Antibody-conjugated and streptomycin-chitosan oligosaccharide-modified gold nanoshells for synergistic chemo-photothermal therapy of drug-resistant bacterial infection.

Despite the many advanced strategies that are available, rapid gene mutation in multidrug-resistant bacterial infections remains a major challenge. Combining new therapeutic strategies such as chemo-photothermal therapy (PTT) with high antibacterial efficiency against drug-resistant Listeria monocytogenes (LM) is urgently needed. Here, we report synergistic chemo-PTT against drug-resistant LM based on antibody-conjugated and streptomycin-chitosan oligosaccharide-modified gold nanoshells (anti-STR-CO-GNSs) as all-in-one nanotheranostic agents for the first time, which was used for accurate antibacterial applications. The anti-STR-CO-GNSs showed excellent photothermal conversion efficiency (31.97 %) and were responsive to near-infrared (NIR) and pH dual stimuli-triggered antibiotic release, resulting in outstanding chemo-photothermal effects against LM. In vitro chemo-photothermal effect of anti-STR-CO-GNSs with laser irradiation caused a greater antibacterial effect (1.37 %), resulting in more rapid killing of LM and prevention of LM regrowth. Most importantly, the mice receiving the anti-STR-CO-GNSs with laser irradiation specifically at the sites of LM infections healed almost completely, leaving only scars on the surface of the skin and resulting in superior inhibitory effects from combined chemo-PTT. Overall, our findings suggest that chemo-PTT using smart biocompatible anti-STR-CO-GNSs is a favorable potential alternative to combat the increasing threat of drug-resistant LM, which opens a new door for clinical anti-infection therapy in the future.

Retrospective analysis of the key molecules involved in the green synthesis of nanoparticles.

Emerging nanotechnology leads to success in synthesizing and applying nanoparticles (NPs) using the green-chemistry approach. NPs synthesized using naturally derived materials are a potential alternative to chemical and physical methods because they are simple, cost-effective, eco-friendly, and lower the possibility of hazardous residues being released into the environment. Furthermore, NPs synthesized using the green synthesis approach are stable and biocompatible. However, because natural extracts contain a diverse spectrum of bioactive components, it is difficult to pinpoint the specific component involved in NP formation. Furthermore, the bioactive component contained in the extract changes based on a number of environmental factors; therefore, several studies began with the synthesis of NPs using a pure compound isolated from diverse natural sources. Hence, the present review paper makes an effort to retrospectively analyze the key compounds of the extracts which are responsible for the synthesis of the NPs. The analysis was carried out based on the physicochemical characteristics and biological activities of NPs synthesized from either the extract or the pure compounds. These pure-compound-based NPs were studied for their antimicrobial, antibiofilm, anti-inflammatory, anticancer, and antioxidant properties. In addition, the present review also describes progress in the study of pure compound-based numerous biological activities and the underlying mechanisms of action.

Combination Therapy for Bacterial Pathogens: Naturally Derived Antimicrobial Drugs Combined with Ulva lactuca Extract.

BACKGROUND: With the growing incidence of microbial pathogenesis, several alternative strategies have been developed. The number of treatments using naturally (e.g., plants, algae, fungi, bacteria, and animals) derived compounds has increased. Importantly, marine-derived products have become a promising and effective approach to combat the antibiotic resistance properties developed by bacterial pathogens. Furthermore, augmenting the sub-inhibitory concentration of the naturally-derived antimicrobial compounds (e.g., hydroxycinnamic acids, terpenes, marine-derived polysaccharides, phenolic compounds) into the naturally derived extracts as a combination therapy to treat the bacterial infection has not been well studied. OBJECTIVE: The present study was aimed to prepare green algae Ulva lactuca extract and evaluate its antibacterial activity towards Gram-positive and Gram-negative human pathogenic bacteria. Also, revitalize the antibacterial efficiency of the naturally-derived antimicrobial drugs and conventional antibiotics by mixing their sub-MIC to the U. lactuca extracts. METHODS: Extraction was done using a different organic solvent, and its antibacterial activity was tested towards Gram-positive and Gram-negative pathogens. The minimum inhibitory concentration (MIC) of U. lactuca extracts has been determined towards pathogenic bacteria using the micro broth dilution method. The viable cell counting method was used to determine the minimum bactericidal concentration (MBC). The fractional inhibitory concentration (FIC) assay was utilized to examine the combinatorial impact of sub-MIC of two antibacterial drugs using the micro broth dilution method. The chemical components of the extract were analyzed by GC-MS analysis. RESULTS: Among all the extracts, n-hexane extract was found to show effective antibacterial activity towards tested pathogens with the lowest MIC and MBC value. Furthermore, the n-hexane extracts have also been used to enhance the efficacy of the naturally-derived (derived from plants and marine organisms) compounds and conventional antibiotics at their sub-inhibitory concentrations. Most of the tested antibiotics and natural drugs at their sub-MIC were found to exhibit synergistic and additive antibacterial activity towards the tested bacterial pathogens. CONCLUSIONS: The combining of U. lactuca n-hexane extracts with natural drugs resulted in synergistic and additive bactericidal effects on Gram-positive and Gram-negative human pathogenic bacteria. The present study shows a new alternative strategy to revitalize the antimicrobial activity of naturally derived compounds for treating human bacterial pathogens.

Effect of Zr doping on photoantioxidant and antibiofilm properties of CeO2 NPs fabricated using aqueous leaf extract of Pometia pinnata.

Synthesized cerium oxide nanoparticles (S-CeO2 NPs) and 1%, 5% and 10% zirconium doped CeO2 (Zr-doped CeO2) NPs were fabricated using aqueous leaf extract of Pometia pinnata. The synthesized NPs were characterized using standard techniques which confirmed successful synthesis of NPs with particle size ranging from 12 to 23 nm and band gap energy of 2.54-2.66 eV. Photoantioxidant activities showed enhanced activities under visible light irradiation in comparison to the dark condition in the dose-dependent study. Biofilm inhibition studies showed ~ 73% biofilm inhibition of Staphylococcus aureus at 512 µg/mL for S-CeO2, whereas 10% Zr-doped CeO2 NPs showed biofilm inhibition of 52.7%. The bactericidal tests showed killing properties at 1024 µg/mL of S-CeO2 NPs and at 512 µg/mL of 1% Zr-doped CeO2. Reduced bactericidal activities were observed for 5% and 10% Zr-doped CeO2. These studies showed that the fabricated NPs have both good photoantioxidant and antibacterial properties.

Phloroglucinol-Gold and -Zinc Oxide Nanoparticles: Antibiofilm and Antivirulence Activities towards Pseudomonasaeruginosa PAO1.

With the advancement of nanotechnology, several nanoparticles have been synthesized as antimicrobial agents by utilizing biologically derived materials. In most cases, the materials used for the synthesis of nanoparticles from natural sources are extracts. Natural extracts contain a wide range of bioactive components, making it difficult to pinpoint the exact component responsible for nanoparticle synthesis. Furthermore, the bioactive component present in the extract changes according to numerous environmental factors. As a result, the current work intended to synthesize gold (AuNPs) and zinc oxide (ZnONPs) nanoparticles using pure phloroglucinol (PG). The synthesized PG-AuNPs and PG-ZnONPs were characterized using a UV-Vis absorption spectrophotometer, FTIR, DLS, FE-TEM, zeta potential, EDS, and energy-dispersive X-ray diffraction. The characterized PG-AuNPs and PG-ZnONPs have been employed to combat the pathogenesis of Pseudomonas aeruginosa. P. aeruginosa is recognized as one of the most prevalent pathogens responsible for the common cause of nosocomial infection in humans. Antimicrobial resistance in P. aeruginosa has been linked to the development of recalcitrant phenotypic characteristics, such as biofilm, which has been identified as one of the major obstacles to antimicrobial therapy. Furthermore, P. aeruginosa generates various virulence factors that are a major cause of chronic infection. These PG-AuNPs and PG-ZnONPs significantly inhibit early stage biofilm and eradicate mature biofilm. Furthermore, these NPs reduce P. aeruginosa virulence factors such as pyoverdine, pyocyanin, protease, rhamnolipid, and hemolytic capabilities. In addition, these NPs significantly reduce P. aeruginosa swarming, swimming, and twitching motility. PG-AuNPs and PG-ZnONPs can be used as control agents for infections caused by the biofilm-forming human pathogenic bacterium P. aeruginosa.

Synergistic Antibacterial Activity of an Active Compound Derived from Sedum takesimense against Methicillin-Resistant Staphylococcus aureus and Its Clinical Isolates.

There are a growing number of reports of hospital-acquired infections caused by pathogenic bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA). Many plant products are now being used as a natural means of exploring antimicrobial agents against different types of human pathogenic bacteria. In this research, we sought to isolate and identify an active molecule from Sedum takesimense that has possible antibacterial activity against various clinical isolates of MRSA. NMR analysis revealed that the structure of the HPLC-purified compound was 1,2,4,6-tetra-O-galloyl-glucose. The minimum inhibitory concentration (MIC) of different extract fractions against numerous pathogenic bacteria was determined, and the actively purified compound has potent antibacterial activity against multidrug-resistant pathogenic bacteria, i.e., MRSA and its clinical isolates. In addition, the combination of the active compound and ß-lactam antibiotics (e.g., oxacillin) demonstrated synergistic action against MRSA, with a fractional inhibitory concentration (FIC) index of 0.281. The current research revealed an alternative approach to combating pathogenesis caused by multi-drug resistant bacteria using plant materials. Furthermore, using a combination approach in which the active plant-derived compound is combined with antibiotics has proved to be a successful way of destroying pathogens synergistically.

Green synthesis of CeO2 and Zr/Sn-dual doped CeO2 nanoparticles with photoantioxidant and antibiofilm activities.

Cerium oxide (CeO2) and 1%, 5% and 10% zirconium/tin-dual doped CeO2 nanoparticles (Zr/Sn-dual doped CeO2 NPs) were synthesized using an aqueous leaf extract of Pometia pinnata. By using UV-visible diffuse reflectance spectroscopy, the band gap energies of these materials were found to be in the range of ∼2.49 to 2.66 eV. The average crystallite sizes of the fluorite phase obtained from X-ray diffraction were between 7 and 16 nm. X-ray photoelectron spectroscopy (XPS) analysis further confirmed the synthesis of CeO2 and Sn-doped CeO2 NPs. Almost spherical shapes of the nanomaterials with an average particle size of 12-17 nm were determined using scanning electron microscopy and transmission electron microscopy studies. Photoantioxidant activities of the synthesized materials showed enhanced photoantioxidant response under visible light irradiation in comparison with those under dark conditions in both dose- and time-dependent manner. The CeO2 NPs exhibited a significant concentration-dependent antibiofilm activity against the Gram-positive bacteria Staphylococcus aureus (S. aureus) and Listeria monocytogenes (L. monocytogenes). Only the 10% Zr/Sn-dual doped-CeO2 NPs were found to inhibit S. aureus biofilm formation at higher concentrations. All Zr/Sn-dual doped CeO2 NPs exhibited a concentration-dependent biofilm inhibition of L. monocytogenes and also bactericidal activity towards S. aureus. These nanomaterials exhibited enhanced photoantioxidant activities and antibacterial properties, which make them suitable for various biological applications.

Bactericidal Activity of Sargassum aquifolium (Turner) C. Agardh against Gram-positive and Gram-negative Biofilm-forming Pathogenic Bacteria.

AIM: To study the bactericidal activity of crude ethanolic extract and fractionations obtained from Sargassum aquifolium (Turner) C. Agardh (brown algae) towards Gram-positive bacteria and Gram-negative biofilm-forming human pathogenic bacteria. BACKGROUND: The increasing emergence of antibiotic-resistant bacteria in the hospital and community settings has led to the discovery of alternative strategies. Marine organisms are considered as one of the potential sources of diverse bioactive molecules against several biological activities. Hence, the algae, especially the marine brown algae were selected to evaluate its antibacterial activities towards biofilm-forming human pathogenic bacteria. OBJECTIVE: To restrain the drug-resistant ability of pathogenic bacteria, we checked the extract of Sargassum aquifolium (Turner) C. Agardh (Phyophyceae) for the concerned bioactive compounds. METHODS: Antibacterial activity towards both Gram-positive and Gram-negative bacteria was evaluated using disk diffusion and broth microdilution assays. Furthermore, the active compound present in the extracts was also identified using Gas-Chromatography-Mass Spectroscopy (GC-MS). RESULTS: A total of 21 bioactive compounds were identified using GC-MS analysis with different chemical natures. The crude ethanolic extraction was fractionated sequentially according to the eluotropic series from less to extreme polar. The highest zone of inhibition was recorded for ethanolic extract on Listeria monocytogenes with a value of 38.00±0.17 mm and the lowest was 10.67±0.06 mm for ethyl acetate fraction on Pseudomonas aeruginosa. Ethyl acetate fractionate showed a higher effectivity than other fractionations. An MIC value of 256 µg/mL was recorded against Staphylococcus aureus and L. monocytogenes and 512 µg/mL against Escherichia coli and P. aeruginosa. Its ethanolic extract also showed synergism with oxytetracycline on S. aureus, L. monocytogenes, and E. coli. Furthermore, the same extracts also showed synergism with tetracycline on E. coli and with erythromycin on P. aeruginosa. CONCLUSION: The present study reports the antibacterial activity of the S. aquifolium (Turner) C. Agardh extracts against human pathogenic bacteria. Furthermore, it also predicts the synergistic activity of selected antibiotic combinations against both selected Gram-positive and Gram-negative pathogenic bacteria.

Thiol chitosan-wrapped gold nanoshells for near-infrared laser-induced photothermal destruction of antibiotic-resistant bacteria.

Developing new antibacterial nanomaterials and novel therapeutic strategies for the destruction of human pathogenic bacteria that cause infectious diseases is becoming more crucial, because infections caused by antibiotic-resistant bacteria are becoming more and more difficult to be effectively cured with commercially available antibiotics. In this study, we successfully developed new thiol chitosan-wrapped gold nanoshells (TC-AuNSs) as an antibacterial agent for the near-infrared (NIR) laser-triggered photothermal destruction of antibiotic-resistant pathogens, such as Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli), owing to their high water solubility, biocompatibility, strong NIR absorption, and outstanding photothermal properties. More interestingly, TC-AuNSs (115 µg/mL) were capable of completely destroying S. aureus, P. aeruginosa, and E.coli within 5 min of NIR laser irradiation, and no bacterial growth was detected on the tryptic soy agar (TSA) plate after 48 h of laser irradiation, indicating that TC-AuNSs along with laser irradiation are highly efficient and can kill bacteria quickly and prevent bacterial regrowth. We believe that TC-AuNSs deserve much more attention as an antibacterial agent, to be used in effectively combating pathogenic bacteria associated with public health problems and monitoring of environmental pollution for hygiene and safety.

Medicinal Plant Compounds for Combating the Multi-drug Resistant Pathogenic Bacteria: A Review.

BACKGROUND: Globally, people utilize plants as the main source of remedy to heal various ailments. Medicinal plants have been utilized to treat ailments since the invention of modern scientific systems of medicine. The common remedy of infectious diseases mainly depends on the inhibition capacity of compounds or killing potential. The issue may give a clue for the development of a novel antimicrobial agent. METHODS: Currently, microorganisms which are resistant towards antibiotics are probably a matter of serious concern for the overall well-being of health. At the moment, new therapeutic targets aside from the microorganism wall-based activities are in progress. For instance, the autoinducer molecules produced by the quorum sensing system are used to control antibiotic resistance and biofilm formation. RESULTS: This therapeutic target is well-studied worldwide, however, the scientific data are not updated and only current studies started to gain insight into its perspective as a target to struggle against infectious diseases. Microbial resistance against antimicrobial compounds is a topic of serious concern in recent time. CONCLUSION: Hence, this paper aims to confer a current overview of the novel compounds, quorum sensing, quorum quenching, biofilm formation in the development of antibiotic resistance and an update on their importance as a potential target for natural substances.

Recent Progress and Future Perspectives of Antibiofilm Drugs Immobilized on Nanomaterials.

BACKGROUND: A novel strategy has been adapted to combat the threat caused by biofilm forming-pathogenic bacteria in our environments. It involves the synthesis of antibiofilm compounds biologically (metabolites from animals, microbes and plants) and chemically. As a result of extensive research, a significant number of antimicrobial compounds and biofilm inhibitors have been isolated and characterized from different biological and chemical sources. However, lots of limitations such as poor delivery, water-insolubility, stability, expulsion by efflux pumps, and the development of acquired resistance due to long-term exposure have been associated with these compounds. METHODS: Conjugation or encapsulation of these antibiofilm drugs with different biocompatible, biodegradable, chemically and thermally stable nanomaterials results in enhanced efficiency of biofilm inhibition. RESULTS AND CONCLUSION: This review article evaluates the current impact of antibiofilm drugs including its delivery, efficiency of blocking cell attachment and molecular mechanisms of action that is conjugated or encapsulated with different types of biocompatible nanomaterials. It will lead to a better understanding of the antibiofilm drugs and their role in combating biofilms. It will also open new doors for the application of immobilized antibiofilm drugs.