Combination drug therapy by herbal nanomedicine prevent multidrug resistance protein 1: promote apoptosis in Lung Carcinoma.

Given the numerous adverse effects of lung cancer treatment, more research on non-toxic medications is urgently needed. Curcumin (CUR) and berberine (BBR) combat drug resistance by controlling the expression of multidrug resistant pump (MDR1). Fascinatingly, combining these medications increases the effectiveness of preventing lung cancer. Their low solubility and poor stability, however, restrict their therapeutic efficacy. Because of the improved bioavailability and increased encapsulation effectiveness of water-insoluble medicines, surfactant-based nanovesicles have recently received a great deal of attention. The current study sought to elucidate the Combination drug therapy by herbal nanomedicine prevent multidrug resistance protein 1: promote apoptosis in Lung Carcinoma. The impact of several tween (20, 60, and 80) types with varied hydrophobic tails on BBR/CUR-TNV was evaluated. Additionally, the MDR1 activity and apoptosis rate of the BBR/CUR-TNV combination therapy were assessed. The encapsulation effectiveness of TNV was affected by the type of tween. With the TNV made from tween 60, cholesterol, and PEG (47.5: 47.5:5), more encapsulation effectiveness was attained. By combining CUR with BBR, especially when given in TNV, apoptosis increased. Additionally, when CUR and BBR were administered in combination, they significantly reduced the risk of MDR1 development. The current work suggests that the delivery of berberine and curcumin as a combination medication therapy via tween-based nanovesicles may be a potential lung cancer treatment.

Process optimization for green synthesis of silver nanoparticles using Rubus discolor leaves extract and its biological activities against multi-drug resistant bacteria and cancer cells.

Multi-drug resistant (MDR) bacteria are considered a serious public health threat. Also, increasing rate of resistance to anticancer drugs, as well as their toxicity, is another point of concern. Therefore, the new antibacterial and anticancer agents are always needed. The synthesizing silver nanoparticles (AgNPs) using medicinal plants, is an effective approach for developing novel antibacterial and anticancer agents. Rubus discolor, a native species of the Caucasus region, produces leaves that are typically discarded as a by-product of raspberry production. The present study has focused on optimizing the green synthesis of AgNPs using R. discolor leaves extract through response surface methodology. The optimal values for AgNPs synthesis were an AgNO3 concentration of 7.11 mM, a time of 17.83 h, a temperature of 56.51 °C, and an extract percentage of 29.22. The production of AgNPs was confirmed using UV-visible spectroscopy (λmax at 456.01 nm). TEM analysis revealed well-dispersed AgNPs (an average size of 37 nm). The XRD analysis confirmed the crystalline structure. The EDX detected a strong peak at 3 keV corresponded to Ag. The zeta potential value (- 44.2 mV) indicated the stability of nanoparticles. FT-IR spectra showed the presence of various functional groups from plant compounds, which play an important role in the capping and bio-reduction processes. The AgNPs revealed impressive antibacterial activities against MDR Escherichia coli and Pseudomonas aeruginosa (MIC ranging from 0.93 to 3.75 mg ml-1). The phytochemical analysis indicated the presence of phenolics, tannins, and flavonoids on the surface of AgNPs. They also showed significant cytotoxic effects on A431, MCF-7, and HepG2 cells (IC50 values ranging from 11 to 49.1 µg ml-l).

In-depth analysis of the treatment effect and synergistic mechanism of TanReQing injection on clinical multi-drug resistant Pseudomonas aeruginosa.

Antibiotic resistance is a recognized and concerning public health issue. Gram-negative bacilli, such as Pseudomonas aeruginosa (P. aeruginosa), are notorious for their rapid development of drug resistance, leading to treatment failures. TanReQing injection (TRQ) was chosen to explore its pharmacological mechanisms against clinical multidrug-resistant P. aeruginosa (MDR-PA), given its antibacterial and anti-inflammatory properties. We revealed the expression of proteins and genes in P. aeruginosa after co-culture with TRQ. This study developed an assessment method to evaluate clinical resistance of P. aeruginosa using MALDI-TOF MS identification and Biotyper database searching techniques. Additionally, it combined MIC determination to investigate changes in MDR-PA treated by TRQ. TRQ effectively reduced the MICs of ceftazidime and cefoperazone and enhanced the confidence scores of MDR-PA as identified by mass spectrometry. Using this evaluation method, the fingerprints of standard P. aeruginosa and MDR-PA were compared, and the characteristic peptide sequence (Seq-PA No. 1) associated with flagellum was found. The phenotypic experiments were conducted to confirm the effect of TRQ on the motility and adhesion of P. aeruginosa. A combination of co-immunoprecipitation and proteome analysis was employed, and 16 proteins were significantly differentially expressed and identified as potential candidates for investigating the mechanism of inhibiting resistance in P. aeruginosa treated by TRQ. The candidates were verified by quantitative real-time PCR analysis, and TRQ may affect these core proteins (MexA, MexB, OprM, OprF, OTCase, IDH, and ASL) that influence resistance of P. aeruginosa. The combination of multiple methods helps elucidate the synergistic mechanism of TRQ in overcoming resistance of P. aeruginosa.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen closely associated with various life-threatening acute and chronic infections. The presence of antimicrobial resistance and multidrug resistance in P. aeruginosa infections significantly complicates antibiotic treatment. The expression of ß-lactamase, efflux systems such as MexAB-OprM, and outer membrane permeability are considered to have the greatest impact on the sensitivity of P. aeruginosa. The study used a method to assess the clinical resistance of P. aeruginosa using matrix-assisted laser desorption ionization time of flight mass spectrometry identification and Biotyper database search techniques. TanReQing injection (TRQ) effectively reduced the MICs of ceftazidime and cefoperazone in multidrug-resistant P. aeruginosa (MDR-PA) and improved the confidence scores for co-cultured MDR-PA. The study found a characteristic peptide sequence for distinguishing whether P. aeruginosa is resistant. Through co-immunoprecipitation and proteome analysis, we explored the mechanism of TRQ overcoming resistance of P. aeruginosa.

Supramolecular Assembly Based on Calix(4)arene and Aggregation-Induced Emission Photosensitizer for Phototherapy of Drug-Resistant Bacteria and Skin Flap Transplantation.

Photodynamic therapy as a burgeoning and non-invasive theranostic technique has drawn great attention in the field of antibacterial treatment but often encounters undesired phototoxicity of photosensitizers during systemic circulation. Herein, a supramolecular substitution strategy is proposed for phototherapy of drug-resistant bacteria and skin flap repair by using macrocyclic p-sulfonatocalix(4)arene (SC4A) as a host, and two cationic aggregation-induced emission luminogens (AIEgens), namely TPE-QAS and TPE-2QAS, bearing quaternary ammonium group(s) as guests. Through host-guest assembly, the obtained complex exhibits obvious blue fluorescence in the solution due to the restriction of free motion of AIEgens and drastically inhibits efficient type I ROS generation. Then, upon the addition of another guest 4,4'-benzidine dihydrochloride, TPE-QAS can be competitively replaced from the cavity of SC4A to restore its pristine ROS efficiency and photoactivity in aqueous solution. The dissociative TPE-QAS shows a high bacterial binding ability with an efficient treatment for methicillin-resistant Staphylococcus aureus (MRSA) in dark and light irradiation. Meanwhile, it also exhibits an improved survival rate for MRSA-infected skin flap transplantation and largely accelerates the healing process. Thus, such cascaded host-guest assembly is an ideal platform for phototheranostics research.

Second-line antituberculosis drug exposure thresholds predictive of adverse events in multidrug-resistant tuberculosis treatment.

OBJECTIVES: This study aimed to investigate the association between drug exposure and adverse events (AEs) during the standardized multidrug-resistant tuberculosis (MDR-TB) treatment, as well as to identify predictive drug exposure thresholds. METHODS: We conducted a prospective, observational multicenter study among participants receiving standardized MDR-TB treatment between 2016 and 2019 in China. AEs were monitored throughout the treatment and their relationships to drug exposure (e.g., the area under the drug concentration-time curve from 0 to 24 h, AUC0-24 h) were analyzed. The thresholds of pharmacokinetic predictors of observed AEs were identified by boosted classification and regression tree (CART) and further evaluated by external validation. RESULTS: Of 197 study participants, 124 (62.9%) had at least one AE, and 15 (7.6%) experienced serious AEs. The association between drug exposure and AEs was observed including bedaquiline, its metabolite M2, moxifloxacin and QTcF prolongation (QTcF >450 ms), linezolid and mitochondrial toxicity, cycloserine and psychiatric AEs. The CART-derived thresholds of AUC0-24 h predictive of the respective AEs were 3.2 mg·h/l (bedaquiline M2); 49.3 mg·h/l (moxifloxacin); 119.3 mg·h/l (linezolid); 718.7 mg·h/l (cycloserine). CONCLUSIONS: This study demonstrated the drug exposure thresholds predictive of AEs for key drugs against MDR-TB treatment. Using the derived thresholds will provide the knowledge base for further randomized clinical trials of dose adjustment to minimize the risk of AEs.

Botanical Extracts and Compounds of Castanea Plants and Methods of Use: US20190125818A1 - The United States Patent Evaluation.

BACKGROUND: Bacterial infections are increasingly difficult to combat, which makes them a threat to public health on a global level. Staphylococcus aureus is considered one of the main causes of infections in hospitals, as it has a variety of virulence factors, as well as is able to produce bacterial biofilms, which, consequently, bring numerous damages to public health as a result of increased resistance to conventional antibiotics and a longer hospital stay. Therefore, the use of compounds extracted from medicinal plants is a potential pharmaceutically acceptable target, as they do not have toxicity and the potential to disrupt biofilms produced by Staphylococcus aureus already evidenced, thus revealing their relevance to our study. OBJECTIVE: The objective of this work was to perform a critical analysis of a patent with natural extracts against bacterial biofilms found in the United States Patent and Trademark Office (USPTO) database, to map the possible bioactive compounds that may serve as potential future antimicrobial drugs. METHODS: A technological survey was carried out to verify existing patents using natural extracts with anti-biofilm potential. For this, it was searched with the keywords: Botanical extracts AND biofilms; which were performed in the United States Patent and Trademark Office (USPTO) database. Thus, the selected patent used a non-aqueous extract partitioned and vacuum-contracted, subsequently lyophilized for assays with antimicrobial potential. Because of this, a patent was analyzed regarding its chemistry, and biological activity, followed by a critical analysis of the technology proposed in the invention. RESULTS: When using the keywords Botanical extracts AND biofilms in the USPTO, it was possible to find twenty-two inventions; however, only four patents in the USPTO were in agreement with the proposal of the natural extract having antimicrobial activity and an anti-biofilm potential, of which two belonged to the same applicant with similar proposals. The key point of this invention was to enable the compounds of the Castanea sativa plant and its methods of obtaining the extract to present a significant antimicrobial action associated or not with antibiotics, promoting the development of new therapies against bacterial infections capable of disrupting biofilms. The invention developed a methodology for extracting Castanea sativa, in which pentacyclic triterpene compounds were found mostly in its leaves. Whereas for the extraction, the crude methanol extracts called extracts 224 from the ground leaves were made by maceration, filtered, combined, concentrated under pressure in rotary evaporators, and lyophilized. After that, they were resuspended in water and partitioned in succession with hexane, ethyl acetate, and butanol. The most active refined partition was the 224C extract with the solvent ethyl acetate, which was subjected to further fractionation using silica column chromatography. Resulting in the most refined extract, which was 224C-F2, capable of acting directly on the quorum sensing of bacteria, mainly Staphylococcus aureus, blocking the translation of RNAIII, including a series of exotoxins. Regarding the antimicrobial capacity against Staphylococcus aureus, it presented Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of 1.56 µg/mL-1 and > 100 µg/mL -1, respectively. CONCLUSION: Given the analyzed patent, it was possible to verify the importance of alternatives to reduce the impact of bacterial biofilms, which causes damage to industries in general and to health. From this, the invention analyzed has a promising proposal with antimicrobial potential focusing on the great impact of bacterial biofilms. Therefore, natural extracts with antibiofilmic potential can help to minimize the economic losses caused to health due to these multidrug-resistant microorganisms with different virulence mechanisms.

Antimicrobial efficacy of aloe-emodin mediated photodynamic therapy against antibiotic-resistant Pseudomonas aeruginosa in vitro.

Multidrug-resistant Pseudomonas aeruginosa is a common pathogen that causes topical infections following burn injuries. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising approach for treating antibiotic-resistant bacterial infections. The objective of this study was to evaluate the aPDT efficacy of aloe-emodin (AE), which is a photosensitizer extracted from traditional Chinese herbs, on antibiotic-sensitive and antibiotic-resistant P. aeruginosa in vitro. In this study, we confirmed the effectiveness of AE-mediated aPDT against both standard and MDR P. aeruginosa, explored the effects of irradiation time and AE concentration on bacterial survival in AE-mediated aPDT, and observed the structural damage of P. aeruginosa by using transmission electron microscope. Our results showed that neither AE nor light irradiation alone caused cytotoxic effects on P. aeruginosa. However, AE-mediated aPDT effectively inactivated both antibiotic-sensitive and antibiotic-resistant P. aeruginosa. The transmission electron microscope investigation showed that aPDT mediated by AE primarily caused damage to the cytoplasm and cell membrane. Our findings suggest that AE is a photosensitizer in the aPDT of MDR P. aeruginosa-caused topical infections following burn injuries. Future investigations will concentrate on the safety and efficacy of AE-mediated aPDT in animal models and clinical trials.

Interaction of zincite, alpha-terpineol, geranyl acetate, linalool, myrcenol, terpinolene, and thymol with virulence factors of Escherichia coli, Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Staphylococcus aureus.

BACKGROUND: Based on gas chromatography - mass spectrometry (GC-MS) results of a previous study, six metabolites including alpha-terpineol, geranyl acetate, linalool, myrcenol, terpinolene, and thymol showed significantly higher amounts relative to other metabolites. METHODS: A continuation of the previous study, the interaction of these metabolites with the main virulence factors of P. aeruginosa (pseudomonas elastase and exotoxin A), Staphylococcus aureus (alpha-hemolysin and protein 2a), Mycobacterium tuberculosis (ESX-secreted protein B and the serine/threonine protein kinase), and Escherichia coli (heat-labile enterotoxin and Shiga toxin) were evaluated by molecular docking study and molecular simulation. RESULTS: In the case of Shiga toxin, higher and lower binding affinities were related to alpha-terpinolene and zincite with values of -5.8 and -2.6 kcal/mol, respectively. For alpha-hemolysin, terpinolene and alpha-terpinolene demonstrated higher binding affinities with similar energies of -5.9 kcal/mol. Thymol and geranyl acetate showed lower binding energy of -5.7 kcal/mol toward protein 2a. Furthermore, thymol had a higher binding affinity toward heat-labile enterotoxin and ESX-secreted protein B with values of -5.9 and -6.1 kcal/mol, respectively. CONCLUSIONS: It is concluded that the availability of secondary metabolites of A. haussknechtii surrounding zinc oxide (ZnO) NPs can hinder P. aeruginosa by inactivating Pseudomonas elastase and exotoxin.

A descriptive study on isoniazid resistance-associated mutations, clustering and treatment outcomes of drug-resistant tuberculosis in a high burden country.

PURPOSE: To describe katG and inhA mutations, clinical characteristics, treatment outcomes and clustering of drug-resistant tuberculosis (TB) in the State of São Paulo, southeast Brazil. METHODS: Mycobacterium tuberculosis isolates from patients diagnosed with drug-resistant TB were screened for mutations in katG and inhA genes by line probe assay and Sanger sequencing, and typed by IS6110-restriction fragment-length polymorphism for clustering assessment. Clinical, epidemiological and demographic data were obtained from surveillance information systems for TB. RESULTS: Among the 298 isolates studied, 127 (42.6%) were isoniazid-monoresistant, 36 (12.1%) polydrug-resistant, 93 (31.2%) MDR, 16 (5.4%) pre-extensively drug-resistant (pre-XDR), 9 (3%) extensively drug-resistant (XDR) and 17 (5.7%) susceptible after isoniazid retesting. The frequency of katG 315 mutations alone was higher in MDR isolates, while inhA promoter mutations alone were more common in isoniazid-monoresistant isolates. Twenty-six isolates phenotypically resistant to isoniazid had no mutations either in katG or inhA genes. The isolates with inhA mutations were found more frequently in clusters (75%) when compared to the isolates with katG 315 mutations (59.8%, p = 0.04). In our population, being 35-64 years old, presenting MDR-, pre-XDR- or XDR-TB and being a retreatment case were associated with unfavourable TB treatment outcomes. CONCLUSION: We found that katG and inhA mutations were not equally distributed between isoniazid-monoresistant and MDR isolates. In our population, clustering was higher for isolates with inhA mutations. Finally, unfavourable TB outcomes were associated with specific factors.

Optimization of sequence and chiral content enhances therapeutic potential of tilapia piscidin peptides.

Because antimicrobial peptides (AMPs) often exhibit broad-spectrum bactericidal potency, we sought to develop peptide-based antimicrobials for potential clinical use against drug-resistant pathogens. To accomplish this goal, we first optimized the amino acid sequence of a broad-spectrum AMP known as Tilapia Piscidin 4 (TP4). Then, we used the optimized sequence to create a pair of heterochiral variants (TP4-α and TP4-ß) with different percentages of D-enantiomers, as poly-L peptides often exhibit poor pharmacokinetic profiles. The conformations of the peptide pair exhibited inverted chirality according to CD and NMR spectroscopic analyses. Both heterochiral peptides displayed enhanced stability and low hemolysis activities. Irrespective of their different d-enantiomer contents, both heterochiral peptides exhibited bactericidal activities in the presence of human serum or physiological enzymes. However, the peptide with higher d-amino acid content (TP4-ß) caused better bacterial clearance when tested in mice infected with NDM-1 K. pneumoniae. In addition, we observed a relatively higher hydrogen bonding affinity in a simulation of the interaction between TP4-ß and a model bacterial membrane. In sum, our results demonstrate that the current design strategy may be applicable for development of new molecules with enhanced stability and in vivo antimicrobial activity.

Antimicrobial Cyclic Dipeptides from Japanese Quail (Coturnix japonica) Eggs Supplemented with Probiotic Lactobacillus plantarum.

Fifteen cyclic dipeptides (CDPs) containing proline, one cyclo(Phe-Ala) without proline, and a non-peptidyl DL-3-phenyllactic acid were previously identified in the culture filtrates of Lactobacillus plantarum LBP-K10, an isolate from kimchi. In this study, we used Japanese quail (Coturnix japonica) eggs to examine the effects of probiotic supplementation on the antimicrobial CDPs extracted from quail eggs (QE). Eggshell-free QE were obtained from two distinct groups of quails. The first group (K10N) comprised eggs from unsupplemented quails. The second group (K10S) comprised eggs from quails supplemented with Lb. plantarum LBP-K10. The QE samples were extracted using methylene chloride through a liquid-liquid extraction process. The resulting extract was fractionated into 16 parts using semi-preparative high-performance liquid chromatography. Two fractions, Q6 and Q9, were isolated from K10S and identified as cis-cyclo(L-Ser-L-Pro) and cis-cyclo(L-Leu-L-Pro). The Q9 fraction, containing cis-cyclo(L-Leu-L-Pro), has shown significant inhibitory properties against the proliferation of highly pathogenic multidrug-resistant bacteria, as well as human-specific and phytopathogenic fungi. Some of the ten combinations between the remaining fourteen unidentified fractions and two fractions, Q6 and Q9, containing cis-cyclo(L-Ser-L-Pro) and cis-cyclo(L-Leu-L-Pro) respectively, demonstrated a significant increase in activity against multidrug-resistant bacteria only when combined with Q9. The activity was 7.17 times higher compared to a single cis-cyclo(L-Leu-L-Pro). This study presents new findings on the efficacy of proline-containing CDPs in avian eggs. These CDPs provide antimicrobial properties when specific probiotics are supplemented.

Green Synthesis of Chitosan-Capped Gold Nanoparticles Using Salvia officinalis Extract: Biochemical Characterization and Antimicrobial and Cytotoxic Activities.

Increasing antimicrobial resistance to the action of existing antibiotics has prompted researchers to identify new natural molecules with antimicrobial potential. In this study, a green system was developed for biosynthesizing gold nanoparticles (BAuNPs) using sage (Salvia officinalis L.) leaf extract bioconjugated with non-toxic, eco-friendly, and biodegradable chitosan, forming chitosan/gold bioconjugates (Chi/BAuNPs). Characterization of the BAuNPs and Chi/BAuNPs conjugates takes place using transmission electron microscopy (TEM), X-ray spectra, Fourier transform infrared (FT-IR) spectroscopy, and zeta potential (Z-potential). The chemical composition of S. officinalis extract was evaluated via gas chromatography/mass spectrometry (GC/MS). This study evaluated the antioxidant and antimicrobial activities of human pathogenic multidrug-resistant (MDR) and multisensitive (MS) bacterial isolates using the agar diffusion method. Chi/BAuNPs showed inhibition of the MDR strains more effectively than BAuNPs alone as compared with a positive standard antibiotic. The cytotoxicity assay revealed that the human breast adenocarcinoma cancer cells (MCF7) were more sensitive toward the toxicity of 5-Fu + BAuNPs and 5-Fu + Chi/BAuNPs composites compared to non-malignant human fibroblast cells (HFs). The study shows that BAuNPs and Chi/BAuNPs, combined with 5-FU NPs, can effectively treat cancer at concentrations where the free chemical drug (5-Fu) is ineffective, with a noted reduction in the required dosage for noticeable antitumor action.

Potentiation and Mechanism of Berberine as an Antibiotic Adjuvant Against Multidrug-Resistant Bacteria.

The growing global apprehension towards multi-drug resistant (MDR) bacteria necessitates the development of innovative strategies to combat these infections. Berberine (BER), an isoquinoline quaternary alkaloid derived from various medicinal plants, has surfaced as a promising antibiotic adjuvant due to its ability to enhance the effectiveness of conventional antibiotics against drug-resistant bacterial strains. Here, we overview the augmenting properties and mechanisms of BER as an adjunctive antibiotic against MDR bacteria. BER has been observed to exhibit synergistic effects when co-administered with a range of antibiotics, including ß-lactams, quinolones, aminoglycosides, tetracyclines, macrolides, lincosamides and fusidic acid. The adjunctive properties of BER led to an increase in antimicrobial effectiveness for these antibiotics against the corresponding bacteria, a decrease in minimal inhibitory concentrations, and even the reversal from resistance to susceptibility sometimes. The potential mechanisms responsible for these effects included the inhibition of antibiotic efflux, the disruption of biofilm formation, the modulation of host immune responses, and the restoration of gut microbiota homeostasis. In brief, BER demonstrated significant potential as an antibiotic adjuvant against MDR bacteria and is a promising candidate for combination therapy. Further research is necessary to fully elucidate its mechanism of action and address the challenges associated with its clinical application.

Advanced drug delivery and therapeutic strategies for tuberculosis treatment.

Tuberculosis (TB) remains a significant global health challenge, necessitating innovative approaches for effective treatment. Conventional TB therapy encounters several limitations, including extended treatment duration, drug resistance, patient noncompliance, poor bioavailability, and suboptimal targeting. Advanced drug delivery strategies have emerged as a promising approach to address these challenges. They have the potential to enhance therapeutic outcomes and improve TB patient compliance by providing benefits such as multiple drug encapsulation, sustained release, targeted delivery, reduced dosing frequency, and minimal side effects. This review examines the current landscape of drug delivery strategies for effective TB management, specifically highlighting lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, emulsion-based systems, carbon nanotubes, graphene, and hydrogels as promising approaches. Furthermore, emerging therapeutic strategies like targeted therapy, long-acting therapeutics, extrapulmonary therapy, phototherapy, and immunotherapy are emphasized. The review also discusses the future trajectory and challenges of developing drug delivery systems for TB. In conclusion, nanomedicine has made substantial progress in addressing the challenges posed by conventional TB drugs. Moreover, by harnessing the unique targeting abilities, extended duration of action, and specificity of advanced therapeutics, innovative solutions are offered that have the potential to revolutionize TB therapy, thereby enhancing treatment outcomes and patient compliance.

A novel antimicrobial peptide Scyreptin1-30 from Scylla paramamosain exhibiting potential therapy of Pseudomonas aeruginosa early infection in a mouse burn wound model.

Antimicrobial resistance (AMR) constitutes a significant global threat to human health. In recent years, there has been a concerning surge in infections caused by multidrug-resistant bacteria, highlighting the pressing need to urgently explore novel and effective alternatives to conventional antibiotics. Antimicrobial peptides (AMPs) have emerged as a focal point of research, capturing significant attention as promising antimicrobial agents. In this study, we have identified a novel cationic antimicrobial peptide (AMP) named Scyreptin1-30, derived from the marine invertebrate Scylla paramamosain. The results showed that Scyreptin1-30 exhibits a broad-spectrum antimicrobial activity, demonstrating significant potency against both bacteria and fungi, and even against the clinically isolated multidrug-resistant bacteria Pseudomonas aeruginosa. Moreover, Scyreptin1-30 exhibited rapid bactericidal kinetic. The results of antibacterial mechanism showed that Scyreptin1-30 destroyed the integrity of bacterial membranes, leading to bacterial death and exhibited potent anti-biofilm activity against P. aeruginosa. The activity of Scyreptin1-30 against bacteria had a favorable thermal stability, displayed a certain ion tolerance, and showed no discernible cytotoxicity when assessed against both the mammalian cell line HEK293T and the fish cell lines ZF4. In an In vivo study, Scyreptin1-30 exhibited a remarkably reduction in the bacterial load caused by multidrug-resistant P. aeruginosa at the site of infection, and promoted wound healing in a mouse model of burn infection. This study indicated that Scyreptin1-30 holds promise as an effective antibacterial agent, potentially serving as a topical skin treatment against multidrug-resistant bacterial infections, including those caused by P. aeruginosa.

Bacteriophage treatment as an alternative therapy for multidrug-resistant bacteria.

Multidrug-resistant (MDR) bacteria constitute one of the most serious global health threats. The increasing incidence rate of bacterial infections caused by MDR strains and the decrease in the number of newly developed antibiotics have prompted the scientific community to search for alternatives. One such alternative is the use of bacteriophages. In this review, we discuss the most critical MDR organisms, including Acinetobacter baumanni, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus The efficacy of phage therapy against MDR bacteria is also discussed. We included studies from the last 10 years that examined the efficacy of phage therapy against MDR pathogens. In addition, this review highlights the effect of bacteriophages against bacterial biofilms. The existing knowledge indicates that phage therapy is a potential therapeutic strategy against MDR bacteria. However, the adverse effects of phage therapy, such as toxicity, and the emergence of phage resistance have not yet been resolved.

Carriage of multidrug-resistant carbapenemase-producing gram-negative bacteria in patients admitted to NHS Greater Glasgow and Clyde hospitals: Implications for treatment.

BACKGROUND: Infections caused by gram-negative carbapenemase-producing organisms (CPO) have become a global phenomenon. Screening of patients for CPO that was carried out at 48-h intervals enables early detection of carriers for infection control purposes and planning therapy. METHODS: We investigated the bacterial flora detected on screening, the enzymes that conferred resistance and the proportion of patients who developed bacteraemia with CPO and their therapy. RESULTS: In all, 27 patients had a positive screen for CPO. A small but significant (7.5%) proportion of patients were not detected on initial screening. Escherichia coli and Klebsiella were predominant. New-Delhi metallo ß-lactamase and oxacillin carbapenemases were the main enzymatic mechanisms of resistance. Four (14.8%) patients developed bacteraemia with CPO (30- and 90-day survival 100% and 75%, respectively). CONCLUSION: A single negative screen does not rule out colonisation. A significant proportion of patients colonised with CPO develop bacteraemia. Vigilance is needed to prevent the nosocomial spread of CPO.

The impact of the COVID-19 pandemic on hospital-acquired infections at a comprehensive cancer center.

BACKGROUND: Robust infection prevention and control (IPC) measures were deployed across health care institutions at the start of the COVID-19 pandemic, resulting in increased use of personal protective equipment, enhanced contact precautions, and an emphasis on hand hygiene. Here, we evaluate the effect of enhanced IPC practices on the occurrence of various hospital-associated infections (HAIs) in a comprehensive cancer center. METHODS: From September 2016 through March 2022, we calculated the incidence rates (IRs) of HAIs for C. difficile infection, multidrug-resistant organisms, respiratory viral infections (RVIs), and device-related infections. We analyzed the incidence rate ratios for all HAIs during the periods before the pandemic, during the pandemic, at the time of the surges, and in COVID-19-designated wards. RESULTS: When comparing the prepandemic to the pandemic period, the IR across all MRDOs was similar. We observed a decrease in the IR of central line-associated bloodstream infections and a stable IR of catheter-associated urinary tract infections. A significant decrease was observed in the IR of C. difficile infection. The total IR of nosocomial RVIs decreased, as did for each respiratory virus. A similar IR of nosocomial RVIs between COVID-19 community surge versus nonsurge periods was observed except for SARS-CoV-2, RSV, and influenza. multidrug resistant organisms were 5 times more likely to occur on the COVID-19 wards compared with the non-COVID-19 wards. CONCLUSIONS: Implementing strict IPC measures during the COVID-19 pandemic in a cancer hospital led to a significant decrease in many HAIs and a reduction in nosocomial RVIs.

Endophytic fungal species Nigrospora oryzae and Alternaria alternata exhibit antimicrobial activity against gram-positive and gram-negative multi-drug resistant clinical bacterial isolates.

BACKGROUND: The emergence of multidrug-resistant pathogens and the lack of new antimicrobial drugs is a major public health concern that needs urgent and innovative solutions. Endophytic fungi living in unique niches such as in endosymbiosis with plants are increasingly drawing attention as alternative sources of novel and chemically diverse compounds with unique mechanisms of action. METHODS: In the present study, ten endophytic fungi isolated from the medicinal plant, Sclerocarya birrea were screened for bioactivity against a panel of indicator bacteria. Three bioactive endophytic fungi (strains P02PL2, P02MS1, and P02MS2A) were selected and identified through ITS-rDNA sequencing. The whole broth extracts of the three selected isolates were further screened against contemporary drug-resistant bacterial pathogens. This was followed by partial purification by solid phase extraction and GC-MS analysis of bioactive fractions. RESULTS: The bioactive endophytic fungi were identified as Alternaria alternata species (strains P02PL2 and P02MS1) and Nigrospora oryzae (strain P02MS2A). The whole broth extracts from N. oryzae P02MS2A exhibited a MIC of one µg/mL and 16 µg/mL against gram-negative, MDR Pseudomonas 5625574 and gram-positive MRSA 25775 clinical isolates, respectively. After partial purification and GC-MS analysis of whole broth extract from A. alternaria PO2MS1, 2-fluorobenzoic acid heptadecyl was putatively identified as the active compound in fraction C of this extract. This compound was also putatively identified in fraction E of A. alternata P02PL2, fraction B of A. alternata P02MS1 and fraction B of N. oryzae P02MS2A, and interestingly, all these fractions retained activity against the two MDR clinical isolates. CONCLUSION: The putative identification of 2-fluorobenzoic acid heptadecyl compound showing a broad-spectrum of activity, more especially against gram-negative MDR contemporary pathogens is highly encouraging in the initiative at developing novel drugs to combat multi-drug resistance.

Caenorhabditis elegans as an In Vivo Model for the Discovery and Development of Natural Plant-Based Antimicrobial Compounds.

Antimicrobial resistance (AMR) due to the prevalence of multidrug-resistant (MDR) pathogens is rapidly increasing worldwide, and the identification of new antimicrobial agents with innovative mechanisms of action is urgently required. Medicinal plants that have been utilised for centuries with minor side effects may hold great promise as sources of effective antimicrobial products. The free-living nematode Caenorhabditis elegans (C. elegans) is an excellent live infection model for the discovery and development of new antimicrobial compounds. However, while C. elegans has widely been utilised to explore the effectiveness and toxicity of synthetic antibiotics, it has not been used to a comparable extent for the analysis of natural products. By screening the PubMed database, we identified articles reporting the use of the C. elegans model for the identification of natural products endowed with antibacterial and antifungal potential, and we critically analysed their results. The studies discussed here provide important information regarding "in vivo" antimicrobial effectiveness and toxicity of natural products, as evaluated prior to testing in conventional vertebrate models, thereby supporting the relevance of C. elegans as a highly proficient model for their identification and functional assessment. However, their critical evaluation also underlines that the characterisation of active phytochemicals and of their chemical structure, and the unravelling of their mechanisms of action represent decisive challenges for future research in this area.