Broad-spectrum Antimicrobial Agents Research Articles

Cholic-Acid Derived, Guanidine-Functionalized Polymers as Broad-Spectrum Antimicrobial Agents

Cholic-Acid Derived, Guanidine-Functionalized Polymers as Broad-Spectrum Antimicrobial Agents

Multi-Lasso Peptide-Based Synergistic Nanocomposite: A High-Stability, Broad-Spectrum Antimicrobial Agent with Potential for Combined Antibacterial Therapy.

Lasso peptides, natural biological microcins composed of small molecules, have demonstrated efficient bactericidal activity. However, a single lasso peptide is characterized by a narrow and targeted bactericidal spectrum. In this study, a chitosan (CN) derivative-based polymer nanomaterial incorporating three lasso peptides (MccY, MccJ25, and Klebsidin) was designed and synthesized to broaden its antimicrobial spectrum. To enhance resistance to acid and alkali conditions, arginine was appended to the terminus of conjugates, resulting in Chitosan-Lasso-Peptides-Arg (CN-LPs-Arg), and the nanomaterial biocompatibility and bactericidal activity were characterized. Chemical stability test results demonstrate that CN-LPs-Arg effectively buffered the acid-base effect of the compound. Notably, CN-LPs-Arg extended the antimicrobial spectrum of Gram-negative and Gram-positive strains including Klebsiella, Salmonella, and Staphylococcus (MIC = 0.01-1.0 μM). CN-LPs-Arg exerts its destructive effects on bacteria via a series of mechanisms; it adheres to and then penetrates the membrane, causes rupture, and leads to bacterial death. Transcriptomic data revealed that CN-LPs-Arg produced a distinct inhibitory effect on ribosomal protein subunits synthesis pathways and membrane metabolic inhibition. Furthermore, CN-LPs-Arg was nontoxic to cells and exhibited excellent biocompatibility. CN-LPs-Arg reduced bacterial burden in organs and the levels of inflammatory factors IL-6, IL-8, and TNF-α in tissues of mice with acute bacterial infections. Furthermore, it promoted the recovery of Klebsiella-infected C57BL/6 mice, demonstrating a favorable therapeutic effect in vivo. The multilasso peptide-based synergistic nanocomposite of CN-LPs-Arg exhibited high stability as a broad-spectrum antimicrobial agent with potential for combined antibacterial therapy and utilization in the fields of food, biomedicine, and public health.

Omiganan-Based Synthetic Antimicrobial Peptides for the Healthcare of Infectious Endophthalmitis.

Bacterial endophthalmitis is a severe infection of the aqueous or vitreous humor of the eye that can lead to permanent vision loss. Due to the rapid emergence of antibiotic resistance and dose-limiting toxicities, the standard treatment of bacterial endophthalmitis via the intravitreal injection of broad-spectrum antibiotics remains inadequate. Membrane active cationic antimicrobial peptides (AMPs) have emerged as a promising class of effective and broad-spectrum antimicrobial agents with potential to overcome antibiotic resistance. In this work, we investigate, for the first time, the use of omiganan (IK-12), a 12-amino acid indolicidin derivative for the treatment of bacterial endophthalmitis. Additionally, IK-12 was used as a template to perform amino acid rearrangements, without altering the length or type of amino acids, to yield a series of new derivative AMPs with varying extents of secondary structure formation under membrane mimicking conditions. IK-12 and its derivatives demonstrated strong and broad-spectrum antibacterial activities against a panel of clinically isolated Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus commonly implicated in bacterial endophthalmitis. Interestingly, two of the new IK-12 derivatives, IP-12 and WP-12, showed lower geometric mean minimum inhibitory concentration and higher 50% hemolysis concentration values, which effectively translated into 2- to 3.4-fold higher bacterial selectivity than the parent IK-12. Furthermore, the intravitreal injection of IK-12, IP-12, and WP-12 in a rabbit model of MRSA-induced endophthalmitis led to considerably improved clinical presentation and reduced recruitment of inflammatory cells. In all, these results demonstrate the potential of IK-12 and its derivatives, IP-12 and WP-12, as promising candidates for the treatment of bacterial endophthalmitis.

Eco-Friendly and Low-Cost Synthesis of Transparent Antiviral- and Antibacterial-Coated Films Based on Cu2O and MIL-53(Al).

This research presents the development of an innovative antimicrobial coating consisting of cuprous oxide (Cu2O) integrated with the metal-organic framework MIL-53(Al) through an eco-friendly and low-cost synthesis method that employs glucose as a reducing agent under mild conditions. The microstructural properties of the composite materials were characterized by using X-ray diffraction (XRD) and transmission electron microscopy (TEM). The antibacterial efficacy of the Cu2O-MIL-53(Al) (CuM) composite was assessed against Escherichia coli and Staphylococcus aureus, achieving a reduction efficacy of 99.99% with 5% copper incorporated into the MIL-53(Al) framework within a contact time of 24 h. The incorporation of CuM into a macromolecular host matrix of polyurethane-carboxymethylcellulose (CuM/PUD-CMC), applied as a coating on a low-cost plastic film, produced a transparent film with 87.10% transparency. This coating demonstrated a 99.99% reduction in E. coli and S. aureus populations within a contact time of 24 h. The CuM/PUD-CMC coating demonstrated substantial antiviral efficacy, achieving inactivation rates of 99.35% for Human Coronavirus 229E, 99.40% for Influenza A virus, and 97.76% for Enterovirus 71 within a contact time of 5 min. The CuM nanoparticles exhibited low toxicity toward zebrafish while effectively eradicating bacteria and inactivating viruses. The proposed low-cost material and coating method demonstrate significant potential as a broad-spectrum antimicrobial and antiviral agent, highlighting its suitability for various applications in biomedical and healthcare formulations.

Gut microbiome as biomarker for triclosan toxicity in Labeo rohita: bioconcentration, immunotoxicity and metagenomic profiling.

Triclosan (TCS) is a lipophilic, broad spectrum antimicrobial agent commonly used in personal care products with a projected continuous escalation in aquatic environments in the post COVID 19 era. There is rich documentation in the literature on the alteration of physiological responses in fish due to TCS exposure; however, studies on gut associated bacteria of fish are still scarce. This is the first attempt to determine changes in bacterial community structure due to exposure of TCS on Labeo rohita, a commercially essential freshwater species, using 16S V3-V4 region ribosomal RNA (rRNA) next-generation sequencing (NGS). Chronic exposure of TCS at environmentally realistic concentrations viz. 1/5th (T1: 0.129 mg/L) and 1/10th (T2: 0.065 mg/L) of LC50 for 28 days resulted in the dose dependent bioconcentration of TCS in the fish gut. Prolonged exposure to TCS leads to disruption of gut bacteria evidenced by down regulation of the host immune system. Additionally, high-throughput sequencing analysis showed alternation in the abundance and diversity of microbial communities in the gut, signifying Proteobacteria and Verrucomicrobia as dominant phyla. Significant changes were also observed in the relative abundance of Chloroflexi and Gammatimonadetes phyla in TCS exposed groups. The study revealed that gut microbiome can be used as a biomarker in assessing the degree of TCS toxicity in commercially important fish species.

Antimicrobial activities of modified and unmodified pectin obtained from peels of Irvingia gabonensis, Cola milleni, and Theobroma cacao on specific pathogenic organisms

The antibacterial and antifungal activities of ethanolic extracts of pectin derived from the peels of Theobroma cacao, Cola milleni, and Irvingia gabonensis were investigated against phytopathogenic bacteria and fungi. The agar diffusion method was employed to test the extracts against Staphylococus aureus, Pseudomonas aeroginosa, Chromobacterium violaceum, Streptococcus feacalis, Xanthomonas axonopodis, Erwinia carotovora, Sclerotium rulfsii, Pythophthora palmivora, and Pyricularia oryzae. Significant differences (p<0.05) were observed in all control groups. The extracts inoculated with Streptomycin exhibited the highest activity against all bacterial strains. Conversely, the unmodified extracts of pectin samples from cola, cocoa, and wild mango displayed the least inhibitory activity against the tested bacterial strains, while the modified extracts with Chloro Acetic Acid (CAA), Para Amino Benzoic Acid (PABA), and Para Nitro Benzoic Acid (PNBA) showed varying inhibitory effects. The control sample inoculated with Mancozeb demonstrated the highest zone of inhibition against all fungal strains in the three pectin samples. However, the modified pectin samples exhibited increased inhibitory effects compared to the unmodified pectin extract, although the results were closer to the control. The higher values of modified pectin can be attributed to the presence of modifying agents such as long-chain hydrocarbons, acetic acid, chloro compounds, carboxyl, benzene rings, amino groups, and nitro groups. The presence of secondary metabolites in the pectin samples may also contribute to the higher values observed in both modified and unmodified samples. Overall, the results indicate the fungicidal and bactericidal potential of the extracts against the tested organisms, suggesting their potential use as broad-spectrum antimicrobial agents.

INDUCTION OF PARTURITION IN A PYGMY HIPPOPOTAMUS (CHOEROPSIS LIBERIENSIS).

A 27-yr-old female pygmy hippopotamus (Choeropsis liberiensis) had two consecutive stillbirths with no overt signs of labor, suggestive of uterine inertia. After a third pregnancy was confirmed, an induction protocol was developed. Cloprostenol and betamethasone were administered on d 200 of gestation (time 0 h). Additional doses of cloprostenol were administered at 24 and 48 h and oxytocin at 30, 31, and 48 h. Each injection resulted in preparturient behavior without overt evidence of contractions. Fetal membranes presented at the vulva at 54.5 h after initial cloprostenol and betamethasone administration with no progression of labor. Transvaginal palpation and manual delivery of a live calf followed. Despite confirmed nursing, the serum glutaraldehyde coagulation test was negative. Failure of passive transfer may have been secondary to the induction protocol. The calf was treated with broad-spectrum antimicrobial agents due to diarrhea, and clinical signs resolved. This clinical brief details the first known induction of parturition in a pygmy hippopotamus, which can serve as the basis for further development of the technique.

Detection of csg and lux Genes in Biofilm-Forming Uropathogenic Escherichia coli Associated with Urinary Tract Infections

Uropathogenic Escherichia coli (UPEC) is responsible for 80–90% of urinary tract infections (UTI) in the global population. The emergence of the increasing resistance to broad-spectrum antimicrobial agents was due to the ability to form biofilms. Cell surface factors that play a role in biofilm formation include Quorum Sensing (QS) which is encoded by the luxS family gene and curli by two operons, namely the csgBA operon. The purpose of the study is to detect the effects of 2 virulence genes (csgD and luxS) on biofilm-forming UPEC associated with UTI. As many as 76 UPEC isolates were collected from the clinical microbiology laboratories and the biofilm development was analyzed using the crystal violet method on microplate 96 wells. Using PCR assay, the two studied genes (csgD and luxS) were determined to be present in the isolates. UPEC isolates the bacteria-produced biofilms (90.80%) and nonproducers (9.20%). Most UPEC bacteria (97.36%) are known to be positive for csgD and luxS gene, while the others (92.10%) are known to be positive for the luxS gene. The highest proportion of the genes expressed in this study is followed by the presence of a relationship between the ability to produce biofilm and the presence of the genes under investigation, which is followed by all UPEC strains that cause UTI in humans.

Novel Insights into the Antimicrobial and Antibiofilm Activity of Pyrroloquinoline Quinone (PQQ); In Vitro, In Silico, and Shotgun Proteomic Studies.

Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a natural medicinal drug involved in various cellular processes, holds promise as a potential antimicrobial agent. In the present study, our aim was, for the first time, to explore the antimicrobial activity of PQQ against 29 pathogenic microbes, including 13 fungal strains, 8 Gram-positive bacteria, and 8 Gram-negative bacteria. Our findings revealed potent antifungal properties of PQQ, particularly against Syncephalastrum racemosum, Talaromyces marneffei, Candida lipolytica, and Trichophyton rubrum. The MIC values varied between fungal strains, and T. marneffei exhibited a lower MIC, indicating a greater susceptibility to PQQ. In addition, PQQ exhibited notable antibacterial activity against Gram-positive and -negative bacteria, with a prominent inhibition observed against Staphylococcus epidermidis, Proteus vulgaris, and MRSA strains. Remarkably, PQQ demonstrated considerable biofilm inhibition against the MRSA, S. epidermidis, and P. vulgaris strains. Transmission electron microscopy (TEM) studies revealed that PQQ caused structural damage and disrupted cell metabolism in bacterial cells, leading to aberrant morphology, compromised cell membrane integrity, and leakage of cytoplasmic contents. These findings were further affirmed by shotgun proteomic analysis, which revealed that PQQ targets several important cellular processes in bacteria, including membrane proteins, ATP metabolic processes, DNA repair processes, metal-binding proteins, and stress response. Finally, detailed molecular modeling investigations indicated that PQQ exhibits a substantial binding affinity score for key microbial targets, including the mannoprotein Mp1P, the transcriptional regulator TcaR, and the endonuclease PvuRTs1I. Taken together, our study underscores the effectiveness of PQQ as a broad-spectrum antimicrobial agent capable of combating pathogenic fungi and bacteria, while also inhibiting biofilm formation and targeting several critical biological processes, making it a promising therapeutic option for biofilm-related infections.

Multivalent-copper-loaded layer-by-layer coating for antibacterial and instantaneous virucidal activity for protective textiles

Nanoarchitectured films are known for tailoring surface properties, while antimicrobial surfaces can reduce pathogen propagation in public spaces and on protective equipment. This study explores the layer-by-layer (LbL) method to create antiviral and antibacterial surfaces against disease transmission. Chitosan and carboxymethylcellulose films were assembled using LbL to incorporate ionic copper, a broad-spectrum antimicrobial agent, onto textile substrates, such as those used in furnishings and personal protective equipment. Film assembly conditions favored the conversion of Cu(II) into multivalent copper, immediately inactivating the MHV-3 virus, Gram-negative (E. coli), and Gram-positive (S. aureus) bacteria. Mechanical tests demonstrate that copper ions have a low impact on the coating and textile physical properties, such as elasticity, tensile strength, and film roughness, by promoting ionic crosslinking of chitosan in the film, while the coating kept air permeability. The coating hydrophilicity and copper release profile were also tuned by the deposition of additional hydrophobic barriers, such as L-alpha-phosphatidylcholine phospholipid or polydimethylsiloxane (PDMS) by spin-coating or plasma polymerization, respectively. Viral inactivation is achieved by the local release of copper ions in contaminated droplets. The coating may also act as a droplet-absorbing barrier, demonstrating the potential of these films for enhancing pathogen resistance and infection control in textile surfaces.

Chronic amoxicillin shortage led to alternative broad-spectrum antimicrobial use in pediatric clinics

This study aimed to clarify changes in antimicrobial prescribing trends in pediatric clinics before and after the chronic shortage of amoxicillin and amoxicillin-clavulanic acid from 2023 in Japan. Amoxicillin and amoxicillin-clavulanic acid have been in chronic short supply since May 24, 2023 due to increased demand. It is unclear whether this situation has changed the type of oral antimicrobials prescribed by clinics. A retrospective observational study was conducted to analyze antimicrobial prescriptions in pediatric clinics between January and December 2023. The data was collected using information available on a new platform, the Online Monitoring System for Antimicrobial Stewardship at Clinics (OASCIS). The period from March to May was defined as the pre-shortage period, and the period from June to August was defined as the post-shortage period. Antimicrobials were classified using the AWaRe classification proposed by the World Health Organization. The average prescription rate per AWaRe classification in the three months before and after the shortage was compared. A total of 28,888 oral antimicrobial prescriptions were collected. Due to the chronic shortage, the proportion of Access antimicrobials decreased from 53.9 % in the pre-shortage period to 46.8 % in the post-shortage period (p < 0.001). The proportion of Watch antimicrobials increased from 45.9 % to 52.8 % (p < 0.001). Among the Watch antimicrobials, prescriptions for third-generation cephalosporins increased from 18.8 % to 24.7 % (p < 0.001). The chronic shortage of amoxicillin and amoxicillin-clavulanic acid has led to the use of broad-spectrum antimicrobial agents for patients in pediatric clinics.

Antibacterial Iodine-Releasing Coatings of Cross-Linked Poly(N-vinylpyrrolidone) Synthesized by Solvent-Free Initiated Chemical Vapor Deposition.

Biomaterial-associated infections caused by bacteria pose a great threat to human health, and therefore, various antibacterial coatings have been developed to control bacterial infections. Povidone iodine (PVP-I) is a broad-spectrum antimicrobial agent without drug resistance to most pathogenic microorganisms and has been widely used in the clinic. However, its applications in the field of coatings are limited due to its strong water solubility. Here, we used initiated Chemical Vapor Deposition (iCVD) technique to synthesize cross-linked poly(N-vinylpyrrolidone-co-ethylene glycol dimethacrylate) (PVE) coatings to firmly immobilize poly(N-vinylpyrrolidone) (PVP) on surfaces. After complexation with iodine, PVE-I coatings exhibited potent bacteria-killing and antifouling activities against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus in vitro owing to the antibacterial effect of iodine and the hydrophilicity of VP, respectively. The killing and antifouling effects were positively correlated with the VP content. The PVE-I-2 coating displayed excellent anti-infection performance in a rat subcutaneous implantation model in vivo. This study provided a simple method for preparing stable povidone iodine coatings on surfaces via solvent-free iCVD, and combined bacteria-killing and antifouling strategies to fabricate multifunctional antibacterial coatings against bacterial infections on biomaterial surfaces.

N-Chlorotaurine Solutions as Agents for Infusion Detoxification Therapy: Preclinical Studies.

N-chlorotaurine (NCT) is a broad-spectrum antimicrobial agent with outstanding tolerability, effective for topical and inhalation use. This paper presents the results of studies of single and repeated intravenous infusions of NCT to laboratory animals. The studies were conducted on female Wistar Han rats. The effect of NCT infusions on the general condition, behavioral reactions, main biochemical and hematological parameters, hemocoagulation system, cardiovascular system, and on the condition of the internal organs was studied. It was found that NCT infusions do not reveal deviations in the studied parameters that could indicate a toxic effect. The estimated LD50 is more than 80 mg/kg. In a subchronic experiment, a statistically significant decrease in cholesterol (by up to 11%), glucose (by up to 15%) and excess bases (up to four times) in the blood, and an increase in heart rate (by up to 31%) and frequency of defecations (by up to 35%), as well as pronounced antiplatelet effect, were found. In animals with simulated endotoxicosis, a decrease in the cytolysis and oxidative stress markers was observed. Such effects are caused by both chlorine-active compounds and taurine.The results obtained indicate broad prospects for the use of NCT solutions as an infusion detoxifying agent.

Analytical and Antimicrobial Characterization of Zn-Modified Clays Embedding Thymol or Carvacrol.

Carvacrol and thymol are broad-spectrum natural antimicrobial agents. To reduce their volatility and improve their antimicrobial performance, synergistic systems were prepared loading the active molecules in zinc-modified clays. Montmorillonite (MMT) and zeolite (ZEO) were modified with zinc ions (ZnMMT and ZnZEO), with well-known antimicrobial properties, and then with carvacrol or thymol, reaching the 26 ± 3% and 33 ± 2% w/w of loading, respectively. The resulting hybrid materials were characterized by FT-IR, XPS, XRD, TGA, and GC-MS to evaluate carvacrol/thymol release in simulating food matrices. Antimicrobial assays carried out using spoiler and pathogenic bacterial strains showed that the antimicrobial activity of both thymol and carvacrol was largely preserved once they were loaded into Zn-modified clays. However, MMT hybrids showed an antibacterial activity significantly higher than ZEO hybrids at 50 mg/mL of thymol and carvacrol. For this reason, deeper antimicrobial evaluations were carried out only for ZnMMT composites. ZnMMT loaded with thymol or carvacrol produced inhibition zones against most of the target strains, also at 3.12 mg/mL, while the positive controls represented by the single molecule thymol or carvacrol were not active. The hybrid materials can be useful for applications in which the antimicrobial activity of natural molecules need to be displayed over time as requested for the control of microbial pathogens and spoilage bacteria in different applications, such as active packaging, biomaterials, and medical devices.

Feasibility of Narrow-Spectrum Antimicrobial Agents for Post-Operative Intra-Abdominal Infections After Gastrectomy.

Introduction: Recently, antimicrobial resistance has received considerable attention. Broad-spectrum antimicrobial agents are recommended as the initial therapy for post-operative intra-abdominal infections. However, at our institution, we have adopted a tactic of initially treating post-operative intra-abdominal complications with relatively narrow-spectrum antimicrobial agents, such as second-generation cephalosporins. In the present study, we aimed to retrospectively analyze the use of antimicrobial agents and the resulting treatment outcomes in patients with intra-abdominal complications after gastrectomy at our facility. Methods: We conducted a retrospective observational study of patients treated with antibiotic agents for intra-abdominal infectious complications after gastrectomy between 2011 and 2021. We determined the proportion of "initial treatment failures" associated with the initial administration of antibiotic agents for post-operative intra-abdominal complications. Results: Post-operative intra-abdominal infections were observed in 29 patients. Broad-spectrum antimicrobial agents were not administered. We successfully treated 19 patients. Initial treatment failure was observed in 10 patients, of whom five experienced failure due to bacterial resistance to the initial antimicrobial agent. All 10 patients who experienced initial treatment failure were discharged after drainage procedures or other treatments. There were no deaths due to post-operative complications. Cefmetazole was used as the initial antimicrobial agent in 27 of the 29 patients. Conclusions: Considering that all patients with post-gastrectomy intra-abdominal infections were successfully treated using relatively narrow-spectrum antimicrobial agents, and initial treatment failure due to antimicrobial-resistant pathogens was 17.2%, the use of narrow-range antimicrobial agents for intra-abdominal infections after gastrectomy can be deemed appropriate.

Antibacterial and anticancer activities of cardamom volatile oil and its application in food covering

Phytochemicals and bioactive compounds in medicinal plants significantly benefit human health and well-being. Cardamom essential oil (CEO) exhibits potential as a broad-spectrum antimicrobial and anticancer agent. A modified Kirby-Bauer disc diffusion technique was used to test cardamom essential oil’s antimicrobial activity and identify the inhibition zone. Staphylococcus aureus (ATCC 6538) and Bacillus cereus (ATCC6629) are two examples of Gram-positive bacteria against which the essential oil was evaluated for antibacterial activity. Gram-negative microorganisms such as Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC25922), and yeast Candida albicans were also evaluated for antimicrobial activity. The essential oil was assessed further against human liver (HEPG-2) and breast (MCF7) cell lines for anticancer properties. The findings suggest that, compared to the control, cardamom essential oil exhibits a significant zone of inhibition against all types of microbes except Pseudomonas aeruginosa. Additionally, for anti-cancer actions, the IC50 values were 42.3 µg/ml for MCF7 and 54 µg/ml for HEPG-2 cell lines, while IC90 results for MCF7 were 68.9 µg/ml and for HEPG-2 cell line were 80.7 µg/ml. The essential oil was developed in functional coating to preserve the postharvest mango fruit for 60 days at cold storage. The treated fruit showed reduced weight loss (10%), with a relative reduction of 78% compared to the control, chilling injury incidence (2.5%) at day 45, and rind pitting (3%) at day 30 compared to the control. This therapeutic plant may yield novel compounds for broad-spectrum antimicrobial and anticancer medicines and be transformed into economical and secure standardized herbal products.

In Vitro Efficacy of Silver Carbene Complexes, SCC1 and SCC22, Against Some Enteric Animal Pathogens

Silver carbene complexes (SCCs), a group of novel silver-based compounds capable of gradually releasing silver ions, have shown significant antimicrobial activity against a wide range of bacterial pathogens mainly isolated from human cases. The antimicrobial activity against animal isolated pathogens has yet been done. The in vitro efficacy of two SCCs with different carrier molecules (SCC1 with a methylated caffeine backbone and SCC22 with a dichloroimidazolium backbone) was investigated against three important animal and human pathogen species. SCC1 and SCC22 exhibited bacteriostatic and bactericidal effects against multidrug resistant Salmonella Typhimurium (poultry isolate), E. coli 843 and E. coli 1568 (swine isolates), and the poultry field isolates Salmonella Heidelberg, Salmonella Enteritidis, and Salmonella Montevideo with MICs and MBCs ranged from 16-21 µM (6-8 µg/mL) and 16-32 µM (6-12 µg/mL), respectively. Clostridium perfringens type A was sensitive to both SCC1 and SCC22 with the MICs being 11 (4 µg/mL) and 21 µM (8 µg/mL), respectively. These values were comparable to the MICs and MBCs for silver acetate. The MBCs against C. perfringens was &gt;85 µM for SCCs and &gt;192 µM for silver acetate (&gt;32 µg/mL for all compounds). Ten hours incubation of C. perfringens with 40 µg/mL of all three products showed down regulation of virulence genes plc and netB, suggesting viable cells and silver can modulate the virulence. Treating the C. perfringens with higher concentration (100 µg/mL) of each SCC for 10 hours inhibited more bacteria compared to the untreated bacterial cells, however, no differences in the ultrastructure of lysed bacteria were seen and this concentration might not induce viable but non-culturable (VBNC) state as suggested by transmission electron microscopy findings. SCCs showed a broad antimicrobial activity against all bacterial species tested including multidrug resistant pathogens. Both SCCs demonstrated inhibitory effect against the Gram-positive anaerobic C. perfringens type A which could have a high accumulation capacity for silver ion. These data suggest that SCCs may represent a novel class of broad-spectrumantimicrobial agents, which may be used to reduce the burden of pathogenic bacteria in the gastrointestinal tract of poultry.

Enhanced Antimicrobial Activity of AgCu Nanoparticles: The Role of Particle Size and Alloy Composition.

AgCu bimetallic· nanoparticles (NPs) represent a novel class of inorganic, broad-spectrum antimicrobial agents that offer enhanced antimicrobial effectiveness and reduced cytotoxicity compared to conventional Ag NP antibacterial materials. This study examines the antimicrobial performance and structural characteristics of AgCu nanoparticles (NPs) synthesized via two distinct chemical reduction processes using PVP-PVA as stabilizers. Despite identical chemical elements and sphere-like shapes in both synthesis methods, the resulting AgCu nanoparticles exhibited significant differences in size and antimicrobial properties. Notably, AgCu NPs with smaller average particle sizes demonstrated weaker antimicrobial activity, as assessed by the minimum inhibitory concentration (MIC) measurement, contrary to conventional expectations. However, larger average particle-sized AgCu NPs showed superior antimicrobial effectiveness. High-resolution transmission electron microscopy analysis revealed that nearly all larger particle-sized nanoparticles were AgCu nanoalloys. In contrast, the smaller particle-sized samples consisted of both AgCu alloys and monometallic Ag and Cu NPs. The fraction of Ag ions (relative to the total silver amount) in the larger AgCu NPs was found to be around 9%, compared to only 5% in that of the smaller AgCu NPs. This indicates that the AgCu alloy content significantly contributes to enhanced antibacterial efficacy, as a higher AgCu content results in the increased release of Ag ions. These findings suggest that the enhanced antimicrobial efficacy of AgCu NPs is primarily attributed to their chemical composition and phase structures, rather than the size of the nanoparticles.

Ciprofloxacin is a novel anti-ferroptotic antibiotic

Cancer patients undergoing chemotherapy are susceptible to various bacterial infections, necessitating prompt and precise antimicrobial treatment with antibiotics. Ciprofloxacin is a clinically utilized broad-spectrum antimicrobial agent known for its robust antiseptic activity. While ferroptosis, an oxidative form of cell death, has garnered attention as a promising avenue in cancer therapy, the potential impact of ciprofloxacin on the anticancer effects of ferroptosis remains unclear. This study seeks to investigate the potential influence of antibiotics on ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells. Here, we report a previously unrecognized role of ciprofloxacin in inhibiting ferroptosis in human PDAC cells. Mechanistically, ciprofloxacin suppresses erastin-induced endoplasmic reticulum (ER) stress through the activating transcription factor 6 (ATF6) and ER to nucleus signaling 1 (ERN1) pathway. Excessive ER stress activation can trigger glutathione peroxidase 4 (GPX4) degradation through autophagic mechanisms. In contrast, ciprofloxacin enhances the protein stability of GPX4, a crucial regulator that suppresses ferroptosis by inhibiting lipid peroxidation. Thus, our study demonstrates the anti-ferroptotic role of ciprofloxacin, highlighting the importance of careful consideration when contemplating the combination of ciprofloxacin with specific ferroptosis inducers in PDAC patients.

Enhanced Mechanical Strength and Sustained Drug Release in Carrier-Free Silver-Coordinated Anthraquinone Natural Antibacterial Anti-Inflammatory Hydrogel for Infectious Wound Healing.

The persistent challenge of healing infectious wounds and the rise of bacterial resistance represent significant hurdles in contemporary medicine. In this study, based on the natural small molecule drug Rhein self-assembly to form hydrogels and coordinate assembly with silver ions (Ag+), a sustained-release carrier-free hydrogel with compact structure is constructed to promote the repair of bacterial-infected wounds. As a broad-spectrum antimicrobial agent, Ag+ can avoid the problem of bacterial resistance caused by the abuse of traditional antibiotics. In addition, due to the slow-release properties of Rhein hydrogel, continuous effective concentration of Ag+ at the wound site can be ensured. The assembly of Ag+ and Rhein makes the hydrogel system with enhanced mechanical stability. More importantly, it is found that Rhein effectively promotes skin tissue regeneration and wound healing by reprogramming M1 macrophages into M2 macrophages. Further mechanism studies show that Rhein realizes its powerful anti-inflammatory activity through NRF2/HO-1 activation and NF-κB inhibition. Thus, the hydrogel system combines the excellent antibacterial properties of Ag+ with the excellent anti-inflammatory and tissue regeneration ability of Rhein, providing a new strategy for wound management with dual roles.