains a signal peptide of 22 amino acids and a mature peptide of 54 amino acids. The antimicrobial activity of its synthetic mature peptide and two truncated peptides (Sparamosin1–25 and Sparamosin26–54) were determined. The results showed that Sparamosin26–54 had the strongest activity against a variety of Gram-negative bacteria, Gram-positive bacteria and fungi, in particular had rapid fungicidal kinetics (killed 99% Cryptococcus neoformans within 10 min) and had potent anti-biofilm activity against C. neoformans, but had no cytotoxic effect on mammalian cells. The RNA-seq results showed that after Sparamosin26–54 treatment, the expression of genes involved in cell wall component biosynthesis, cell wall integrity signaling pathway, anti-oxidative stress, apoptosis and DNA repair were significantly up-regulated, indicating that Sparamosin26–54 might disrupt the cell wall of C. neoformans, causing oxidative stress, DNA damage and cell apoptosis. The underlying mechanism was further confirmed. Sparamosin26–54 could bind to several phospholipids in the cell membrane and effectively killed C. neoformans through disrupting the integrity of the cell wall and cell membrane observed by electron microscope and staining assay. In addition, it was found that the accumulation of reactive oxygen species (ROS) increased, the mitochondrial membrane potential (MMP) was disrupted, and DNA fragmentation was induced after Sparamosin26–54 treatment, which are all hallmarks of apoptosis. Taken together, Sparamosin26–54 has a good application prospect as an effective antimicrobial agent, especially for C. neoformans infections.

SILVER NANOPARTICLE INCORPORATED GEL FOR TOPICAL BACTERIAL TREATMENT

Numerous pathogenic bacteria are developing antibiotic resistance. Improvement from multidrug resistant (MDR) infections is a problematic issue and requires a multiple treatment with broad-spectrum antibiotics which are less efficient, more toxic and more expensive. Silver nanoparticles (AgNPs) are attracting much attention because of their potent antibacterial and anti-biofilm activities. These nanoparticles are lengthily synthesized and used as a successful broad spectrum antibacterial agent against Gram negative and Gram positive bacteria including antibiotic unwilling bacteria. Silver attacks multiple targets in the microorganism consequently decreases its ability to develop battle. Effect of coating on AgNPs constancy, toxicity on the microbial host and their antimicrobial activity was discussed. The amalgamation of AgNPs into hydrogels magnifies the antibacterial activity according to their characteristics; hydrogels work as an competent stabilizer of AgNPs and control the release of AgNPs. In the present review, the silver nanoparticles-hydrogel and their components as well as their antibacterial activities and wound healing efficacies are reviewed and discussed on the bases of constituent variabilities and characteristics. Different factors and topics are measured since there are challenges and challenging issues need to be faced and solved for expansion of new ideal antibacterial formulation.

Polyurethanes from Hydrophobic Elastic Materials to Hydrogels with Potent Nonleaching Biocidal and Antibiofilm Activity

Polyurethanes from Hydrophobic Elastic Materials to Hydrogels with Potent Nonleaching Biocidal and Antibiofilm Activity

Rapid Assembly of Infection-Resistant Coatings: Screening and Identification of Antimicrobial Peptides Works in Cooperation with an Antifouling Background.

Bacterial adhesion and the succeeding biofilm formation onto surfaces are responsible for implant- and device-associated infections. Bifunctional coatings integrating both nonfouling components and antimicrobial peptides (AMPs) are a promising approach to develop potent antibiofilm coatings. However, the current approaches and chemistry for such coatings are time-consuming and dependent on substrates and involve a multistep process. Also, the information is limited on the influence of the coating structure or its components on the antibiofilm activity of such AMP-based coatings. Here, we report a new strategy to rapidly assemble a stable, potent, and substrate-independent AMP-based antibiofilm coating in a nonfouling background. The coating structure allowed for the screening of AMPs in a relevant nonfouling background to identify optimal peptide combinations that work in cooperation to generate potent antibiofilm activity. The structure of the coating was changed by altering the organization of the hydrophilic polymer chains within the coatings. The coatings were thoroughly characterized using various surface analytical techniques and correlated with the efficiency to prevent biofilm formation against diverse bacteria. The coating method that allowed the conjugation of AMPs without altering the steric protection ability of hydrophilic polymer structure results in a bifunctional surface coating with excellent antibiofilm activity. In contrast, the conjugation of AMPs directly to the hydrophilic polymer chains resulted in a surface with poor antibiofilm activity and increased adhesion of bacteria. Using this coating approach, we further established a new screening method and identified a set of potent surface-tethered AMPs with high activity. The success of this new peptide screening and coating method is demonstrated using a clinically relevant mouse infection model to prevent catheter-associated urinary tract infection (CAUTI).

Synthesis of silver-nisin nanoparticles with low cytotoxicity as antimicrobials against biofilm-forming pathogens

Wound infection is a serious threat to patients, in particular those with septic wound infections, which result in high mortality rates. Moreover, the treatment of wound infections with antimicrobial-resistant and/or biofilm-forming pathogens can be challenging. Nisin, a potent antimicrobial against Gram-positive bacterial pathogens, has been used in the food industry as a preservative for decades. Silver has been approved by the FDA as a topical antimicrobial. Here, we show that silver-nisin nanoparticles (Ag-nisin NP), with an average diameter of 60 nm, can be quickly synthesized with the assistance of a simple microwave. Ag-nisin NP act as bactericidal antibiotics against the tested pathogens. In contrast, resistance was observed in S. aureus and A. baumannii that were treated with silver nitrate alone. In addition, Ag-nisin NP showed potent antibiofilm activity against S. aureus, P. aeruginosa, A. baumannii, K. pneumoniae, and E. coli, which are pathogens occurring in wound infections. Notably, the synthesized Ag-nisin NP showed lower cytotoxicity than silver nitrate to human cells. This formulation provides an alternative and safe measurement for biofilm-infected wound control.

Alkylimidazolium ionic liquids for biofilm control: Experimental studies on controlling multispecies biofilms in natural waters

Biofilm associated problems and inherent resistance of biofilm-bacteria to antimicrobial agents drives the need for alternate agents with potent antibiofilm activities. Alkylimidazolium ionic liquids were reported as novel antimicrobial and antibiofilm agents for preventing single species biofilms. However, naturally occurring biofilms are multispecies in nature constituting diverse organisms and have high prevalence, significance in medical, industrial and ecological perspective. In this study, the effect of three alkylimidazolium ionic liquids ([CnMIM]+[X]−, n = 4, 12 and 16) were evaluated against formation of natural and multispecies biofilms in freshwater and seawater. In 96-well biofilm assays, [C4MIM][Cl] with –butyl alkyl group did not exert antibiofilm activity even at 500 µM. [C12MIM][I] with –dodecyl alkyl group showed antibiofilm activity at 32 and 250 µM, in natural freshwater and seawater, respectively. Among the tested ionic liquids, [C16MIM][Cl] with –hexadecyl group showed superior antibiofilm activity. Presence of [C16MIM][Cl] in freshwater and seawater, respectively, at 8 and 125 µM caused complete inhibition in biofilm formation. Among the tested compounds, only [C16MIM][Cl] showed biofilm dispersal activity on pre-formed biofilms. Biofilm dispersal was near complete at 125 and 250 µM for freshwater and seawater biofilms, respectively. Potent antimicrobial ionic liquid ([C16MIM][Cl]) was further evaluated for biofilm prevention under dynamic conditions in a laboratory scale recirculation system. Over a period of 12 d of operation, biofilm formation was retarded in the presence of 100 μM and 250 μM of [C16MIM][Cl], in freshwater and seawater, respectively. The results suggest that antimicrobial [C16MIM][Cl] may find potential application for preventing multispecies biofilms in cooling water systems.

Soybeans agroindustrial residues as Staphylococcus epidermidis and S. aureus biofilm inhibitors

The reuse of agroindustrial waste has been the subject of several studies since they present rich chemical composition and their disposal generates costs to industries and harmful potential to the environment. Compounds present in soybean residues may have a potential antibiofilm activity, a property still very little explored in this raw material. The seek for active compounds against biofilms, has been extremely important, since they represent a challenge in clinical and industrial environments. Thus, this study aimed to evaluate the potential antibiofilm and antimicrobial activities of extracts obtained from soybeans processing residues against Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. Antibacterial and antibiofilm activities of two crude extracts were evaluated using absorbance (620 nm), colony-forming units (CFU) counting, and the crystal violet method, respectively. The safety of these compounds was assessed using the alternative model Caenorhabditis elegans. The extract obtained from fragments of the grain and stalks (E1) had its chemical characterization investigated and was submitted fractionation by ultrafiltration. The proteomic and metabolomic analysis of an active fraction was performed using liquid chromatography and mass spectrometry. E1 (4 mg/mL) inhibited 75 % of the S. epidermidis biofilm formation with no inhibition of bacterial growth. Antibiofilm activity of E1 was lost when it was submitted to a heat treatment, while the enzymatic treatment with proteinase K led to a loss of 30 % in the activity of the extract, suggesting that the antibiofilm molecules may be of protein origin. When submitted to the ultrafiltration process, the antibiofilm activity was observed mainly when two fractions (fraction> 50 kDa (R50) and fraction <10 kDa (F10′)) were combined, suggesting that the biological activity is dependent on the combination of the active molecules. The metabolomic analysis of F10′ indicated the presence of flavonoids, lipids, peptides, organic compounds and nucleosides while in the proteomic analysis of R50 a total of 19 proteins were identified. The extract E1 and the active fraction (R50+F10′) showed low toxicity in C. elegans. This work shows that soybeans agroindustrial residues may be a potential source of molecules with activity against bacterial biofilms.