Simple and Rapid Method of Microwell Array Fabrication for Drug Testing on 3D Cancer Spheroids.

Three-dimensional (3D) cell culture systems are becoming increasingly popular due to their ability to mimic the complex process of angiogenesis in cancer, providing more accurate and physiologically relevant data than traditional two-dimensional (2D) cell culture systems. Microwell systems are particularly useful in this context as they provide a microenvironment that more closely resembles the in vivo environment than traditional microwells. Poly(ethylene glycol) (PEG) microwells are particularly advantageous due to their bio-inertness and the ability to tailor their material characteristics depending on the PEG molecular weight. Although there are several methods available for microwell fabrication, most of them are time-consuming and expensive. The current study utilizes a low-cost laser etching technique on poly(methyl methacrylate) materials followed by molding with PDMS to produce microwells. The optimal conditions for making concave microwells are an engraving parameter speed of 600 mm/s, power of 20%, and a design diameter of the microwell of 0.4 mm. The artificial tumor achieved its full size after 7 days of cell growth in a microwell system, and the cells developed drugs through a live/dead assay test. The results of the drug testing revealed that the IC50 value of zerumbone-loaded liposomes in HepG2 was 4.53 pM, which is greater than the IC50 value of zerumbone. The HepG2 cancer sphere's 3D platform for medication testing revealed that zerumbone-loaded liposomes were very effective at high doses. These findings generally imply that zerumbone-loaded liposomes have the capacity to target the liver and maintain medication delivery.

Verticillium dahliae VdPBP1 Transcription Factor Is Required for Hyphal Growth, Virulence, and Microsclerotia Formation.

Verticillium dahliae, a fungal pathogen that affects more than 200 plant species, including tomatoes, requires specific proteins for its early steps in plant infection. One such crucial protein, VdPBP1, exhibits high expression in the presence of tomato roots. Its 313-amino acid C-terminal section restores adhesion in nonadhesive Saccharomyces cerevisiae strains. To uncover its role, we employed a combination of bioinformatics, genetics, and morphological analyses. Our findings underscore the importance of VdPBP1 in fungal growth and pathogenesis. Bioinformatic analysis revealed that the VdPBP1 gene consists of four exons and three introns, encoding a 952-codon reading frame. The protein features a 9aaTAD domain, LsmAD, and PAB1 DNA-binding sites, as well as potential nuclear localization and transmembrane helix signals. Notably, the deletion of a 1.1 kb fragment at the gene's third end impedes microsclerotia formation and reduces pathogenicity. Mutants exhibit reduced growth and slower aerial mycelial development compared to the wild type. The VdPBP1 deletion strain does not induce disease symptoms in tomato plants. Furthermore, VdPBP1 deletion correlates with downregulated microsclerotia formation-related genes, and promoter analysis reveals regulatory elements, including sites for Rfx1, Mig1, and Ste12 proteins. Understanding the regulation and target genes of VdPBP1 holds promise for managing Verticillium wilt disease and related fungal pathogens.

The Utilization of Machine Learning Algorithms for Assisting Physicians in the Diagnosis of Diabetes.

This paper investigates the use of machine learning algorithms to aid medical professionals in the detection and risk assessment of diabetes. The research employed a dataset gathered from individuals with type 2 diabetes in Ninh Binh, Vietnam. A variety of classification algorithms, including Decision Tree Classifier, Logistic Regression, SVC, Ada Boost Classifier, Gradient Boosting Classifier, Random Forest Classifier, and K Neighbors Classifier, were utilized to identify the most suitable algorithm for the dataset. The results of the present study indicate that the Random Forest Classifier algorithm yielded the most promising results, exhibiting a cross-validation score of 0.998 and an accuracy rate of 100%. To further evaluate the effectiveness of the selected model, it was subjected to a testing phase involving a new dataset comprising 67 patients that had not been previously seen. The performance of the algorithm on this dataset resulted in an accuracy rate of 94%, especially the study's notable finding is the algorithm's accurate prediction of the probability of patients developing diabetes, as indicated by the class 1 (diabetes) probabilities. This innovative approach offers a meticulous and quantifiable method for diabetes detection and risk evaluation, showcasing the potential of machine learning algorithms in assisting clinicians with diagnosis and management. By communicating the diabetes score and probability estimates to patients, the comprehension of their disease status can be enhanced. This information empowers patients to make informed decisions and motivates them to adopt healthier lifestyle habits, ultimately playing a crucial role in impeding disease progression. The study underscores the significance of leveraging machine learning in healthcare to optimize patient care and improve long-term health outcomes.

Fabrication of a Low-Cost Microfluidic Device for High-Throughput Drug Testing on Static and Dynamic Cancer Spheroid Culture Models.

Drug development is a complex and expensive process from new drug discovery to product approval. Most drug screening and testing rely on in vitro 2D cell culture models; however, they generally lack in vivo tissue microarchitecture and physiological functionality. Therefore, many researchers have used engineering methods, such as microfluidic devices, to culture 3D cells in dynamic conditions. In this study, a simple and low-cost microfluidic device was fabricated using Poly Methyl Methacrylate (PMMA), a widely available material, and the total cost of the completed device was USD 17.75. Dynamic and static cell culture examinations were applied to monitor the growth of 3D cells. α-MG-loaded GA liposomes were used as the drug to test cell viability in 3D cancer spheroids. Two cell culture conditions (i.e., static and dynamic) were also used in drug testing to simulate the effect of flow on drug cytotoxicity. Results from all assays showed that with the velocity of 0.005 mL/min, cell viability was significantly impaired to nearly 30% after 72 h in a dynamic culture. This device is expected to improve in vitro testing models, reduce and eliminate unsuitable compounds, and select more accurate combinations for in vivo testing.

Lower Extremity Nerve Conduction Abnormalities in Vietnamese Patients with Type 2 Diabetes: A Cross-Sectional Study on Peripheral Neuropathy and Its Correlation with Glycemic Control and Renal Function.

Peripheral neuropathy is a common complication of type 2 diabetes mellitus (T2DM) that results in nerve conduction abnormalities. This study aimed to investigate the parameters of nerve conduction in lower extremities among T2DM patients in Vietnam. A cross-sectional study was conducted on 61 T2DM patients aged 18 years and older, diagnosed according to the American Diabetes Association's criteria. Data on demographic characteristics, duration of diabetes, hypertension, dyslipidemia, neuropathy symptoms, and biochemical parameters were collected. Nerve conduction parameters were measured in the tibial and peroneal nerves, including peripheral motor potential time, response amplitude M, and motor conduction speed, as well as sensory conduction in the shallow nerve. The study found a high rate of peripheral neuropathy among T2DM patients in Vietnam, with decreased conduction rate, motor response amplitude, and nerve sensation. The incidence of nerve damage was highest in the right peroneal nerve and left peroneal nerve (86.7% for both), followed by the right tibial nerve and left tibial nerve (67.2% and 68.9%, respectively). No significant differences were found in the rate of nerve defects between different age groups, body mass index (BMI) groups, or groups with hypertension or dyslipidemia. However, a statistically significant association was found between the rate of clinical neurological abnormalities and the duration of diabetes (p < 0.05). Patients with poor glucose control and/or decreased renal function also had a higher incidence of nerve defects. The study highlights the high incidence of peripheral neuropathy among T2DM patients in Vietnam and the association between nerve conduction abnormalities and poor glucose control and/or decreased renal function. The findings underscore the importance of early diagnosis and management of neuropathy in T2DM patients to prevent serious complications.

Insight into the Speciation of Heavy Metals in the Contaminated Soil Incubated with Corn Cob-Derived Biochar and Apatite.

Soil heavy metal contamination is a severe issue. The detrimental impact of contaminated heavy metals on the ecosystem depends on the chemical form of heavy metals. Biochar produced at 400 °C (CB400) and 600 °C (CB600) from corn cob was applied to remediate Pb and Zn in contaminated soil. After a one month amendment with biochar (CB400 and CB600) and apatite (AP) with the ratio of 3%, 5%, 10%, and 3:3% and 5:5% of the weight of biochar and apatite, the untreated and treated soil were extracted using Tessier's sequence extraction procedure. The five chemical fractions of the Tessier procedure were the exchangeable fraction (F1), carbonate fraction (F2), Fe/Mn oxide fraction (F3), organic matter (F4), and residual fraction (F5). The concentration of heavy metals in the five chemical fractions was analyzed using inductively coupled plasma mass spectroscopy (ICP-MS). The results showed that the total concentration of Pb and Zn in the soil was 3023.70 ± 98.60 mg kg-1 and 2034.33 ± 35.41 mg kg-1, respectively. These figures were 15.12 and 6.78 times higher than the limit standard set by the United States Environmental Protection Agency (U.S. EPA 2010), indicating the high level of contamination of Pb and Zn in the studied soil. The treated soil's pH, OC, and EC increased significantly compared to the untreated soil (p > 0.05). The chemical fraction of Pb and Zn was in the descending sequence of F2 (67%) > F5 (13%) > F1 (10%) > F3 (9%) > F4 (1%) and F2~F3 (28%) > F5 (27%) > F1 (16%) > F4 (0.4%), respectively. The amendment of BC400, BC600, and apatite significantly reduced the exchangeable fraction of Pb and Zn and increased the other stable fractions including F3, F4, and F5, especially at the rate of 10% of biochar and a combination of 5:5% of biochar and apatite. The effects of CB400 and CB600 on the reduction in the exchangeable fraction of Pb and Zn were almost the same (p > 0.05). The results showed that CB400, CB600, and the mixture of these biochars with apatite applied at 5% or 10% (w/w) could immobilize lead and zinc in soil and reduce the threat to the surrounding environment. Therefore, biochar derived from corn cob and apatite could be promising materials for immobilizing heavy metals in multiple-contaminated soil.

Chemical Fractionations of Lead and Zinc in the Contaminated Soil Amended with the Blended Biochar/Apatite.

Heavy metal contamination in agricultural land is an alarming issue in Vietnam. It is necessary to develop suitable remediation methods for environmental and farming purposes. The present study investigated the effectiveness of using peanut shell-derived biochar to remediate the two heavy metals Zn and Pb in laboratory soil assays following Tessier's sequential extraction procedure. The concentration of heavy metals was analyzed using Inductively coupled plasma mass spectrometry (ICP-MS). This study also compared the effectiveness of the blend of biochar and apatite applied and the mere biochar amendment on the chemical fractions of Pb and Zn in the contaminated agricultural soil. Results have shown that the investigated soil was extremely polluted by Pb (3047.8 mg kg−1) and Zn (2034.3 mg kg−1). In addition, the pH, organic carbon, and electrical conductivity values of amended soil samples increased with the increase in the amendment's ratios. The distribution of heavy metals in soil samples was in the descending order of carbonate fraction (F2) > residue fraction (F5) > exchangeable fraction (F1) > Fe/Mn oxide fraction (F3) > organic fraction (F4) for Pb and F5 ≈ F2 > F1 > F3 > F4 for Zn. The peanut shell-derived biochar produced at 400 °C and 600 °C amended at a 10% ratio (PB4:10 and PB6:10) could significantly reduce the exchangeable fraction Zn from 424.82 mg kg−1 to 277.69 mg kg−1 and 302.89 mg kg−1, respectively, and Pb from 495.77 mg kg−1 to 234.55 mg kg−1 and 275.15 mg kg−1, respectively, and immobilize them in soil. Amending the biochar and apatite combination increased the soil pH, then produced a highly negative charge on the soil surface and facilitated Pb and Zn adsorption. This study shows that the amendment of biochar and biochar blended with apatite could stabilize Pb and Zn fractions, indicating the potential of these amendments to remediate Pb and Zn in contaminated soil.

Synthesis of glycyrrhetinic acid-modified liposomes to deliver Murrayafoline A for treatment of hepatocellular carcinoma.

Hepatocellular carcinoma is a common type of cancer associated with a high mortality rate. Among several bioactive compounds, Murrayafoline A (MuA) has been proved as a bio substance that exhibits great potentials in treating liver cancer. In order to overcome the high cytotoxicity and low solubility of MuA, a delivery system based on nanocarriers is necessary to deliver MuA towards the desired target. In the present study, 18ß-glycyrrhetinic acid (GA), which is known as a ligand for liver targeting, was used to construct the cholesterol-poly (ethylene glycol)-glycyrrhetinic acid (GA-PEG-Chol) conjugate and liposome for MuA administration. The compound was then examined for therapeutic efficacy and safety in HUVEC and HepG2 cells in 2D and 3D cell cultures. Results have shown that MuA-loaded liposomes had IC50 value of 2 µM in HepG2 and had the cytosolic absorption of 8.83 ± 0.97 ng/105 cells, while The IC50 value of MuA-loaded liposomes in HUVEC cell lines was 15 µM and the the cytosolic absorption was recorded as 3.62 ± 0.61 cells. The drug test on the 3D cancer sphere platform of the HepG2 cancer sphere showed that MuA-loaded GA liposomes had the highest efficacy at a concentration of 100 µg/mL. In short, these results suggest that MuA-loaded GA liposomes have the potential for maintenance drug delivery and liver targeting.

A low-cost, flexible extruder for liposomes synthesis and application for Murrayafoline A delivery for cancer treatment.

Liposomal encapsulation is a drug delivery strategy with many advantages, such as improved bioavailability, ability to carry large drug loads, as well as controllability and specificity towards various targeted diseased tissues. Currently, most preparation techniques require an additional extrusion or filtering step to obtain monodisperse liposomes with the size of less than 100 nm. In this study, a compact liposome extruder was designed at a cost of $4.00 and used to synthesize liposome suspensions with defined particle size and high homogeneity for Murrayafoline A (Mu-A) loading and release. The synthesized MuA-loaded liposomes displayed a biphasic drug release and remained stable under the storage condition of 4°C. They also significantly reduced the viability of HepG2 cells in the cancer spheroids by 25%. The low-cost, flexible liposome extruder would allow the researchers to study liposomes and their applications in a cost-effective manner.

Mixed biofilms of pathogenic Candida-bacteria: regulation mechanisms and treatment strategies.

Mixed-species biofilm is one of the most frequently recorded clinical problems. Mixed biofilms develop as a result of interactions between microorganisms of a single or multiple species (e.g. bacteria and fungi). Candida spp., particularly Candida albicans, are known to associate with various bacterial species to form a multi-species biofilm. Mixed biofilms of Candida spp. have been previously detected in vivo and on the surfaces of many biomedical instruments. Treating infectious diseases caused by mixed biofilms of Candida and bacterial species has been challenging due to their increased resistance to antimicrobial drugs. Here, we review and discuss the clinical significance of mixed Candida-bacteria biofilms as well as the signalling mechanisms involved in Candida-bacteria interactions. We also describe possible approaches for combating infections associated with mixed biofilms, such as the use of natural or synthetic drugs and combination therapy. The review presented here is expected to contribute to the advances in the biomedical field on the understanding of underlying interaction mechanisms of pathogens in mixed biofilm, and alternative approaches to treating the related infections.

Molecules involved in motility regulation in Escherichia coli cells: a review.

The initial colonization of the host organism by commensal, probiotic, and pathogenic Escherichia coli strains is an important step in the development of infections and biofilms. Sensing and colonization of host cell surfaces are governed by flagellar and fimbriae/pili appendages, respectively. Biofilm formation confers great advantages on pathogenic E. coli cells such as protection against the host immune system, antimicrobial agents, and several environmental stress factors. The transition from planktonic to sessile physiological states involves several signaling cascades and factors responsible for the regulation of flagellar motility in E. coli cells. These regulatory factors have thus become important targets to control pathogenicity. Hence, attenuation of flagellar motility is considered a potential therapy against pathogenic E. coli. The present review describes signaling pathways and proteins involved in direct or indirect regulation of flagellar motility. Furthermore, application strategies for antimotility natural or synthetic compounds are discussed also.

Treatment strategies targeting persister cell formation in bacterial pathogens.

Persister cells are transiently antibiotic-tolerant and dormant subpopulations that are produced to escape the effects of antibiotics within biofilms or planktonic cell populations. Persister cells are of high clinical importance due to their tolerance to antimicrobial agents and subsequent failure in antibiotic treatments. Understanding persister cell formation mechanisms is therefore highly important for developing effective therapeutic strategies against pathogenic bacterial persisters. Several anti-persister compounds have been previously identified via isolation from natural resources or chemical synthesis. Furthermore, a combination of these compounds with antibiotics or non-antibiotic drugs also allows action on multiple targets while reducing the administration frequency. Here, we present a comprehensive overview of the clinical importance and formation mechanisms of persister cells as well as the current treatment strategies against persister cell formations in chronic infections.

Alternative strategies for the application of aminoglycoside antibiotics against the biofilm-forming human pathogenic bacteria.

Aminoglycosides are one of the common classes of antibiotics that have been widely used for treating infections caused by pathogenic bacteria. The mechanism of bactericidal action by aminoglycosides is well-known, by which it terminates the cytoplasmic protein synthesis. However, the potentials of aminoglycosides become hindered when facing the evolution of bacterial resistance mechanisms. Among multiple resistance mechanisms displayed by bacteria against antibiotics, the formation of biofilm is the mechanism that provides a barrier for antibiotics to reach the cellular level. Bacteria present in the biofilm also get protection against the impact of host immune responses, harsh environmental conditions, and other antimicrobial treatments. Hence, with the multifaceted resistance developed by biofilm-forming pathogenic bacteria, antibiotics are therefore discontinued for further applications. However, the recent research developed several alternative strategies such as optimization of the active concentration, modification of the environmental conditions, modification of the chemical structure, combinatorial application with other active agents, and formulation with biocompatible carrier materials to revitalize and exploit the new potential of aminoglycosides. The present review article describes the above mentioned multiple approaches and possible mechanisms for the application of aminoglycosides to treat biofilm-associated infections.

Streptomycin mediated biofilm inhibition and suppression of virulence properties in Pseudomonas aeruginosa PAO1.

Pseudomonas aeruginosa is known as an opportunistic pathogen whose one of the antibiotic resistance mechanisms includes biofilm formation and virulence factor production. The present study showed that the sub-minimum inhibitory concentration (sub-MIC) of streptomycin inhibited the formation of biofilm and eradicated the established mature biofilm. Streptomycin at sub-MIC was also capable of inhibiting biofilm formation on the urinary catheters. In addition, the sub-MIC of streptomycin attenuated the bacterial virulence properties as confirmed by both phenotypic and gene expression studies. The optimal conditions for streptomycin to perform anti-biofilm and anti-virulence activities were proposed as alkaline TSB media (pH 7.9) at 35 °C. However, sub-MIC of streptomycin also exhibited a comparative anti-biofilm efficacy in LB media at similar pH level and temperature. Furthermore, this condition also improved the biofilm inhibition and eradication properties of streptomycin, tobramycin and tetracycline towards the biofilm formed by a clinical isolate of P. aeruginosa. Findings from the present study provide an important insight for further studies on the mechanisms of biofilm inhibition and dispersion of pre-existing biofilm by streptomycin as well as tobramycin and tetracycline under a specific culture environment.

Regulation and controlling the motility properties of Pseudomonas aeruginosa.

Chronic infections caused by Pseudomonas aeruginosa have been a major concern as their spread and mortality continue to be on the rise. These infections are majorly attributed to biofilm formation via sequential steps where motility plays an essential role in initial attachment of bacterial cells onto biotic and abiotic surfaces, thereby contributing to multi-drug resistance among pathogens. Therefore, attenuating motility properties can be considered as highly potential for controlling P. aeruginosa biofilm formation. This strategy has employed the use of various natural and chemically synthesized compounds. The present review article explained the importance and regulation of different types of motilities properties. Furthermore, it also covered several important alternative approaches using anti-motility agents which could be helpful for controlling P. aeruginosa biofilm-associated infections. Further studies are required for in-depth understandings about the mechanisms of motilities controlling of these molecules at molecular levels.

Chitosan and their derivatives: Antibiofilm drugs against pathogenic bacteria.

Biofilm formed by several pathogenic bacteria results in the development of resistance against antimicrobial compounds. The polymeric materials present in the biofilm architecture hinder the entry of antimicrobial compounds through the surface of bacterial cells which are embedded as well as enclosed beneath the biofilm matrix. Recent and past studies explored the alternative approaches to inhibit the formation of biofilm by different agents isolated from plants, animals, and microbes. Among these agents, chitosan and its derivatives have got more attention due to their properties such as biodegradability, biocompatibility, non-allergenic and non-toxicity. Recent researches have focused on employing chitosan and its derivatives as effective agents to inhibit biofilm formation and attenuate virulence properties by various pathogenic bacteria. Such antibiofilm activity of chitosan and its derivatives can be further enhanced by conjugation with a wide range of bioactive compounds. The present review describes the antibiofilm properties of chitosan and its derivatives against the pathogenic bacteria. This review also summarizes the mechanisms of biofilm inhibition exhibited by these molecules. The knowledge of the antibiofilm activities of chitosan and its derivatives as well as their underlying mechanisms provides essential insights for widening their applications in the future.

Synthesis and characterization of chitosan oligosaccharide-capped gold nanoparticles as an effective antibiofilm drug against the Pseudomonas aeruginosa PAO1.

The infection caused by Pseudomonas aeruginosa is a serious concern in human health. The bacterium is an opportunistic pathogen which has been reported to cause nosocomial and chronic infections through biofilm formation and synthesis of several toxins and virulence factors. Furthermore, the formation of biofilm by P. aeruginosa is known as one of the resistance mechanisms against conventional antibiotics. Natural compounds from marine resources have become one of the simple, cost-effective, biocompatible and non-toxicity for treating P. aeruginosa biofilm-related infections. Furthermore, hybrid formulation with nanomaterials such as nanoparticles becomes an effective alternative strategy to minimize the drug toxicity problem and cytotoxicity properties. For this reason, the present study has employed chitosan oligosaccharide for the synthesis of chitosan oligosaccharide-capped gold nanoparticles (COS-AuNPs). The synthesized COS-AuNPs were then characterized by using UV-Visible spectroscopy, Dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), Field emission transmission electron microscopy (FE-TEM), and Energy dispersive X-ray diffraction (EDX). The synthesized COS-AuNPs were applied for inhibiting P. aeruginosa biofilm formation. Results have shown that COS-AuNPs exhibited inhibition to biofilm as well as eradication to pre-existing mature biofilm. Simultaneously, COS-AuNPs were also able to reduce bacterial hemolysis and different virulence factors produced by P. aeruginosa. Overall, the present study concluded that the hybrid nanoformulation such as COS-AuNPs could act as a potential agent to exhibit inhibitory properties against the P. aeruginosa pathogenesis arisen from biofilm formation.

Biofilm inhibition, modulation of virulence and motility properties by FeOOH nanoparticle in Pseudomonas aeruginosa.

Biofilm formation is one of the resistance mechanisms of Pseudomonas aeruginosa against antimicrobial compounds. Biofilm formation also characterizes for the infection and pathogenesis of P. aeruginosa, along with production of various virulence factors. With recent development of nanotechnology, the present study aims to employ the synthetic iron nanoparticle (FeOOH-NP) as an active agent to inhibit the formation of P. aeruginosa biofilm. The FeOOH-NP was synthesized and characterized with rod shape and average size of 40 nm. Inhibition of biofilm formation by the FeOOH-NP is in a concentration-dependent manner, with inhibition of biofilm formation increased as the FeOOH-NP concentration increased. Microscopic observations also confirmed the disruption of the biofilm architecture in the presence of the FeOOH-NP. In addition, the presence of the FeOOH-NP was also found to modulate bacterial motility as well as some other important virulence factors produced simultaneously with biofilm formation. These findings provide insights to anti-biofilm effect of a new iron NP, contributing to the search for an effective agent to combat P. aeruginosa infections resulted from biofilm formation.

Fucoidan-Stabilized Gold Nanoparticle-Mediated Biofilm Inhibition, Attenuation of Virulence and Motility Properties in Pseudomonas aeruginosa PAO1.

The emergence of antibiotic resistance in Pseudomonas aeruginosa due to biofilm formation has transformed this opportunistic pathogen into a life-threatening one. Biosynthesized nanoparticles are increasingly being recognized as an effective anti-biofilm strategy to counter P. aeruginosa biofilms. In the present study, gold nanoparticles (AuNPs) were biologically synthesized and stabilized using fucoidan, which is an active compound sourced from brown seaweed. Biosynthesized fucoidan-stabilized AuNPs (F-AuNPs) were subjected to characterization using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), field emission transmission electron microscopy (FE-TEM), dynamic light scattering (DLS), and energy dispersive X-ray diffraction (EDX). The biosynthesized F-AuNPs were then evaluated for their inhibitory effects on P. aeruginosa bacterial growth, biofilm formation, virulence factor production, and bacterial motility. Overall, the activities of F-AuNPs towards P. aeruginosa were varied depending on their concentration. At minimum inhibitory concentration (MIC) (512 µg/mL) and at concentrations above MIC, F-AuNPs exerted antibacterial activity. In contrast, the sub-inhibitory concentration (sub-MIC) levels of F-AuNPs inhibited biofilm formation without affecting bacterial growth, and eradicated matured biofilm. The minimum biofilm inhibition concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were identified as 128 µg/mL. Furthermore, sub-MICs of F-AuNPs also attenuated the production of several important virulence factors and impaired bacterial swarming, swimming, and twitching motilities. Findings from the present study provide important insights into the potential of F-AuNPs as an effective new drug for controlling P. aeruginosa-biofilm-related infections.

Antibiofilm and antivirulence properties of chitosan-polypyrrole nanocomposites to Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic human pathogen which exhibits its property of pathogenesis due to several factors, including the formation of biofilm and production of several virulence factors. Development of resistance properties against antibiotics leads to the discovery of certain alternative strategies to combat its pathogenesis. In the present study, a highly stable, biocompatible and water soluble nanocomposites (NCs) are synthesized from chitosan (CS) and the polypyrrole (PPy). The resultant chitosan-polypyrrole nanocomposites (CS-PPy NCs) inhibit the establishment of biofilm and also eradicate the preformed matured biofilm formed by P. aeruginosa. CS-PPy NCs inhibit the hemolytic and protease activities of P. aeruginosa. The NCs significantly reduce the production of many virulence factors such as pyocyanin, pyroverdine and rhamnolipid. CS-PPy NCs also suppress the bacterial motility such as swimming and swarming. The present study showed that highly stable CS-PPy NCs act as a potent antibiofilm and antivirulence drug for the treatment of P. aeruginosa infection.