Search Results (4,288)

The misuse of antibacterial agents has contributed to the growing prevalence of antibiotic resistance, highlighting an urgent need to explore alternative anti-infection therapeutic strategies. Antimicrobial peptides (AMPs) are naturally occurring molecules. They exhibit broad-spectrum antimicrobial activity and represent promising candidates for the development of novel therapeutics. A cysteine-rich antimicrobial peptide was identified and characterized from the genome of Tigriopus japonicus and designated “TjRcys1”. The precursor form of TjRcys1 comprises 96 amino acids. Structural analyses of TjRcys1 revealed random coils, two α-helices, and two β-strands. Recombinant TjRcys1 had inhibitory effects upon Staphylococcus aureus and Bacillus sp. T2, with a minimum inhibitory concentration of 64 μM for both. TjRcys1 did not show complete inhibition against Vibrio alginolyticus, Klebsiella pneumoniae, or Aeromonas hydrophila at 64 μM, but it did slow their growth rate. TjRcys1 could disrupt the permeability of the cell membrane of S. aureus. Transcriptomic analyses indicated that TjRcys1 could interfere with the ribosome biosynthesis and nucleotide metabolism of K. pneumoniae. Our results provide a valuable reference for the development of new AMPs and optimization of their design. Full article

Due to the heightened flood risk resulting from climate change, innovative and advanced green building materials are required to enhance the durability and biological resistance of concrete structures exposed to persistent moisture. This study investigates the use of nanosilver-enriched plasticizers as a novel modification of concrete for applications in flood-prone environments. The findings demonstrate that the incorporation of nanosilver enhances the mechanical strength of concrete by reducing surface tension and porosity, thereby enhancing durability and extending service life. Moreover, nanosilver-modified concrete exhibits significant antimicrobial activity, effectively limiting microbial-induced corrosion. Preliminary microbiological analyses showed a reduction of sulfur-oxidizing bacteria (SOB) and sulfate-reducing bacteria (SRB) by 85–92%, as well as a decrease of over 80% in potentially pathogenic microbial genera. This study also highlights the importance of skilled labor and adequate training to ensure the responsible implementation of nanosilver-based technologies in sustainable construction. Overall, nanosilver-enriched plasticizers represent an innovative green building material that supports flood-resilient, durable, and sustainable concrete construction. Full article

Background/Objectives: Infections due to multidrug-resistant (MDR) Acinetobacter baumannii represent a critical challenge in modern healthcare, with limited therapeutic options. Eravacycline, a novel fluorocycline antibiotic, demonstrates promising in vitro activity, but real-world clinical data for complex intra-abdominal infections (IAIs) are scarce. We present two cases of severe IAI caused by carbapenem-resistant A. baumannii (CRAB) successfully treated with eravacycline. Methods: We describe the clinical course, microbiological findings, and outcomes of two critically ill patients. Case 1 was a 75-year-old male with biliary peritonitis following an endoscopic procedure. Case 2 was a 64-year-old male with infected pancreatic walled-off necrosis. Both patients had cultures positive for CRAB and failed multiple prior antibiotic regimens. Results: In both cases, the initiation of intravenous eravacycline led to significant clinical improvement, including resolution of septic shock and defervescence. A marked reduction in inflammatory markers (C-reactive protein and procalcitonin) was observed, alongside microbiological clearance of CRAB. Eravacycline was well tolerated, with no significant adverse events. Conclusions: These case reports suggest that eravacycline can be an effective and safe salvage therapy for complex IAIs caused by CRAB, even in scenarios of partial source control. It represents a valuable addition to the antimicrobial armamentarium for managing infections caused by these extensively drug-resistant organisms. Full article

Dental caries is a multifactorial chronic infectious disease that impacts healthcare costs globally, caused by alterations of the plaque microbiome and proliferation of cariogenic Streptococcus mutans. Treatments targeting S. mutans, such as alternative strategies using probiotics, might be effective in preventing the development of dental caries. In this study, the probiotic formulation of Lactobacillus reuteri SGL01, vitamin C, and acerola was tested against S. mutans DSM20523. Antimicrobial activity was assessed by deferred antagonism and spot-on-lawn assays for L. reuteri SGL01. MIC and MBC of L. reuteri SGL01 cell-free supernatant (CFS), vitamin C, and acerola were determined with the microdilution method. Time–kill assays determined the bactericidal kinetics for each compound. The checkerboard method was used to evaluate the potential synergistic activity of CFS–vitamin C or CFS–acerola at scalar dilutions from 1 to 8X MIC. Lastly, antibiofilm activity was tested for each compound. Antimicrobial activity of L. reuteri SGL01 was first assessed by classic methods. MIC and MBC values differed for one dilution for all compounds, with values of 25% and 50% for CFS, 9.3 mg/mL and 18.7 mg/mL for vitamin C, and 18.7 mg/mL and 37.5 mg/mL for acerola, respectively. Moreover, time–kill assays confirmed the bactericidal activity at different timepoints: 4 h for CFS, 6 h for vitamin C, and 24 h for acerola. The fractional inhibitory concentration index (FICI) showed indifference for all combinations, and for associations tested at 2, 4, and 8XMIC. S. mutans biofilm production was impaired for all components, with stronger activity by vitamin C and acerola at lower concentrations. The probiotic formulation containing L. reuteri SGl01, vitamin C, and acerola extract exerts a bactericidal effect, especially strong for the CFS, as well as antibiofilm activity. Thus, the combination of these three components could be advantageous for their complementary effects, with use as a novel treatment against the development of dental caries by S. mutans. Full article

Drug-resistant bacteria cause millions of global infections each year, and the development of alternative antimicrobial drugs has become a serious undertaking. Currently, peptides with antimicrobial activity represent potential candidates for new antibiotic discovery as they are less likely to cause drug resistance in bacteria. In this study, bifunctional peptides with potent trypsin-inhibitory activity and antimicrobial activity were obtained by rational computation-based structural modifications to a novel Bowman–Birk-type inhibitor (BBI) peptide. The analogues not only displayed potent bacterial killing ability against two drug-resistant bacteria strains of E. coli but also an excellent safety profile, as assessed by low haemolytic activity and low anti-proliferation activity on HaCaT cells. Throughout the molecular dynamics simulations, the peptides exhibited stable adsorption onto the mixed POPE/POPG membrane; most amino acid residues of the AMPs remained bound to the membrane surface, with a few amino acid residues partially penetrating the membrane interior. This showed that the electrostatic interactions were the dominant driving force mediating the peptide–membrane associations. In addition, the tested peptides displayed a degree of stability in the presence of salt ions, serum, and trypsin. These modified peptides thus possess potential as clinical antibacterial agents, and the strategies used in structural modification may also provide a different path to developing new antimicrobial peptides. Full article

The growing threat of antibiotic-resistant bacteria necessitates the development of alternative antimicrobial strategies. This study investigated the design and evaluation of novel photodynamic agents based on Rose Bengal (RB) conjugated to two plant lectins, Pisum sativum agglutinin (PSA) and Laburnum anagyroides agglutinin (LABA), for targeted photodynamic inactivation of Gram-positive and Gram-negative bacteria. Both conjugates demonstrated high singlet oxygen quantum yields compared with free RB. Antibacterial efficacy was assessed against methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Salmonella paratyphi B under white LED illumination. PSA-RB exhibited superior bactericidal activity against all strains, whereas LABA-RB showed strain-specific efficacy, particularly against Gram-negative species. A binary mixture of PSA-RB and LABA-RB synergistically inactivated both MSSA and MRSA at RB concentrations of 6–10 nM and light doses of 3.1–7.8 J/cm². Complete killing of E. coli and S. paratyphi B was achieved at approximately half the RB concentrations needed for individual conjugates. PSA-RB activity primarily drove the inactivation of P. aeruginosa. Uptake studies revealed significantly enhanced accumulation of lectin-conjugated RB compared to free RB, with synergistic uptake observed for the conjugate mixture. These results suggest that lectin-based RB conjugates are effective antibacterial agents for photodynamic treatment, especially via the dual-targeting method. Full article

Microbial biosurfactants (mBSs) are bioactive molecules with diverse applications, notably as antimicrobial agents against antibiotic-resistant pathogens. Produced by bacteria and yeasts, mBSs are classified as glycolipids, lipopeptides, polymeric, and particulate types. The global rise in multidrug-resistant organisms, such as Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium, Pseudomonas aeruginosa, and Acinetobacter baumannii, underscores the urgent need for new antimicrobial strategies. mBSs disrupt microbial growth by interacting with the lipid components of pathogens, offering promising alternatives to conventional antibiotics. This review highlights the sources, chemical structures, and properties of mBSs, their antimicrobial activities, synergistic effects with antibiotics, and structure–activity relationships. Special emphasis is placed on surfactant modification, where targeted changes—such as valine substitution in surfactin—significantly lower critical micelle concentrations (CMC) and enhance antimicrobial potency. Such rational engineering demonstrates how biosurfactants can be tailored for improved biomedical performance while minimizing cytotoxicity. In parallel, artificial intelligence (AI) algorithms, including artificial neural networks and genetic algorithms, optimize yields, predict substrate suitability from agricultural residues, and guide microbial strain engineering. AI models can predict interfacial behavior and synchronize fermentation with purification. Advancing the understanding of mBS interactions with microbial membranes, combined with modification strategies and AI-guided optimization, is essential for developing targeted therapies against resistant infections. Future research should integrate these approaches to engineer novel derivatives, reduce costs, and validate clinical potential through comprehensive in vivo studies. Full article

Pseudomonas aeruginosa is a resilient Gram-negative pathogen frequently implicated in healthcare associated infections, particularly among immunocompromised individuals and those with chronic conditions such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), or cancer. It is well known for its high resistance to antibiotic treatment. This review briefly mentions P. aeruginosa’s resistance mechanisms, biofilm formation, and virulence factors, while primarily focusing on treatment challenges and recent advancements in therapeutic strategies aimed at overcoming resistance. Covered are novel non-antibiotic interventions such as quorum sensing inhibitors, quorum quenching agents, iron chelators, lectin and efflux pump inhibitors, as well as antimicrobial peptides and nanoparticles. Traditional medicine, phytochemicals, and probiotics are also evaluated. Additionally, this review explores the development of a viable vaccine, bacteriophage therapy, lactoferrin-hypothiocyanite combination, and topical use of electrochemical scaffolds. This review emphasizes the need for extensive safety studies and in vivo validation of these emerging non-antibiotic therapeutic strategies to determine their efficacy, pharmacological behavior, and clinical feasibility before they can be translated into practice. Many of these emerging treatments could play a vital role in future combination therapies by enhancing the efficacy of existing antibiotics and countering resistance and virulence mechanisms. Advancing these approaches from laboratory to clinical application remains a major challenge, making the development of approved therapies or vaccines a critical scientific and public health priority. Full article

Multidrug resistance (MDR) in Gram-negative bacteria is a global issue and needs to be addressed urgently. MDR can emerge through genetic mutations and horizontal gene transfer and deteriorate under antibiotic selective pressure. The emergence of resistance to last-resort antibiotics, which are used to treat MDR bacteria, is of particular concern. Colistin has been recognized as a last-line antibiotic for the treatment of MDR Gram-negative bacterial infections caused by Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Recently, the increasing reports of colistin resistance pose a significant threat to public health, caused by both acquired and intrinsic mechanisms. The review aimed to elucidate the trends in colistin resistance, the use of colistin in human and veterinary medicine, underlying resistance mechanisms and transmission pathways, and potential mitigation of this emerging threat through novel intervention strategies. Colistin resistance is mediated by plasmid-encoded phosphoethanolamine transferases (mcr-1 to mcr-10) and chromosomal lipid A remodeling pathways. In Escherichia coli, resistance involves mcr-1–10, acrB efflux mutations, pmrA/pmrB, arnBCADTEF, and mgrB inactivation. Klebsiella pneumoniae exhibits mcr-1, mcr-8, mcr-9, mgrB disruption and phoP/phoQ–pmrAB activation. Acinetobacter baumannii harbors mcr-1–4, while Salmonella enterica and Enterobacter spp. carry mcr variants with arnBCADTEF induction. Therapeutic options include adjunct strategies such as antimicrobial peptides, nanomaterials, therapeutic adjuvants, CRISPR-Cas9-based gene editing, probiotics, vaccines, and immune modulators to restore susceptibility. This review identified that specific and wide actions are required to handle the growing colistin resistance, including genomic surveillance, tracing novel resistance mechanisms, and the application of alternative management strategies. The One Health approach is considered a key strategy to address this growing issue. Full article

This study aimed to investigate the chemical composition and biological potential of needle extracts from five pine species, including antimicrobial, antioxidant, and cytotoxic activity, as well as their influence on cell cycle progression. Needle extracts were prepared using three extraction methods: conventional maceration (CM), ultrasound-assisted extraction (UAE), and digestion (D). The chemical profile was determined with an emphasis on phenolic acids, flavonoids, and related phenolic compounds. The highest total phenolic content was observed in Pinus sylvestris (3.438 mg/g GAE), followed by Pinus heldreichii (2.732 mg/g GAE). Rutin, ferulic acid, and quercitrin were identified as the predominant phenolic compounds. The highest total flavonoid content was found in Pinus pinea extracts obtained by digestion (1.213 mg/g QE), followed by P. heldreichii (1.074 mg/g QE) and Pinus halepensis (1.074 mg/g QE), both obtained by UAE. Among all examined species, Pinus pinea exhibited the highest TTC values, regardless of the extraction method (7.31–8.21 mg/g GAE). Antibacterial testing showed that P. pinea had an MIC of 19 mg/mL against Enterococcus faecium, while P. sylvestris had the same MIC against Bacillus spizizenii. All extracts exhibited cytotoxic effects using MTT assay against HeLa cells at concentrations of 8%, 16%, and 32%, while LS 174T cells were the least sensitive. Pine needle extracts from Montenegro are a valuable source of phenolic and flavonoid compounds, and they demonstrate antimicrobial and cytotoxic activities. The results support the need for further in vivo studies and elucidation of mechanisms of action in order to assess their potential application as novel bioactive agents. Full article

Alicyclobacillus acidoterrestris is an acidothermophilic bacterium considered a significant challenge to the food industry, particularly in the production of fruit juices and concentrates. Its ability to survive pasteurization and form spores and biofilms makes it a persistent contaminant that can spoil products and generate off-flavors even during product storage. Recent studies have increasingly focused on developing new strategies to eliminate both vegetative cells and biofilms, with special attention on natural compounds such as plant extracts, essential oils and antimicrobial metabolites. These natural agents offer promising alternatives for controlling A. acidoterrestris and might contribute to improvement in safety and quality of juice products. This article presents a comprehensive overview of current strategies for controlling Alicyclobacillus species in food processing environments, with an emphasis on A. acidoterrestris as a major spoilage organism in the fruit juice industry. It summarizes the established physical and chemical control methods, as well as highlights emerging novel approaches involving natural-origin antimicrobial compounds considered useful for mitigating Alicyclobacillus contamination. Full article

Lactic acid bacteria (LAB), as the core microorganisms in silage fermentation, play a crucial role in improving silage quality and ensuring feed safety, making the screening, identification, and functional characterization of LAB strains a significant research focus. Researchers initially isolate and purify LAB from various samples, followed by identification through a combination of morphological, physiological, biochemical, and molecular biological methods. Systematic screening has been conducted to identify LAB strains tolerant to extreme environments (e.g., low temperature, high temperature, high salinity) and those possessing functional traits such as antimicrobial activity, antioxidant capacity, production of feruloyl esterase and bacteriocins, as well as cellulose degradation, yielding a series of notable findings. Furthermore, modern technologies, including microbiomics, metabolomics, metagenomics, and transcriptomics, have been employed to analyze the structure and functional potential of microbial communities, as well as metabolic dynamics during the ensiling process. The addition of superior LAB inoculants not only facilitates rapid acidification to reduce nutrient loss, inhibit harmful microorganisms, and improve fermentation quality and palatability but also demonstrates potential functions such as degrading mycotoxins, adsorbing heavy metals, and reducing methane emissions. However, its application efficacy is directly constrained by factors such as strain-crop specific interactions, high dependence on raw material conditions, limited functionality of bacterial strains, and relatively high application costs. In summary, the integration of multi-omics technologies with traditional methods, along with in-depth exploration of novel resources like phyllosphere endophytic LAB, will provide new directions for developing efficient and targeted LAB inoculants for silage. Full article

Mammarenaviruses (MaAv) cause persistent infection in their natural rodent hosts across the world and, via zoonotic events, can cause severe disease in humans. Thus, the MaAv Lassa virus (LASV) in Western Africa and the Junin virus (JUNV) in the Argentinean Pampas cause hemorrhagic fever diseases with significant case fatality rates in their endemic regions. In addition, the globally distributed MaAv lymphocytic choriomeningitis virus (LCMV) is an underrecognized human pathogen of clinical significance capable of causing devastating infections in neonates and immunocompromised individuals. Despite their impact on human health, there are currently no FDA-approved vaccines or specific antiviral treatments for MaAv infections. Existing anti-MaAv therapies are limited to the off-label use of ribavirin, whose efficacy remains controversial; hence, the development of novel therapeutics to combat human pathogenic MaAv is vital. We employed a high-throughput cell-based infection assay to screen the Pandemic Response Box, a collection of 400 diverse compounds with established antimicrobial activity, for MaAv inhibitors. We identified Ro-24-7429, an antagonist of the HIV-1 Tat protein and RUNX family transcription factor 1 inhibitor; WO 2006118607 A2, a dihydroorotate dehydrogenase inhibitor; and verdinexor, a novel selective inhibitor of nuclear export (SINE) targeting the XPO1/CRM1, as potent anti-MaAv compounds. Consistent with their distinct validated targets, verdinexor and WO 2006118607 A2 exhibited very strong synergistic antiviral activity when used in combination therapy. Our findings pave the way for the development of verdinexor as a potent host-directed antiviral against MaAv, which could be integrated into the development of combination therapy with direct- or host-acting antivirals to combat human pathogenic MaAv. Full article

Schiff bases are bioactive compounds that have been synthesized by many researchers in recent years. They may also exhibit strong antimicrobial activities against various pathogenic microorganisms in both medicine and veterinary applications. The synthesis of new Schiff base-derived compounds remains of interest due to the increasing problem of antibiotic-resistance in clinical practice. Seven new Schiff base derivatives were synthesized, and their chemical structures were characterized using FT-IR, ¹H/¹³C NMR, and LCMS-MS analyses. The antimicrobial activities of thesyntesized compounds against various pathogenic bacteria, yeasts, and fungi were evaluated using the disk-diffusion method, and their MIC values were also determined. In addition, one representative microorganisms from each class were selected for molecular docking studies. IFD analyses were performed for the 4f and 4g ligands using the dihydrofolate reductase enzyme. Spectroscopic analyses confirmed the structures of the synthesized compounds, revealing the presence of characteristic imine functionalities and validating the integrity of the molecular frameworks. Antimicrobial assays demonstrated that several derivatives exhibited measurable activity, with compounds 4f and 4g showing the most potent effects, displaying MIC values of 32 µg/mL against B. cereus and E. faecalis, respectively. Molecular docking studies further indicated that both 4f and 4g bind efficiently to the DHFR active site. These findings indicate that among the synthesized Schiff base derivatives, compounds 4f and 4g exhibit particularly promising antimicrobial activity, warranting further pharmacological evaluation and medicinal chemistry optimization. Full article

Bovine Respiratory Disease (BRD) represents one of the largest causes of economic loss and animal morbidity in the global cattle industry, second only to neonatal diarrhea. Its etiology is complex, originating from a multifactorial combination of host susceptibility, environmental stressors, viral infections, and secondary bacterial pathogens. Although viruses are often the initial cause of disease, suppressing the host’s respiratory defense mechanisms, most of the severe pneumonic damage and clinical signs can be attributed to bacterial infections. This review provides an overview of the primary bacterial agents identified within the BRD complex, including Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. We discuss their role as commensals that then become opportunistic pathogens, and further how they interact in a synergistic relationship with a primary viral insult, leading to the resulting pathogenesis and the development of pneumonia. This manuscript discusses in further detail some of the challenges in BRD management, such as the limitations of current diagnostic methodologies, overreliance on antimicrobial therapy, and the growing concern of antimicrobial resistance. Lastly, the need for integrated approaches in management, better husbandry and biosecurity, coupled with the development of novel therapeutic alternatives, is underlined as a means of assuring a sustainable control of this serious syndrome. Full article