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Acinetobacter baumannii is a significant pathogen of hospital-acquired infections, and its multidrug resistance (MDR) and extended drug resistance (XDR) have become increasingly severe, posing a global public health challenge. This article provides a narrative review of the major resistance mechanisms of Acinetobacter baumannii, including β-lactamase production, efflux pump overexpression, target site modification, reduced membrane permeability, and biofilm formation. Additionally, it summarizes the current main drugs and their target sites for treating MDR Acinetobacter baumannii infections, with a focus on the mechanism of action, antibacterial activity, and clinical research progress of the novel fully synthetic fluorocycline antibiotic—eravacycline. Eravacycline inhibits protein synthesis by high-affinity binding to the bacterial ribosomal 30S subunit and demonstrates activity against multidrug-resistant Acinetobacter baumannii (excluding Pseudomonas aeruginosa), providing a potential novel therapeutic option for MDR/XDR Acinetobacter baumannii infections. Finally, the article outlines future research directions and treatment strategies. Due to the narrative nature of this review, no systematic methodology (e.g., PRISMA) was applied, and the available clinical evidence, particularly for CRAB infections, remains limited. Full article

The innate immune response is a critical defense mechanism by which vertebrates recognize and eliminate invading pathogens. Pattern recognition receptors (PRRs) detect pathogen-associated molecular patterns and activate downstream signaling pathways. NOD1, a classic PRR of the NLR family, recruits the adaptor protein RIPK2 to initiate antibacterial signaling. In this study, we cloned and characterized the NOD1 gene from snakehead (Channa argus). Briefly, the full-length NOD1 cDNA is 2829 bp encoding 943 amino acids, showing high homology with Perciformes. The qPCR analysis revealed widespread NOD1 gene expression in various tissues, with significant upregulation in the gill (p < 0.05) and spleen (p < 0.05) following bacterial infection. Overexpression of the NOD1 gene activated the NF-κB signaling pathway in a dose- and time-dependent manner, and specifically responded to the bacterial ligand iE-DAP but not to other tested ligands. Furthermore, NOD1 synergized with the downstream adaptor RIPK2 to enhance NF-κB activity, and direct protein interaction between NOD1 and RIPK2 was confirmed by co-immunoprecipitation. Taken together, these findings demonstrate that snakehead NOD1 plays a critical role in the host antimicrobial immune response. Full article

Background/Objectives: Resistant pathogenic bacteria and fungi are a growing problem worldwide; therefore, the discovery of new active ingredients is an important challenge for which the functionalization of natural terpenes with biologically active heterocycles can provide a basis. To reach this goal, a series of 1,4-disubstituted-1,2,3-triazole conjugates was designed and synthesized starting from commercially available α-santonin. Methods: The key azido derivative intermediate was prepared according to literature procedures via Michael addition between dehydrosantonin and the TMSN₃/AcOH/Et₃N system at its highly reactive α-methylene-γ-lactone motif. Subsequently, the obtained azide was applied to regioselective Huisgen 1,3-dipolar cycloaddition reaction with a wide range of terminal alkynes bearing N-, S- and O-heterocycles. These include pyridine, pyrimidine, purine, quinoline, indol, or coumarin to afford the sesquiterpene–heterocycle chimaeras. All triazole conjugates were screened for in vitro antiproliferative activity by MTT assay against HeLa, MDA-MB231, SiHa, MCF-7 and A2780 human cancer cell lines compared with fibroblast cells (NIH/3T3) to check their cytotoxicity and antimicrobial effects on two Gram-positive (B. subtilis, S. aureus) pathogenic bacteria, two Gram-negative (E. coli and P. aeruginosa) pathogenic bacteria, and two yeasts (C. krusei and C. albicans). Results: The results indicated that most of the examined compounds expressed weak activity against human cell lines, while some of them showed moderate activity against S. aureus (up to 99% inhibition at 100 µg/mL conc.), C. krusei (up to 51% inhibition at 10 µg/mL conc.) and C. albicans (up to 52% inhibition at 10 µg/mL conc.). Conclusions: Further structural modification of the best, selective antibacterial and antifungal compounds may open the possibility to the development of effective natural sesquiterpene-based selective antimicrobial agents. Full article

(1) Background: The increasing antibiotic resistance of pathogens is necessitating new therapies that target virulence factors. Virulence factors include biofilm formation, which is a key pathogenic factor involved in bacterial pathogenicity and resistance. (2) Methods: Initially, biofilm formation assays were performed to screen the biofilm formation inhibition effects of gastrodin. A bacterial growth assay was performed to examine the synergistic effects and qRT-PCR was performed to identify the underlying molecular regulatory mechanisms. (3) Results: Gastrodin inhibits biofilm formation by bacteria such as E. faecalis (IC₅₀ = 1.56 μg/mL), E. faecium (IC₅₀ = 0.19 μg/mL), S. aureus (IC₅₀ = 6.25 μg/mL), C. acnes (IC₅₀ = 0.78 μg/mL), S. sobrinus (IC₅₀ = 12.5 μg/mL), P. aeruginosa (IC₅₀ = 25.00 μg/mL), and E. coli (IC₅₀ = 25. 10 μg/mL) without directly affecting bacterial growth, as shown by bacterial growth assay. Gastrodin also reduced the expression of cytolysin genes (cylLS, cylR2, and cylM), quorum sensing genes (fsrB, fsrC, gelE, ebpA, ebpB, acm, scm, and bps) and biofilm virulence genes (esp) as shown by qRT-PCR analysis and exhibited dramatic synergistic antibacterial effects in the growth assay. (4) Conclusions: These results suggest that gastrodin may be a promising novel antibacterial adjuvant for biofilm-related bacterial infections, but further experiments, including in vivo assays, are still needed. Full article

HP1090 is a short, cationic, amphipathic peptide derived from scorpion venom and previously described as a membrane-active antiviral compound. Here, we primarily characterize the antiviral activity of HP1090 and assess whether additional antibacterial effects are consistent with membrane-disruptive properties. Chemically synthesized HP1090 exhibited dose-dependent virucidal activity against multiple enveloped viruses, including herpes simplex virus type 1 and 2 (HSV-1, HSV-2), human immunodeficiency virus type 1 (HIV-1), and Zika virus (ZIKV), with IC₅₀ values ranging from 14.7 to 56.1 µg/mL. No activity was observed against the non-enveloped human rhinovirus 14 (HRV14), suggesting strict dependence on a viral lipid envelope. Consistent with a membrane-targeting mechanism, HP1090 induced rapid and concentration-dependent permeabilization of virus-like liposomes. HP1090 also displayed antibacterial activity against selected clinically relevant pathogens in agar-based growth inhibition assays. However, antibacterial effects required substantially higher concentrations (>125 µg/mL) and varied between bacterial species, with some strains showing little or no susceptibility. Membrane permeabilization assays in Listeria monocytogenes demonstrated disruption of bacterial membrane integrity as a contributing mechanism. No cytotoxicity was observed on mammalian cell lines at effective antiviral concentrations. Together, these findings establish HP1090 as a membrane-active venom peptide and, by linking envelope-dependent viral inactivation with bacterial membrane permeabilization, support a shared biophysical mode of action relevant to the development of membrane-targeting anti-infectives. Full article

Honeybee colonies are affected by bacterial, fungal, viral, microsporidian, and parasitic diseases that impair brood viability, adult survival, productivity, and beekeeping sustainability. Conventional control relies on sanitary measures, antibiotics where permitted, and synthetic acaricides, but these approaches are constrained by residues, resistance, regulation, and variable field performance. This narrative review critically evaluates essential oils as alternative or complementary tools against American foulbrood, European foulbrood, varroosis, nosemosis, chalkbrood, and mite-associated viral pressure. Evidence indicates that thymol, carvacrol, eugenol, cinnamaldehyde, and related constituents can show marked antibacterial, antifungal, acaricidal, antioxidant, and host-supportive activity under controlled conditions. However, most bacterial, fungal, and nosemosis data remain laboratory-based, and direct antiviral applications against honeybee viruses are not field validated. The strongest practical evidence concerns thymol-based control of Varroa destructor, where efficacy depends on formulation, release rate, temperature, colony status, and safety margins. Essential oils should therefore be considered components of integrated honeybee health management, not substitutes for established measures. Future studies should prioritize chemical standardization, dose–response testing, colony-level trials, brood and queen safety, sublethal behavior and physiology, gut microbiota, residues, and reproducible delivery systems. Full article

The copolymerization of biologically active N-(carboxyphenyl)maleimides with styrene was systematically investigated to elucidate the effect of positional isomerism (ortho-, meta-, and para-) on monomer reactivity and copolymer properties. Reactivity ratios (r₁, r₂) were determined using the Fineman–Ross method, and Q–e parameters were evaluated within the Alfrey–Price framework, revealing distinct electronic effects governing copolymerization behavior. Increasing the maleimide fraction in the feed resulted in decreased copolymer yield, intrinsic viscosity, molecular weight, and glass transition temperature, while all copolymers remained styrene-rich, indicating preferential styrene propagation. Comprehensive structural characterization (NMR, FTIR, and UV–Vis) confirmed successful incorporation of both monomer units. Rheological analysis demonstrated a clear viscosity trend (ortho > meta > para), highlighting the influence of substituent position on chain interactions and macromolecular architecture. Thermal analysis (TGA/DTA) showed good thermal stability up to 250–300 °C. Notably, the copolymers exhibited significant antibacterial and antifungal activity, with maximum inhibition observed against Candida albicans. This study establishes a direct correlation between substituent position and structure–property relationships, providing new insights for the rational design of functional styrenic copolymers with potential applications in antimicrobial and biomedical materials. Full article

Prolonged use of clear aligners promotes bacterial colonization and biofilm formation, which can compromise orthodontic outcomes. There is a clear clinical demand for approaches that can suppress pathogenic activity while preserving the fundamental functional and material characteristics of the aligners. To address this need, a novel strategy of fabricating metal–organic framework (MOF) coatings on aligners was adopted. Metal–organic frameworks (MOFs) have emerged as promising antibacterial coating materials by combining antimicrobial metal ions with biocompatible organic ligands. Three distinct porphyrin-based MOFs (Ag-, Cu-, and Ce-TCPP) were synthesized and fabricated as coatings on clear aligner surfaces via a coordination-driven self-assembly approach. The coated aligners were comprehensively assessed in vitro to determine their antibacterial performance, anti-inflammatory potential, biocompatibility, and key physical characteristics. Among the three coatings, Ag-TCPP showed the most favorable overall antibacterial and anti-biofilm performance in the present experimental system and facilitated macrophage polarization toward an anti-inflammatory M2-like phenotype. Ag-TCPP exhibited a significant inhibition zone of 6.75 ± 0.25 mm and reduced biofilm biomass by 72.2%. All MOF coatings exhibited excellent biocompatibility, and their application did not compromise the aligners’ mechanical integrity or aesthetic properties (light transmittance). This study reports the successful development of a novel metal–organic framework (MOF)-based coating strategy for clear aligners. Among the formulations investigated, the Ag-TCPP coating exhibited outstanding antibacterial and immunomodulatory performance while maintaining the critical mechanical integrity and aesthetic qualities of the aligner. The findings of this work offer a practical approach to designing multifunctional orthodontic devices that may reduce biofilm-related complications and improve clinical outcomes. Full article

Biosurfactants are surface-active microbial molecules with increasing industrial relevance as sustainable alternatives to synthetic surfactants. Among them, lipopeptides produced by Bacillus species, particularly surfactin, exhibit strong interfacial activity and biological functionality. In this study, rhizospheric soils from the La Araucanía region, Chile, were explored as a source of biosurfactant-producing bacteria. Eighteen strains were isolated, and two high-performing strains, Solo 1 and Solo 4, were identified as Bacillus amyloliquefaciens and Bacillus subtilis, respectively. Both strains harbored the srfAA gene and produced surfactin isoforms confirmed by MALDI-TOF MS. Kinetic analysis revealed distinct production profiles, with Solo 1 reaching a maximum of 90 mg L⁻¹ at 24 h, whereas Solo 4 showed continuous production up to 224.4 mg L⁻¹ at 72 h. Both biosurfactants exhibited high emulsification capacity (>80%) and stability across wide ranges of temperature, pH, and salinity. Importantly, cell-free supernatants from both strains showed antibacterial and antibiofilm activity against Staphylococcus aureus, with Solo 4 reaching 81% biofilm inhibition. In addition, surfactin-enriched extracts inhibited the pathogenic bacterium Pseudomonas syringae and the filamentous fungus Fusarium oxysporum, with Solo 4 consistently showing stronger antimicrobial performance. Overall, these findings identify Solo 4 as a promising native Bacillus strain for future development of biosurfactant-based systems aimed at antimicrobial control, biofilm management, agricultural pathogen suppression, surface sanitation, and environmentally compatible biotechnological processes. Full article

Urinary tract infections (UTIs) are commonly caused by bacteria that enter through the urethra and multiply in the bladder. The rising antibiotic resistance makes bacterial infections increasingly difficult to treat, necessitating the development of alternative solutions to combat resistant bacteria. The World Health Organization supports the integration of traditional medicine and medicinal plants into health systems, recognizing their therapeutic potential thanks to their active ingredients. In Cameroon, several medicinal plants are traditionally used to treat UTIs. However, information regarding this practice is poorly documented. In fact, systematic lists that would provide a thorough and organized understanding of the use of medicinal plants in treating UTIs are missing. Moreover, there is a lack of scientific evidence for the traditional use of medicinal plants in treating UTIs. This study aims to identify and document medicinal plants that are used to treat urinary tract infections at Dschang and evaluate the antibacterial activity of extracts from the most promising plants against selected bacteria that are responsible for urinary tract infections. The ethnobotanical study was conducted among herbalists, naturopaths, traditional healers and plant users through semi-structured interviews, and the plants listed were identified according to the literature information and at the National Herbarium of Cameroon. Extracts of the most cited plants (10) were obtained by maceration using water or a water–ethanol mixture (3:7; v/v). Then, the antibacterial activity of the as-prepared extracts was evaluated against five bacterial strains responsible for UTIs, such as Escherichia coli ATCC 25922, Staphylococcus aureus HM-468, Pseudomonas aeruginosa NR 48982, Klebsiella pneumoniae NCTCC-13810 and Klebsiella pneumoniae NR 41697, using the microdilution method. A total of forty-one (41) plant species belonging to 26 families were identified as plants used by the respondents to treat urinary tract infections in Dschang. Decoction, infusion and maceration were the most commonly used methods of plant preparation, whereas leaves, bark and fruits were the most used plant organs. From 20 plant extracts tested, the hydroethanolic extracts of Leucaena glauca and Lannea sp. revealed antibacterial activity with MICs ranging from 0.312 to 1.25 mg/mL. The MBC values obtained allowed us to conclude that these extracts exert a bactericidal effect. These results contribute to the identification of plants used to treat UTIs at Dschang and to validate the traditional use of Leucaena glauca and Lannea sp. in the treatment of urinary tract infections. Full article

The genus Capsicum is widely used worldwide for its culinary value and functional potential. The objective of this study was to evaluate the bioactive compounds, antioxidant and antimicrobial activity of sweet and hot pepper at different stages of ripeness. Six varieties of peppers at five stages of ripeness were analysed. Mineral parameters (Ca, Fe, Na, K, Mg) were determined by atomic absorption spectrophotometry, while bioactive compounds (vitamin C, organic acids, carotenoids, and phenols) were analysed by liquid chromatography. Antioxidant activity was evaluated using ABTS and DPPH assays, and antimicrobial activity was assessed by minimum inhibitory concentration against bacteria and yeasts. Multivariate analyses (PCA and heatmap) were carried out at a significance level of p < 0.05. The results showed that genotype was the main determinant of variability, surpassing the effect of ripeness. Potassium was the predominant mineral (3431.5 mg/100 g DW) in Malagueta chilli M5. Variety-specific peaks were identified, notably vitamin C in Habanero chilli (M3) (10,319.5 mg/100 g DW), capsaicin in Malagueta chilli (M5) (1949.8 mg/100 g DW), and carotenoids in Orange medium peppers (M5) (9495.8 mg/100 g DW). Antioxidant activity was higher in hot varieties (41.3 mmol ET/100 g DW in Habanero chilli (M2) by DPPH), while antimicrobial activity varied against Escherichia coli (2.6 mg/mL in Yellow medium peppers (M4)), Staphylococcus aureus (5.2 mg/mL in Orange medium pepper), and Streptococcus mutans (2.0 mg/mL in Jalapeño chilli), with low MIC values. Multivariate analyses confirmed that chemical and biological variability is primarily structured by genotype. Full article

This research is based on the eco-friendly biogenic synthesis of titanium dioxide (TiO₂) and manganese oxide (MnO) nanoparticles using Lawsonia inermis (henna) leaf extract. The biosynthesized NPs were examined via UV–visible spectroscopy, FTIR, FESEM, EDX, TGA, Zeta potential, and DLS to study their optical characteristics, functional group, structural nature, surface morphology, elemental composition, thermal stability, and surface charge. FTIR peaks confirmed the functional groups responsible for nanoparticle formation. FESEM micrographs indicated spherical TiO₂ nanoparticles and irregular MnO nanoparticles. The biosynthesized nanoparticles revealed antibacterial activity against pathogens, including Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Bacillus subtilis. Antioxidant potential was demonstrated using the DPPH assay, with MnO nanoparticles exhibiting higher activity (IC50: 30 µg/mL) than TiO₂ nanoparticles. Cytotoxicity studies on L929 cell lines revealed dose-dependent effects, while wound-healing assays indicated enhanced cell migration, particularly with MnO nanoparticles. This study highlights the L. inermis-mediated nanoparticles as sustainable and biocompatible with biomedical and environmental applications. Full article

Essential oils (EOs) from wild Calamintha nepeta (Portugal) populations collected in Portugal (Évora) were investigated in order to evaluate the impact of Mediterranean seasonal conditions on their phytochemical composition and biological activity. Essential oil GC-FID and GC-MS analyses revealed distinct seasonal chemotypes, with spring samples dominated by isopulegone/pulegone, whereas autumn samples contained higher proportions of isomenthone and menthol. Antioxidant activity was assessed through lipid peroxidation inhibition, DPPH radical scavenging and ferric reducing power assays, while antibacterial activity was evaluated against multidrug-resistant (MDR) clinical isolates. Seasonal differences were reflected in both EO chemical composition and bioactivity. Autumn samples displayed greater antioxidant potential, with Y1A showing the highest inhibition of lipid peroxidation (IC₅₀ = 0.85 mg/mL) and Y2A exhibiting the highest ferric reducing power. Conversely, spring samples were more active against MDR bacteria. Among them, Y1S showed the broadest antimicrobial spectrum, with MIC values ranging from 465 to 1767 μg/mL. The unusually wet spring season coincided with marked isopulegone accumulation (≈50%), while warmer autumn conditions favoured higher levels of isomenthone and menthol in the EOs. These findings highlight the importance of seasonal environmental conditions in determining the phytochemical profile and bioactive potential of C. nepeta EOs, providing valuable insights for their standardisation and valorisation in pharmaceutical, food and conservation-related applications. Full article

Chemical analysis of the marine-derived Saccharopolyspora sp. PG10 led to the isolation of a novel macrolactam, cebulactam A₃ (1), along with four known congeners, cebulactams A₁ and A₂ (2 and 3) and shengliangmycins B and D (4 and 5). The structure of 1 was established by high-resolution mass spectrometry (HRMS) and comprehensive nuclear magnetic resonance (NMR) analyses, and its absolute configuration was determined using Mosher’s method. Genome analysis identified a putative biosynthetic gene cluster consistent with a hybrid polyketide pathway. Antimicrobial evaluation revealed that shengliangmycin B exhibited the strongest activity, whereas cebulactam analogs exhibited weaker effects. These findings expand the structural diversity of cebulactam-type macrolactams and provide insights into their stereochemical variation. Full article

Background/Objectives: Antimicrobial resistance and bacterial persistence underscore the need to develop new chemotypes with multifunctional antibacterial mechanisms. This study aimed to design, synthesize, and evaluate curcumin-inspired 3,5-diarylidene-4-piperidones as versatile small molecules exhibiting antibacterial, antibiofilm, anti-efflux, DNA gyrase-inhibitory, and antiproliferative properties. Methods: A targeted series of triazole-conjugated 3,5-diarylidene-4-piperidones was synthesized through copper-catalyzed azide-alkyne cycloaddition click chemistry and subsequently characterized using standard spectroscopic techniques. The compounds were assessed for antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli. Selected active compounds underwent further evaluation for DNA gyrase inhibition, antibiofilm activity against multidrug-resistant S. aureus ATCC 33591, ethidium bromide accumulation, and antiproliferative effects on HCT116 and MCF7 cancer cells, with RPE1 cells serving as a control to evaluate cytotoxicity in normal cells. Additionally, computational studies, including QSAR analysis and molecular docking, were conducted to bolster structure–activity relationships and provide mechanistic insights. Results: Several derivatives demonstrated selective antibacterial activity against Gram-positive bacteria, particularly S. aureus, while exhibiting limited or no efficacy against E. coli. Compounds 7n and 7l emerged as the most potent against S. aureus, with minimum inhibitory concentrations (MICs) of 7.8 and 8.2 μM, respectively. Notably, compound 7l inhibited S. aureus DNA gyrase supercoiling, displaying an IC₅₀ of 3.20 μM, comparable to ciprofloxacin. Compound 7e exhibited the strongest antibiofilm activity against multidrug-resistant S. aureus, whereas compound 7a resulted in the highest accumulation of ethidium bromide, indicating robust anti-efflux activity. Antiproliferative assays revealed that select halogenated derivatives were effective against HCT116 and MCF7 cells, while the most promising antibacterial compounds exhibited minimal cytotoxicity toward RPE1 cells. Quantitative structure–activity relationship (QSAR) and docking studies supported the observed structure–activity relationships and suggested potential interactions with the ATPase binding site of DNA gyrase B. Conclusions: Triazole-conjugated 3,5-diarylidene-4-piperidones are promising multifunctional scaffolds with selective anti-S. aureus activity, antibiofilm and anti-efflux properties, and, for compound 7l, potent DNA gyrase inhibition. These findings support further optimization of this chemotype as a platform for developing antibacterial agents with polymechanistic activity. Full article