Broad-spectrum Antimicrobial Activity Research Articles

Characterization, Expression, and Functional Analysis of the Northern Snakehead (Channa argus) Hepcidin.

Hepcidin, an antimicrobial peptide (AMP), is a well-conserved molecule present in various species such as fish, amphibians, birds, reptiles, and mammals. It exhibits broad-spectrum antimicrobial activity and holds a significant role in the innate immune system of host organisms. The northern snakehead (Channa argus) has become a valuable freshwater fish in China and Asia. In this investigation, the cDNA encoding the hepcidin gene of northern snakehead was cloned and named caHep. The amino acid sequences and protein structure of caHep are similar to those of hepcidins from other fish. The eukaryotic expression product of the caHep gene showed broad-spectrum antibacterial activity. Scanning electron microscope analysis indicated that the caHep peptide inhibited bacterial growth by damaging their cell membranes. Lipopolysaccharide (LPS) injection induced significant expression of caHep, implying the involvement of caHep in the innate immune response of northern snakeheads. This investigation showed that the caHep peptide is potentially a robust antibacterial drug against bacterial diseases in aquaculture animals.

Two Antimicrobial Peptides Derived from Bacillus and Their Properties

Growth promotion and disease prevention are important strategies in the modern husbandry industry, and for this reason, antibiotics are widely used as animal feed additives. However, the overuse of antibiotics has led to the serious problem of increasing resistance of pathogenic microorganisms, posing a major threat to the environment and human health. “Limiting antibiotics” and “Banning antibiotics” have become the inevitable trends in the development of the livestock feed industry, so the search for alternative antimicrobial agents has become a top priority. Antimicrobial peptides (AMPs) produced by Bacillus spp. have emerged as a promising alternative to antibiotics, due to their broad-spectrum antimicrobial activity against resistant pathogens. In this study, two strains of Bacillus velezensis 9-1 and B. inaquosorum 76-1 with good antibacterial activity were isolated from commercial feed additives, and the antimicrobial peptides produced by them were purified by ammonium sulfate precipitation, anion exchange chromatography, gel chromatography, and RP-HPLC. Finally, two small molecule peptides, named peptide-I and peptide-II, were obtained from strain 9-1 and 76-1, respectively. The molecular weight and sequences of the peptides were analyzed and identified by LC–MS/MS, which were 988.5706 Da and VFLENVLR, and 1286.6255 Da and FSGSGSGTAFTLR, respectively. The results of an antibacterial activity and stability study showed that the two peptides had good antibacterial activity against Staphylococcus aureus, B. cereus, and Salmonella enterica, and the minimum inhibitory concentrations were 64 μg/mL and 16 μg/mL, 32 μg/mL and 64 μg/mL, and 8 μg/mL and 8 μg/mL, respectively. All of them have good heat, acid, and alkali resistance and protease stability, and can be further developed as feed antibiotic substitutes.

Endophytic bacteria Klebsiella spp. and Bacillus spp. from Alternanthera philoxeroides in Madiwala Lake exhibit additive plant growth-promoting and biocontrol activities

BackgroundThe worldwide increase in human population and environmental damage has put immense pressure on the overall global crop production making it inadequate to feed the entire population. Therefore, the need for sustainable and environment-friendly practices to enhance agricultural productivity is a pressing priority. Endophytic bacteria with plant growth-promoting ability and biocontrol activity can strongly enhance plant growth under changing environmental biotic and abiotic conditions. Herein, we isolated halotolerant endophytic bacteria from an aquatic plant, Alternanthera philoxeroides, from the polluted waters of Madiwala Lake in Bangalore and studied their plant growth promotion (PGP) and biocontrol ability for use as bioinoculant. ResultsThe isolated bacterial endophytes were screened for salt tolerance ranging from 5 to 15% NaCl concentration. Klebsiella pneumoniae showed halotolerant up to 10% NaCl and Bacillus amyloliquefaciens and Bacillus subtilis showed up to 15%. All three strains demonstrated good PGP abilities such as aminocyclopropane-1-carboxylic acid (ACC) deaminase activity, phosphate solubilization, ammonia production, and nitrogen fixation. In addition, K. pneumoniae also exhibited high indoleacetic acid (IAA) production (195.66 ± 2.51 µg/ml) and potassium solubilization (2.13 ± 0.07 ppm). B. amyloliquefaciens and B. subtilis showed good extracellular enzyme production against cellulase, lipase, protease, and amylase. Both the isolates showed a broad spectrum of antimicrobial activity against the tested organisms. The optimization of IAA production by K. pneumoniae was done by the response surface methodology (RSM) tool. Characterization of IAA produced by the isolate was done by gas chromatography-mass spectrometry (GCMS) analysis. The enhanced plant growth-promoting ability of K. pneumoniae was also demonstrated using various growth parameters in a pot trial experiment using the seeds of Vigna unguiculata. ConclusionThe isolated bacterial endophytes reported in this study can be utilized as PGP promotion and biocontrol agents in agricultural applications, to enhance crop yield under salinity stress. The isolate K. pneumoniae may be used as a biofertilizer in sustainable agriculture and more work can be done to optimize the best formulations for its application as a microbial inoculant for crops.

Evaluation of the impact of tragacanth/xanthan gum interpolymer complexation with chitosan on pharmaceutical performance of gels with secnidazole as potential periodontal treatment

Periodontitis consists a group of dental disorders that affect about 70 % of the world population. The therapy mainly relies on mechanical removing bacterial biofilm, nevertheless, local or systemic antibacterial agents play a key role in treating the acute conditions. Secnidazole is a newer derivative of commonly used metronidazole with high safety profile and broad spectrum of antimicrobial activity. The aim of the study was to evaluate the applicability of polyelectrolyte complex-based hydrogels composed of anionic tragacanth with addition of xanthan gum and cationic chitosan as carriers for buccal/intra pocket delivery of secnidazole. Prepared hydrogels with 5 % and 10 % (w/w) drug content were evaluated pharmaceutically towards inter alia physicomechanical, rheological and thermal properties, drug release kinetics, swelling behavior or antimicrobial activity. Cytotoxicity against human primary umbilical vein endothelial cells was also assessed with two independent method. Stable compositions with secnidazole were obtained, however, various miscibility of the drug with the polymers was noted. By adding chitosan, antibacterial activity and swelling performance of the gels were improved, nevertheless, drop of the mucoadhesiveness was also recorded. Hydrogels with 5 % secnidazole were selected as effective antimicrobial compositions with the highest cytocompatibility. They might be considered as promising for oromucosal application with special attention given to SEC as an alternative locally administered antimicrobial agent.

Neurotoxic effects of a well known antibiotic!

To the Editor, Cefepime is a fourth-generation cephalosporin with broad-spectrum antimicrobial activity covering a wide range of both gram-negative and gram positive organisms. It is administered parenterally to treat pneumonia, urinary tract infections as well as skin and soft tissue infections. It is generally well tolerated with the most commonly reported side effects being diarrhea and rash. However, cefepime induced neurotoxicity is a rare but life- threatening adverse effect that, despite being described in literature, is often overlooked. According to the literature, about 15% of ICU patients managed with cefepime may develop neurological symptoms, including altered consciousness, aphasia, myoclonus, encephalopathy, seizures and coma. EEG abnormalities such as non-convulsive status epilepticus, myoclonic status epilepticus, triphasic waves and focal sharp waves have also been reported. Risk factors for cefepime neurotoxicity include renal function impairment, overdosing, previous brain injury and elevated serum cefepime concentrations.1 A case study published in 2021 reported a rare case of cefepime induced neurotoxicity where an elderly female suffering from chronic renal transplant rejection was given cefepime. Despite renal dosage adjustment, the patient developed neurotoxicity and presented with acute delirium, inability to tolerate oral intake and non-convulsive status epilepticus on EEG. Discontinuation of cefepime resulted in improvement of symptoms.2 Another case series published in 2017 reported cefepime induced neurotoxicity in 3 patients, one of whom had normal kidney function. These patients presented with asynchronous myoclonus and expressive aphasia.3 Considering the common use of cefepime in hospital settings, it is very important to heed the possible neurological adverse effects of this antibiotic which can be potentially fatal. Cefepime should be used with caution especially in individuals with preexisting renal impairment. Fortunately, cefepime neurotoxicity is reversible and usually resolves with discontinuation of the drug. In a few cases, dialysis may be needed to hasten the elimination of the drug.4 Anticonvulsants may be needed if patient presents with seizures or non-convulsive status epilepticus.5 Since treatment is simple and recovery rates are good, prompt recognition is crucial. Especially in ICU patients, recognition of cefepime induced neurotoxicity is challenging as it may present with neurological symptoms that are common in critically ill patients. Therefore, ICU patients receiving cefepime should be closely monitored. It is of vital importance to raise awareness regarding the neurotoxic effects of cefepime to facilitate early recognition which will help reduce morbidity and mortality associated with this drug.

Functional characterization of group Ⅱ interferon, IFNf in the acipenseriform fish, Chinese sturgeon (Acipenser sinensis)

Teleost fish possess a diversity of type Ⅰ interferons (IFNs) repertoire, which play a crucial role in antiviral and antimicrobial immune responses. In our previous study, IFNe1-3 and IFNb were identified and cloned from Chinese sturgeon (Acipenser sinensis), an acipenseriform fish. However, the absence of Chinese sturgeon genome data has left the question of whether there are other type Ⅰ IFN members in this species unresolved. In this study, we have identified and characterized a novel IFN, IFNf in Chinese sturgeon (AsIFNf). Bioinformatics analysis revealed that the AsIFNf contains a unique disulfide bond (2 cysteines) located in the second exon and fifth exon region, distinguishing it from other reported teleost type I IFNs. Meanwhile, qPCR results showed that AsIFNf mRNA was detectable in all examined tissues and up-regulated in the spleen or kidney in response to poly I: C, Citrobacter freundii, and Spring Viremia of Carp Virus (SVCV), but not by LPS. Furthermore, compared to recombinant AsIFNe2 protein (rAsIFNe2), rAsIFNf exhibited a stronger protective effect on Chinese sturgeon fin cells against SVCV and also induced higher expression of antiviral genes Mx and viperin. Importantly, AsIFNf displayed characteristics similar to antimicrobial peptides (AMPs) with a positive charge and demonstrated a broad spectrum of antimicrobial activity in vitro. These findings provide a theoretical foundation for understanding the primitive structure and function of interferon, as well as deepening our comprehension of the innate immune system and disease defense in the endangered Chinese sturgeon.

Insights into the Mechanisms of Reuterin against Staphylococcus aureus Based on Membrane Damage and Untargeted Metabolomics.

Reuterin is a dynamic small-molecule complex produced through glycerol fermentation by Limosilactobacillus reuteri and has potential as a food biopreservative. Despite its broad-spectrum antimicrobial activity, the underlying mechanism of action of reuterin is still elusive. The present paper aimed to explore the antibacterial mechanism of reuterin and its effects on membrane damage and the intracellular metabolome of S. aureus. Our results showed that reuterin has a minimum inhibitory concentration of 18.25 mM against S. aureus, based on the 3-hydroxypropionaldehyde level. Key indicators such as extracellular electrical conductivity, membrane potential and permeability were significantly increased, while intracellular pH, ATP and DNA were markedly decreased, implying that reuterin causes a disruption to the structure of the cell membrane. The morphological damage to the cells was confirmed by scanning electron microscopy. Subsequent metabolomic analysis identified significant alterations in metabolites primarily involved in lipid, amino acid, carbohydrate metabolism and phosphotransferase system, which is crucial for cell membrane regulation and energy supply. Consequently, these findings indicated that the antibacterial mechanism of reuterin initially targets lipid and amino acid metabolism, leading to cell membrane damage, which subsequently results in energy metabolism disorder and, ultimately, cell death. This paper offers innovative perspectives on the antibacterial mechanism of reuterin, contributing to its potential application as a food preservative.

Antimicrobial Potential of Different Isolates of Chaetomium globosum Combined with Liquid Chromatography Tandem Mass Spectrometry Chemical Profiling.

The antimicrobial resistance of pathogenic microorganisms against commercial drugs has become a major problem worldwide. This study is the first of its kind to be carried out in Egypt to produce antimicrobial pharmaceuticals from isolated native taxa of the fungal Chaetomium, followed by a chemical investigation of the existing bioactive metabolites. Here, of the 155 clinical specimens in total, 100 pathogenic microbial isolates were found to be multi-drug resistant (MDR) bacteria. The Chaetomium isolates were recovered from different soil samples, and wild host plants collected from Egypt showed strong inhibitory activity against MDR isolates. Chaetomium isolates displayed broad-spectrum antimicrobial activity against C. albicans, Gram-positive, and Gram-negative bacteria, with inhibition zones of 11.3 to 25.6 mm, 10.4 to 26.0 mm, and 10.5 to 26.5 mm, respectively. As a consecutive result, the minimum inhibitory concentration (MIC) values of Chaetomium isolates ranged from 3.9 to 62.5 µg/mL. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis was performed for selected Chaetomium isolates with the most promising antimicrobial potential against MDR bacteria. The LC-MS/MS analysis of Chaetomium species isolated from cultivated soil at Assuit Governate, Upper Egypt (3), and the host plant Zygophyllum album grown in Wadi El-Arbaein, Saint Katherine, South Sinai (5), revealed the presence of alkaloids as the predominant bioactive metabolites. Most detected bioactive metabolites previously displayed antimicrobial activity, confirming the antibacterial potential of selected isolates. Therefore, the Chaetomium isolates recovered from harsh habitats in Egypt are rich sources of antimicrobial metabolites, which will be a possible solution to the multi-drug resistant bacteria tragedy.

Identification and immune analysis of antimicrobial peptides from the cigarette beetle (Lasioderma serricorne).

Antimicrobial peptides (AMPs) in insects are endogenous peptides that are effector components of the innate defense system of the insect. AMPs may serve as antimicrobial agents because of their small molecular weight and broad-spectrum antimicrobial activity. In this study, we performed transcriptome analysis of cigarette beetle (Lasioderma serricorne) larvae, parasitized by the ectoparasitic wasp, Anisopteromalus calandrae. Several AMP genes were significantly upregulated following A.calandrae parasitism, postulating the hypothesis that the parasitization enhanced the host's resistance against pathogenic microorganisms through the regulation of host AMP genes. Specifically, 3 AMP genes (LsDef1, LsDef2, and LsCole) were significantly upregulated and we studied their immune function in L.serricorne. Immune challenge and functional analysis showed that LsCole was responsible for the immune response against Gram-negative and Gram-positive bacteria, while LsDef1 and LsDef2 were involved in insect defense against Gram-positive bacteria. Purified recombinant LsCole exhibited antimicrobial activities against the Gram-negative bacterium Escherichia coli and the Gram-positive bacterium Staphylococcus aureus. LsDef2 showed an antibacterial effect against S.aureus. LsCole and LsDef2 exhibited antibiofilm activity against S.aureus. The 2 AMPs disrupted cell membranes and caused leakage of S.aureus cell contents. The results indicated that the 3 AMPs in L.serricorne are involved in the innate immunity of this pest insect. These AMPs may have potential as antimicrobial agents for bacterial infection chemotherapy. Hence, data are discussed in relation to new control strategies with greater biosafety against pest insects with use of microbial biocontrol agents in combination with RNA interference against the insect's defensive AMP genes.

Design and evaluation of tadpole-like conformational antimicrobial peptides

Antimicrobial peptides are promising alternatives to conventional antibiotics. Herein, we report a class of “tadpole-like” peptides consisting of an amphipathic α-helical head and an aromatic tail. A structure-activity relationship (SAR) study of “tadpole-like” temporin-SHf and its analogs revealed that increasing the number of aromatic residues in the tail, introducing Arg to the α-helical head and rearranging the peptide topology dramatically increased antimicrobial activity. Through progressive structural optimization, we obtained two peptides, HT2 and RI-HT2, which exhibited potent antimicrobial activity, no hemolytic activity and cytotoxicity, and no propensity to induce resistance. NMR and molecular dynamics simulations revealed that both peptides indeed adopted “tadpole-like” conformations. Fluorescence experiments and electron microscopy confirmed the membrane targeting mechanisms of the peptides. Our studies not only lead to the discovery of a series of ultrashort peptides with potent broad-spectrum antimicrobial activities, but also provide a new strategy for rational design of novel “tadpole-like” antimicrobial peptides.

Ceragenins exhibit bactericidal properties that are independent of the ionic strength in the environment mimicking cystic fibrosis sputum.

The purpose of the work was to investigate the impact of sodium chloride (NaCl) on the antimicrobial efficacy of ceragenins (CSAs) and antimicrobial peptides (AMPs) against bacterial and fungal pathogens associated with cystic fibrosis (CF) lung infections. CF-associated bacterial (Pseudomonas aeruginosa, Ochrobactrum spp., and Staphylococcus aureus), and fungal pathogens (Candida albicans, and Candida tropicalis) were used as target organisms for ceragenins (CSA-13 and CSA-131) and AMPs (LL-37 and omiganan). Susceptibility to the tested compounds was assessed using minimal inhibitory concentrations (MICs) and bactericidal concentrations (MBCs), as well as by colony counting assays in CF sputum samples supplemented with various concentrations of NaCl. Our results demonstrated that ceragenins exhibit potent antimicrobial activity in CF sputum regardless of the NaCl concentration when compared to LL-37 and omiganan. Given the broad-spectrum antimicrobial activity of ceragenins in the microenvironments mimicking the airways of CF patients, ceragenins might be promising agents in managing CF disease.

Impact of COVID-19 vaccination on saliva immune barriers: IgA, lysozyme, and lactoferrin.

Understanding the role of salivary constituents, such as lactoferrin, lysozyme, and secretory immunoglobulin A (sIgA), in immune protection and defense mechanisms against microbial invasion and colonization of the airways is important in light of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The salivary immune barrier in individuals affected by COVID-19 may contribute to disease prognosis. Thus, the aim of the present review is to evaluate the effect of COVID-19 vaccines on the immunological composition of saliva. IgA antibodies generated by vaccination can neutralize the virus at mucosal surfaces, whereas antimicrobial peptides, such as lysozyme and lactoferrin, have broad-spectrum antimicrobial activity. Collectively, these components contribute to the protective immune response of the oral cavity and may help minimize viral transmission as well as the severity of COVID-19. Measuring the levels of these components in the saliva of COVID-19-vaccinated individuals can help in evaluating the vaccine's ability to induce mucosal immunity, and it might also provide insights into whether saliva can be used in diagnostics or surveillance for monitoring immune responses following vaccination. This also has implications for viral transmission.

Ceragenins and Ceragenin-Based Core-Shell Nanosystems as New Antibacterial Agents against Gram-Negative Rods Causing Nosocomial Infections.

The growing number of infections caused by multidrug-resistant bacterial strains, limited treatment options, multi-species infections, high toxicity of the antibiotics used, and an increase in treatment costs are major challenges for modern medicine. To remedy this, scientists are looking for new antibiotics and treatment methods that will effectively eradicate bacteria while continually developing different resistance mechanisms. Ceragenins are a new group of antimicrobial agents synthesized based on molecular patterns that define the mechanism of antibacterial action of natural antibacterial peptides and steroid-polyamine conjugates such as squalamine. Since ceragenins have a broad spectrum of antimicrobial activity, with little recorded ability of bacteria to develop a resistance mechanism that can bridge their mechanism of action, there are high hopes that this group of molecules can give rise to a new family of drugs effective against bacteria resistant to currently used antibiotics. Experimental data suggests that core-shell nanosystems, in which ceragenins are presented to bacterial cells on metallic nanoparticles, may increase their antimicrobial potential and reduce their toxicity. However, studies should be conducted, among others, to assess potential long-term cytotoxicity and in vivo studies to confirm their activity and stability in animal models. Here, we summarized the current knowledge on ceragenins and ceragenin-containing nanoantibiotics as potential new tools against emerging Gram-negative rods associated with nosocomial infections.

Peracetic acid as an alternative disinfectant for micropollutants degradation and disinfection byproducts control in outdoor swimming pools

Peracetic acid (PAA) has garnered significant interest as a novel alternative to chlorine-based disinfectants for water treatment due to its broad-spectrum antimicrobial activity and its ability of reactive species generation when exposed to UV light. However, limited studies have investigated micropollutant degradation in the presence of PAA under solar irradiation. This is the first study to comprehensively investigate the photodegradation of caffeine (CAF) and 4-methylbenzylidene camphor (4-MBC) and the removal of disinfection byproducts (DBPs) in the presence of PAA under simulated solar light. The study revealed that the photodegradation of CAF and 4-MBC was significantly enhanced in the presence of PAA, following pseudo-first-order kinetics (R2 > 0.98) with reaction rates (kobs) of 0.220 and 0.111 h-1, respectively. In addition, substantial reduction of 21 DBPs, including trihalomethanes, haloacetic acids and haloacetonitriles, and no DBPs formation were observed in the presence of PAA and simulated solar irradiation. The proportion of coexisting H2O2 in the PAA solution considerably influenced target compounds degradation. CAF and 4-MBC were degraded faster under acidic conditions than under alkaline conditions. Hydroxyl radicals (·OH) dominated the degradation of CAF at different pH values, while direct photolysis and other reactive species played a major role in the degradation of 4-MBC.

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.

Candida albicans and Antifungal Peptides.

Candida albicans, a ubiquitous opportunistic fungal pathogen, plays a pivotal role in human health and disease. As a commensal organism, it normally resides harmlessly within the human microbiota. However, under certain conditions, C.albicans can transition into a pathogenic state, leading to various infections collectively known as candidiasis. With the increasing prevalence of immunocompromised individuals and the widespread use of invasive medical procedures, candidiasis has become a significant public health concern. The emergence of drug-resistant strains further complicates treatment options, highlighting the urgent need for alternative therapeutic strategies. Antifungal peptides (AFPs) have gained considerable attention as potential candidates for combating Candida spp. infections. These naturally occurring peptides possess broad-spectrum antimicrobial activity, including specific efficacy against C.albicans. AFPs exhibit several advantageous properties, such as rapid killing kinetics, low propensity for resistance development, and diverse mechanisms of action, making them promising alternatives to conventional antifungal agents. In recent years, extensive research has focused on discovering and developing novel AFPs with improved efficacy and selectivity against Candida species. Advances in biotechnology and synthetic peptide design have enabled the modification and optimization of natural peptides, enhancing their stability, bioavailability, and therapeutic potential. Nevertheless, several challenges must be addressed before AFPs can be widely implemented in clinical practice. These include optimizing peptide stability, enhancing delivery methods, overcoming potential toxicity concerns, and conducting comprehensive preclinical and clinical studies. This commentary presents a short overview of candidemia and AFP; articles and reviews published in the last 10years were searched on The National Library of Medicine (National Center for Biotechnology Information-NIH-PubMed). The terms used were C.albicans infections, antimicrobial peptides, antifungal peptides, antifungal peptides mechanisms of action, candidemia treatments and guidelines, synthetic peptides and their challenges, and antimicrobial peptides in clinical trials as the main ones. Older publications were cited if they brought some relevant concept or helped to bring a perspective into our narrative. Articles older than 20years and those that appeared in PubMed but did not match our goal to bring updated information about using antifungal peptides as an alternative to C.albicans infections were not considered.

Treatment of postpartum endometritis induced by multidrug-resistant bacterial infection in dairy cattle by green synthesized zinc oxide nanoparticles and in vivo evaluation of its broad spectrum antimicrobial activity in cow uteri

Postpartum endometritis significantly affects the health and productivity of cattle, causing significant economic loss that is speculated to exceed billions of dollars annually. Treatment of postpartum endometritis, which is linked to various bacterial infections in the uterus after delivery and has an alarmingly high risk of antibiotic treatment failure for unidentified reasons, represents a great challenge. Several studies have demonstrated that various disease complications, such as multidrug-resistant (MDR) bacterial strains, prolonged infection treatment, and increased mortality risk, have emerged as a result of the extensive use of antibiotics to treat uterine infections and other microbial-related diseases. Recent research has led to the development of zinc oxide nanoparticles (ZnO NPs) that exhibit broad-spectrum antibacterial efficacy against bacterial pathogens, including MDR bacteria, without producing mutants that are resistant to zinc oxide (ZnO). In the present work, we biologically synthesized ZnO NPs from a green natural source of Helianthus annuus seeds for the treatment of endometritis caused by MDR bacterial strains in dairy cattle. We examined ZnO's potential as a substitute antimicrobial agent to treat cow endometritis by testing its ability to sustain potent antimicrobial activity against pathogenic bacteria, including Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), in cow uteri. Among uterine bacteria, ZnO significantly decreased E. coli and S. aureus, which are known pathogenic bacteria within the uterus and achieved a high cure rate that was associated with the induction of estrous and pregnancy. Taken together, our observations of ZnO's broad range of antibacterial activity in-vivo with an animal model and subsequent evaluations of its therapeutic efficacy in cows with endometritis shed light on its potential to be used as a substitute antimicrobial agent for the treatment of uterine illness.

Synthesis, docking study and antimicrobial activity evaluation of pyridyl amides of thieno[2,3-d]pyrimidine-4-carboxylic acid

The aim. The combination in one molecule of pharmacophore fragments of thieno[2,3-d]pyrimidine-4-carboxylic acids with the fragments of 2- or 4-aminopyrimidine by peptide coupling promoted acylation in order to develop the new drug-like molecules with antimicrobial activity. Materials and methods. The molecular docking studies were performed with the AutoDock Vina та AutoDockTools 1.5.6 programs; TrmD Pseudomonas aeruginosa PDB ID – 5ZHN was used as the protein target. Synthetic methods of peptide coupling were used. 1H and 13C NMR spectra were recorded with a Varian-400 spectrometer at 400 MHz and Bruker Avance DRX 500 device at 500 MHz and 125 MHz in DMSO-d6 as a solvent, using TMS as the internal standard. LC-MS analysis of the compounds was carried out with Agilent 1100 HPLC з with atmospheric pressure chemical ionization (APCI). The studied derivates were tested in vitro for their antibacterial and anti-fungal activities using agar diffusion and serial dilutions resazurin-based microdilution assays (RBMA). Results and discussion. By the combination of the pharmacophore fragments of thieno[2,3-d]pyrimidine-4-carboxylic acids with the fragments of 2- of 4-aminopyrimidine, the combinatorial library of amides was constructed. For this library of compounds, the potential of antimicrobial activity was revealed using docking studies to the TrmD enzyme isolated from P. aeruginosa. The peptide coupling promoted by 1,1'-carbonyldiimidazole was found to be effective for the synthesis of pyridyl amides of thieno[2,3-d]pyrimidine-4-carboxylic acids, and it allowed to combine these pharmacophores in one molecule. The results of antimicrobial activity study revealed the broad spectrum of antimicrobial activity for N-(pyridin-4-yl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine-4-carboxamide (2g), while 5,6-dimethyl-N-(6-methylpyridin-2-yl)thieno[2,3-d]pyrimidine-4-carboxamide (2c) showed the best MIC value against the reference strain of Pseudomonas aeruginosa ATCC 10145. N-(6-Methylpyridin-2-yl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine-4-carboxamide (2h) was also found to be active against Pseudomonas aeruginosa. Conclusions. An effective method for the synthesis of pyridyl amides of thieno[2,3-d]pyrimidine-4-carboxylic acid has been developed. The amides molecular docking method showed their ability to inhibit TrmD enzyme isolated from P. aeruginosa; the further in vitro studies of the compounds showed the rationality of the further studies of the derivatives with 2-amino-6-methylpyridine in amide substituent because this fragment favoured the selectivity against Pseudomonas aeruginosa

Advanced biomaterial agent from chitosan/poloxamer 407-based thermosensitive hydrogen containing biosynthesized silver nanoparticles using Eucalyptus camaldulensis leaf extract.

The emergence of multidrug-resistant (MDR) pathogens poses a significant challenge for global public health systems, increasing hospital morbidity and mortality and prolonged hospitalization. We evaluated the antimicrobial activity of a thermosensitive hydrogel containing bio-synthesized silver nanoparticles (bio-AgNPs) based on chitosan/poloxamer 407 using a leaf extract of Eucalyptus calmadulensis. The thermosensitive hydrogel was prepared by a cold method after mixing the ingredients and left at 4°C overnight to ensure the complete solubilization of poloxamer 407. The stability of the hydrogel formulation was evaluated at room temperature for 3 months, and the absorption peak (420 nm) of the NPs remained unchanged. The hydrogel formulation demonstrated rapid gelation under physiological conditions, excellent water retention (85%), and broad-spectrum antimicrobial activity against MDR clinical isolates and ATCC strains. In this regard, minimum inhibitory concentration and minimum microbial concentration values of the bio-AgNPs ranged from 2-8 μg/mL to 8-128 μg/mL, respectively. Formulation at concentrations <64 μg/mL showed no cytotoxic effect on human-derived macrophages (THP-1 cells) with no induction of inflammation. The formulated hydrogel could be used in biomedical applications as it possesses a broad antimicrobial spectrum and anti-inflammatory properties without toxic effects on human cells.

Salicylaldehyde-functionalized polyethyleneimine precursor: Synthesis, characterization, and encapsulation in electrospun nonwoven for moisture-triggered release applications

Salicylaldehyde (SAL) is a natural flavoring agent with broad-spectrum antimicrobial activities but susceptible to degradation. To enhance its stability, SAL was conjugated with branched polyethyleneimine to form a SAL precursor (SALP) for controlled release applications. SAL molecules formed covalent bonds with BrPEI via imine linkages and imidazolidine rings, as confirmed by 1D and 2D NMR and FTIR spectroscopies. SALP was metastable under dry conditions but susceptible to acid-hydrolysis, triggering the release of SAL vapor, as revealed by the 1H NMR analysis. To facilitate end-use applications, SALP was encapsulated in poly(lactic acid)/poly(ethylene oxide) (PLA/PEO) nonwovens prepared by a free-surface electrospinning process. The release of SAL vapor from SALP-loaded nonwovens was studied using a citric acid (CA) solution of different concentrations. Additionally, a tri-layer nonwoven comprised of a SALP-loaded nonwoven sandwiched between two layers of CA-loaded fibers was developed. When exposed to 100 % RH, the composite nonwoven released SAL at a level of 0.046 ± 0.011 mg SAL/mg nonwoven in 4 h. The composite nonwoven exhibited antimicrobial properties against Escherichia coli K12, showing an 8-log reduction after a 4 h exposure to SAL vapor released from a 3 × 3 cm2 nonwoven. The antimicrobial nonwoven could be promising for limiting the proliferation of spoilage and pathogenic microorganisms to enhance the safety and reduce the wastage of food products.