Secondary metabolites (a.k.a. natural products) are believed to play beneficial roles for the producing organisms, such as coping with environmental stress or outcompeting other organisms. Some of them may function as signals. One such class of natural products is the cyclitol/aminocyclitol family of compounds, which includes myo-inositol and its derivatives, the aminoglycoside antibiotics, and the C7-cyclitols and C7N-aminocyclitols. While the function of inositol and its derivatives as intracellular signaling molecules has been well established, more recent studies have also demonstrated their important ecological roles. Studies have also shown that aminoglycoside antibiotics may function as signals that regulate biofilm formation in bacteria and secondary metabolite production in fungi. Several C7-cyclitols and C7N-aminocyclitols, e.g., acarbose, validamycin, and kirkamide, have been associated with gut microbiota modulation, gene regulation in fungi and insects, and/or plant-bacteria endosymbiosis. While mycosporine-like amino acids (MAAs) are well known for their UV-protective activities, studies with human cells and animals have shown intriguing biological activities involving gene regulation and activation of signaling pathways. This article reviews the roles of this family of natural products as signaling molecules involved in various biological events, including bacterial colonization and gene regulation, with physiological and ecological implications that may affect human health and other organisms.

Introduction: Acute Kidney Injury (AKI) is frequently encountered among critically ill hospitalised children treated with Aminoglycosides (AGs). However, data regarding noncritically ill hospitalised children treated with AGs is lacking in the literature. Aim: To evaluate the occurrence of AKI among non-critically ill hospitalised children treated with AGs. Materials and Methods: The present prospective observational study was conducted in the Departments of Paediatrics and Paediatric Nephrology at the Government Medical College Srinagar, Jammu and Kashmir, India, from October 2018 to September 2020, on 142 children aged between one month and 18 years. These patients had normal renal function at admission and received at least one AG as in-hospital treatment for five days or longer. The rate of occurrence of AKI in the present study was evaluated using the paediatric Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (pRIFLE) and Acute Kidney Injury Network (AKIN) criteria. Frequency and percentage were calculated for qualitative variables, while the relationship between variables was analysed using the Student’s t-test and Chi-square test. Results: Out of 142 children studied, 78 (54.92%) were males. Glomerular Filtration Rate (GFR) was estimated using the Schwartz formula, wherein 29 (20.4%) patients had AKI by AKIN criteria and 36 (25.3%) patients had AKI by pRIFLE criteria. The children with AKI were younger (mean age 23.8 months). Compared to a 12-hour AG dosing interval, patients who received a 24-hour dosing interval had a significantly lower rate of AKI (p<0.05). Conclusion: A substantial proportion of non-critically ill young children receiving daily multiple doses of AGs for five days or longer developed AKI.

Herein, we demonstrated the formation of a biocompatible hydrogel using a novel dipeptide, H-Glu-Ala-OH (or EA), for the first time. The isomeric chloro-cinnamoyl moieties (shortened as 2ClCA and 4ClCA) were attached to the N-terminal of EA to fabricate the gelators 2ClCA-EA and 4ClCA-EA. Only 2ClCA-EA formed a stable translucent hydrogel, suggesting its remarkable regioisomer-specific hydrogelation phenomena. The hydrogels of 2ClCA-EA, comprising high aspect ratio nanofibers, displayed self-healing, injectable, and moldable properties. Spectroscopic data suggested concentration-triggered chiroptical alteration in the hierarchical aggregates of 2ClCA-EA and 4ClCA-EA. X-ray diffraction and computational studies revealed the formation of a highly ordered tilted lamellar organization of both 2ClCA-EA and 4ClCA-EA during self-assembly. Being biocompatible, the hydrogel of 2ClCA-EA was utilized for the efficient attachment of WI38 cells. Meanwhile, streptomycin, an aminoglycoside antibiotic, was encapsulated in the hydrogel matrix. Surprisingly, the antibiotic-loaded hydrogel showed superior mechanical properties due to the enhanced physical cross-linking between the gelator and streptomycin. The drug-loaded hydrogel showed efficient antibacterial properties. Finally, in vivo experiments on bacteria-infected mice demonstrated the remarkable topical wound-healing potential of the drug-loaded hydrogel.

Background/Objectives: Gentamicin (GEN) is an aminoglycoside antibiotic used in veterinary medicine to treat infections caused mainly by Gram-negative bacteria. GEN is a mixture of pharmacologically active components, known as isoforms. The objective was to develop and validate a sensitive, accurate, and precise Ultra-Performance Liquid Chromatography with triple quadrupole mass detector (UPLC-MS/MS) method to quantify the different GEN isoforms in pig plasma and feces using streptomycin as an internal standard. Methods: Solid-phase extraction (SPE) was carried out. A high-strength silica (50 × 2.1 mm, 1.8 µm) column was used for chromatographic separation and a mobile phase of 0.26% HFBA in water (A) and acetonitrile (B) was delivered in a gradient with a flow rate of 0.5 mL/min. The column temperature was 40 °C and the sample injection volume was 30 µL. Results: The method showed good selectivity and specificity, with no interfering peaks. Calibration curves were linear in the range from 0.05 to 0.3 µg/mL for all isoforms in both matrices. Within- and between-run precision and accuracy were satisfactory for the lower limit of quantification (LLOQ), with coefficients of variation (CV) ≤ 13.4% and deviations ≤ 116.5% in plasma and CV ≤ 12.3% with deviations ≤ 101.7% in feces. No carry-over was observed, and analyte stability was confirmed under different storage conditions. Conclusions: The method development fulfilled all validation criteria established by the European Medicine Agency Guideline (EMA/CHMP/ICH/172948/2019). Moreover, the applicability of the method in clinical practice was demonstrated by the quantification of GEN in plasma and feces samples from pigs.

Potato common scab, incited by pathogenic Streptomyces species, poses a significant threat to agriculture. The biocontrol agent Streptomyces sp. strain PBSH9 has shown remarkable field efficacy, yet its underlying antibacterial mechanisms remain unclear. To bridge this knowledge gap, we employed an integrated transcriptomic, proteomic, and metabolomic approach to compare PBSH9 under high (8-day) and low (2-day) antibacterial activity conditions. Transcriptomics identified 2,653 differentially expressed genes (DEGs), primarily enriched in oxidative phosphorylation and β-lactam resistance pathways. Proteomics quantified 32 differentially abundant proteins (DAPs), which were also predominantly involved in energy metabolism. Critically, metabolomic profiling of 1,299 differential metabolites (DAMs) revealed the core of the antibacterial activity: a massive > 28-fold accumulation of the antibiotics L-anticapsin and bacilysin, coupled with a significant 1.08- to 2.85-fold increase in several aminoglycoside antibiotics, including neomycin B and kanamycin. This enhanced antibiotic production was supported by the systematic upregulation of energy metabolism pathways, such as oxidative phosphorylation and the TCA cycle. Multi-dimensional correlation networks linked antibiotic accumulation to DEGs (st, phzF) and DAPs. Our findings demonstrate that the potent biocontrol activity of PBSH9 stems from a metabolic reprogramming that fuels the synergistic accumulation of a diverse antibiotic arsenal. This study provides a comprehensive molecular blueprint for optimizing and engineering this promising biocontrol strain.

Gentamicin, a widely used aminoglycoside antibiotic, is associated with cardiotoxic effects largely mediated by oxidative stress and lipid metabolic disturbances. This study evaluated the cardioprotective potential of methanolic stem bark extract of Vitex doniana (MSEVD) against gentamicin-induced cardiac injury in Wistar rats. Thirty-six female rats were divided into six groups and treated for 12 days with normal saline, gentamicin (100 mg/kg), gentamicin plus graded doses of MSEVD (100, 200, and 400 mg/kg), or gentamicin plus silymarin (75 mg/kg) used as a positive control. Serum lipid profile parameters (TC, TG, HDL-c, LDL-c, VLDL-c) and atherogenic index (AI) were evaluated, alongside histopathological examination of heart tissues. Gentamicin administration significantly increased TC, TG, LDL-c, and AI, while reducing HDL-c, indicating marked dyslipidaemia and elevated cardiovascular risk. Co-administration of MSEVD significantly ameliorated these alterations in a dose-dependent manner, with the 400 mg/kg dose showing near-complete normalization of lipid indices and superior reduction in VLDL-c compared with the reference drug. Histopathological findings corroborated the biochemical results, showing severe myocardial degeneration, necrosis, inflammation, and vascular damage in gentamicin-treated rats, while MSEVD markedly preserved myocardial architecture, particularly at higher doses. These findings demonstrate that methanolic stem bark extract of Vitex doniana exerts significant cardioprotective and hypolipidaemic effects against gentamicin-induced cardiac injury, likely mediated through its antioxidant and anti-inflammatory phytoconstituents, supporting its potential as a natural therapeutic agent in drug-induced cardiotoxicity.

Enrichment and analysis of aminoglycoside antibiotics in honey using hydrophilic magnetic graphene composites combined with high performance liquid chromatography mass spectrometry

Antibiotic-tolerant bacteria, due to their unique physiology, are refractory to antimicrobial killing and pose challenges for infection control. Incomplete knowledge of how bactericidal antibiotics work limits our understanding of partial resistance due to phenotypic tolerance in mycobacteria, a driver for developing genetic resistance. Using proteomics, 13C isotopomer analysis, genetic and biochemical assays, we investigated the physiological response of M. smegmatis challenged with aminoglycoside and fluoroquinolone antibiotics. Two distinct classes of antibiotics elicited remarkably similar responses and increased flux through the TCA cycle, causing enhanced respiration, ROS generation, and ATP burst. We observed that excessive ATP levels and not ROS dominantly contribute to cidality, which may in part be conferred by sequestration of divalent metal ions by ATP. Consequently, 13C isotope tracing indicated TCA cycle flux deviation from its oxidative arm as a bacterial adaptive mechanism, which also included activated intrinsic resistance and a higher propensity to develop antibiotic resistance. Our study provides a new understanding of the intricate mechanisms of antibiotic-induced cell death and expands the current paradigm for antibiotic action.

Antibiotic-tolerant bacteria, due to their unique physiology, are refractory to antimicrobial killing and pose challenges for infection control. Incomplete knowledge of how bactericidal antibiotics work limits our understanding of partial resistance due to phenotypic tolerance in mycobacteria, a driver for developing genetic resistance. Using proteomics, 13C isotopomer analysis, genetic and biochemical assays, we investigated the physiological response of M. smegmatis challenged with aminoglycoside and fluoroquinolone antibiotics. Two distinct classes of antibiotics elicited remarkably similar responses and increased flux through the TCA cycle, causing enhanced respiration, ROS generation, and ATP burst. We observed that excessive ATP levels and not ROS dominantly contribute to cidality, which may in part be conferred by sequestration of divalent metal ions by ATP. Consequently, 13C isotope tracing indicated TCA cycle flux deviation from its oxidative arm as a bacterial adaptive mechanism, which also included activated intrinsic resistance and a higher propensity to develop antibiotic resistance. Our study provides a new understanding of the intricate mechanisms of antibiotic-induced cell death and expands the current paradigm for antibiotic action.

Establishment of a human inner ear model reveals that gentamicin C2b is substantially less ototoxic than clinical gentamicin.

c-di-GMP regulates the resistance of Pseudomonas aeruginosa to heat shock and aminoglycoside antibiotics by targeting the σ factor RpoH.

Multi-scale quality evaluation and geographical origins discrimination of Ankang green tea by intelligent sensory analysis, selenium elemental analysis and quantitative non-volatile sensometabolomics.

Gentamicin (GTC) is a widely used aminoglycoside antibiotic, but its therapeutic application is limited by nephrotoxic and hepatotoxic effects primarily driven by oxidative stress. This study investigated the potential protective role of cranberry (CRB) (Vaccinium macrocarpon), known for its antioxidant and anti-inflammatory properties, against GTC-induced nephrotoxicity in rats. Hepatic biochemical and histopathological parameters were also evaluated as supportive markers of systemic toxicity. Thirty-two rats were divided into four groups: Control, CRB, GTC + CRB, and GTC. GTC (80 mg/kg, s.c.) and CRB (200 mg/kg, p.o.) were administered for seven consecutive days. Biochemical analyses showed significant increases in serum BUN, urea, creatinine, ALT, and AST levels in the GTC group, confirming renal and hepatic impairment. Co-treatment with CRB reduced these elevations and improved antioxidant parameters, reflected by decreased MDA and oxidative stress index levels and increased total and native thiols (p < 0.001). Gene expression analyses demonstrated that GTC upregulated pro-apoptotic genes (Bax, caspase-3, -9) and downregulated the anti-apoptotic Bcl-2, whereas CRB co-administration reversed these alterations. Histopathological evaluations supported the biochemical findings, revealing severe tubular and hepatocellular necrosis, inflammatory infiltration, and hemorrhage in the GTC group, which were markedly alleviated by CRB supplementation. These results suggest that CRB may exert a partial renoprotective effect against GTC-induced oxidative and apoptotic damage, possibly through its antioxidant and cytoprotective properties.

This study aimed to isolate and characterize bacteriophages infecting Chryseobacterium sp., an opportunistic pathogen responsible for considerable mortality in rainbow trout (Oncorhynchus mykiss Walbaum, 1792) aquaculture. Chryseobacterium isolates were recovered from diseased trout collected from aquaculture facilities in Mersin and Van (Türkiye) using Anacker–Ordal medium. Identification was performed through API 20E/20ZYM biochemical profiling and 16S rRNA gene sequencing. Antibiotic susceptibility was evaluated by the Kirby–Bauer disk diffusion method following CLSI and EUCAST guidelines. Phages were isolated from water samples via 0.22 μm filtration and purified using the double-layer agar method. Antimicrobial susceptibility testing revealed that Chryseobacterium isolates were sensitive to enrofloxacin, oxolinic acid, and ciprofloxacin, but exhibited pronounced resistance to most β-lactam and aminoglycoside antibiotics. A total of 19 lytic phages (CV1 – CV19) were successfully isolated. They displayed latent periods between 2.5 and 7.5 h and burst sizes ranging from 20 to 235 PFU per cell. The highest burst size and shortest latent period were recorded for the CV5 phage. Adsorption rate constants showed phage-specific variability, with overall values ranging from 1.05×10⁻⁶ to 2.55×10⁻⁶ mL·min⁻¹. Genome sizes were estimated at 48 – 75 kb. TEM revealed typical tailed morphologies consistent with the order Caudovirales. Host range assays showed strong species specificity, with limited cross-activity against Flavobacterium psychrophilum and Enterococcus faecalis. The findings confirm that these phages possess traits favorable for use as eco-friendly biocontrol agents, offering a promising strategy to mitigate Chryseobacterium-associated infections and reduce antibiotic dependence in trout hatcheries.

ABSTRACT The chemical composition of propolis (a phytochemical-rich, health-promoting bee product) varies highly with region and season, necessitating its thorough characterization. In this study, the chemical profiling of Qatari propolis (QP) was investigated using HPLC-QTOF-MS, along with its antioxidant activity in the ABTS assay. The yield of QP hydroalcoholic extracts (70%), their total flavonoid content (TFC), and total phenolic content (TPC) were in the ranges of 7.83–33.47%, 4.2–21.6%, and 3–14%, respectively. With increasing extract yield, the amount of TFC and TPC also increased. However, the observed promising antioxidant activity of QP samples was not linked to their TPC and TFC, probably because it depends on phenolic and flavonoid composition rather than their quantities. In the QP samples, compounds from different classes, such as flavonoids, fatty acyl glycosides, peptides, monoacyl glycerols, alkaloids, amino glycosides, cinnamic acids and derivatives, coumarins, phenolic glycosides, fatty amides, fatty acids, and derivatives were identified. Among these, flavonoids was the largest class, of which more than half of the compounds were prenylated flavonoids. This highlights the presence of prenylated flavonoids as a unique characteristic of QP. Altogether, QP samples could be a unique natural ingredient for the healthcare and food sectors.

Gentamicin (GET) is a commonly prescribed aminoglycoside antibiotic used to treat severe bacterial infections, but its therapeutic effectiveness is limited by its cardiotoxicity, which is mainly caused by oxidative damage and inflammation. This study investigated the cardioprotective role of vincamine (VIN) against GET-induced cardiac injury. Adult male rats were divided into four groups and treated for 7 days with either CMC (control), VIN, GET, or a combination of GET and VIN. Measurements included oxidative stress markers (TAC and MDA), gene expression of inflammatory cytokines and apoptosis markers (TNF-α, IL-6, Bax, Bcl-2) by qRT-PCR, protein levels of signaling molecules (Nrf2/HO-1, WNT-4, pGSK-3β, β-catenin, pERK, Klotho) by qRT-PCR and ELISA, and NF-κB protein quantification via Western blot. Cardiac tissue was also examined histologically for structural changes. Results demonstrated that VIN significantly reduced GET-induced cardiac damage by modulating crucial signaling pathways and markedly diminished the tissue structural alterations caused by GET. These findings suggest that VIN may serve as a promising cardioprotective agent against GET-induced toxicity through the regulation of pathways including Nrf2/HO-1, pERK/NF-κB, WNT-4/pGSK-3β/β-catenin, and Bax/Bcl-2.

Background/Objectives: Despite their long history of clinical use, aminoglycosides remain important broad-spectrum antibiotics, exhibiting potent activity against Gram-positive, Gram-negative, and mycobacterial pathogens. However, the growing prevalence of antimicrobial resistance, along with the well-documented nephrotoxicity and ototoxicity associated with this class, underscores the urgent need for novel derivatives with enhanced pharmacological and safety profiles. Methods: In this study, we developed a synthetic approach for the synthesis of new apramycin derivatives featuring structural modifications at the 6″-position of 4-amino-4-deoxy-D-glucose residue, specifically through the introduction of aminoalkylamine and guanidinoalkylamine substituents. The synthesized compounds were evaluated for their antimicrobial activity against a broad panel of bacterial strains, including multidrug-resistant clinical isolates. Results: The obtained derivatives of apramycin demonstrated significant antibacterial activity, retaining potency against strains resistant to conventional aminoglycosides. Moreover, the new compounds exhibited the ability to circumvent aminoglycoside resistance mediated by enzymatic modification and showed reduced cytotoxicity in mammalian cell assays. Conclusions: The distinctive pharmacological properties of apramycin and its newly synthesized derivatives, particularly their resilience to common resistance mechanisms and low cytotoxicity, highlight apramycin as a valuable structural scaffold for the development of next-generation aminoglycoside antibiotics with improved efficacy and safety.

Antibiotic resistance is rapidly emerging as one of the most critical health threats, with resistant microorganisms progressively diminishing the effectiveness of established antibiotics. As a result, the development of therapeutic approaches that effectively target resistant pathogens is of utmost importance. In this study, we developed inhibitors for APH(2")-IVa, a bacterial kinase conveying resistance to aminoglycoside antibiotics. Starting from a hit of a fragment-based screening, we explored the inhibitory motif by structure-based design, ultimately leading to a series of triazole analogues. Advanced analogues displayed promising ADME properties, emerging selectivity vs a panel of human kinases, permeability in both Gram-positive and Gram-negative bacteria, and a moderate antibiotic efficacy for clinical strains of P. aeruginosa. Taken together, our results suggest inhibition of bacterial kinases could be a promising option to reinstall the efficacy of aminoglycoside antibiotics.

A coumarin-benzothiazole probe-driven multimodal aptasensing platform for label-free analysis and portable visualization of kanamycin in milks.

Abstract The chemical approach was used for the preparation of silver and gold nanoparticles assisted by ionic surfactant. In this study, trisodium citrate was utilized as an ionic surfactant to explore its ability as a linker or binder between silver/gold nanoparticles (AgNPs/AuNPs) and aminoglycoside antibiotic (amikacin). The resulting surfactant assisted AgNPs and AuNPs were characterized using various analytical techniques such as absorption spectroscopy (UV-Visible), diffraction method (X-ray diffraction) and Transmission electron microscopy (TEM) to examine the interaction process of the drug with nanoparticle surface. Findings revealed that citrate is not an effective mediator for amikacin binding to AgNPs surface in case of silver, as silver loses its surface plasmon resonance (SPR) following the introduction of amikacin results in the production of unstable sulphur compounds. The formation of unstable sulphur compounds is also confirmed from XRD pattern. In contrast, the XRD pattern for AuNPs showed a minor shift in each refection line, in comparison with bare AuNPs, when loaded with amikacin. Moreover, TEM analysis verified that there are no morphological changes in case of AuNPs after the formation of drug nanoconjugates. Therefore, citrate can act as an efficient bridge binding amikacin with the AuNPs surface.