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Antibiotic abuse is becoming increasingly serious and the potential for harm to human health and the environment has aroused widespread social concern. Aminoglycoside antibiotics (AGs) are broad-spectrum antibiotics that have been widely used in clinical and animal medicine. Consequently, their residues are commonly found in animal-derived food items and the environment. A simple, rapid, and sensitive detection method for on-site screening and detection of AGs is urgently required. In recent years, with the development of molecular detection technology, nucleic acid aptamers have been successfully used as recognition molecules for the identification and detection of AGs in food and the environment. These aptamers have high affinities, selectivities, and specificities, are inexpensive, and can be produced with small batch-to-batch differences. This paper reviews the applications of aptamers for AG detection in colorimetric, fluorescent, chemiluminescent, surface plasmon resonance, and electrochemical sensors for the analysis in food and environmental samples. This study provides useful references for future research.

Investigation of aminoglycoside acetyltransferases in actinobacteria of the genus Streptomyces is an integral part of the study of soil bacteria as the main reservoir and possible source of drug resistance genes. Previously, we have identified and biochemically characterized three aminoglycoside phosphotransferases, which cause resistance to kanamycin, neomycin, paromomycin, streptomycin, and hygromycin B in the strain Streptomyces rimosus ATCC 10970 (producing oxytetracycline), which is resistant to most natural aminoglycoside antibiotics. In the presented work, it was shown that the resistance of this strain to other AGs is associated with the presence of the enzyme aminoglycoside acetyltransferase, belonging to the AAC(2′) subfamily. Induction of the expression of the gene, designated by us as aac(2′)-If, in Escherichia coli cells determines resistance to a wide range of natural aminoglycoside antibiotics (neomycin, gentamicin, tobramycin, sisomycin, and paromomycin) and increases minimum inhibitory concentrations of these antibiotics.

Background Response surface methodology (RSM) employing Box-Behnken design was used to optimize the environmental factors for the production of paromomycin, a 2 deoxystreptamine aminocyclitol aminoglycoside antibiotic, (2DOS-ACAGA) from Streptomyces (S.) rimosus NRRL 2455. Emergence of bacterial resistance caught our attention to consider the combination of antimicrobial agents. The effect of paromomycin combination with other antimicrobial agents was tested on some multiple drug resistant isolates. To the best of our knowledge, this is the first report on optimization of paromomycin production from S. rimosus NRRL 2455. A Quadratic model and response surface method were used by choosing three model factors; pH, incubation time and inoculum size. A total of 17 experiments were done and the response of each experiment was recorded. Concerning the effect of combining paromomycin with different antimicrobial agents, it was tested using the checkerboard assay against six multidrug resistant (MDR) pathogens including; Pseudomonas (P.) aeruginosa (2 isolates), Klebsiella (K.) pneumoniae , Escherichia (E.) coli , methicillin sensitive Staphylococcus aureus (MSSA) and methicillin resistant Staphylococcus aureus (MRSA). Paromomycin was tested in combination with ceftriaxone, ciprofloxacin, ampicillin/sulbactam, azithromycin, clindamycin and doxycycline. Results The optimum conditions for paromomycin production were a pH of 6, an incubation time of 8.5 days and an inoculum size of 5.5% v /v using the optimized media (soybean meal 30 g/L, NH 4 CL 4 g/L, CaCO 3 5 g/L and glycerol 40 ml/L), 28 °C incubation temperature, and 200 rpm agitation rate that resulted in 14 fold increase in paromomycin production as compared to preliminary fermentation level using the basal medium. The tested antibiotic combinations showed either synergistic effect on paromomycin activity on most of the tested MDR pathogens (45.83%), additive effect in 41.67% or indifferent effect in 12.5%. Conclusion RSM using multifactorial design was a helpful and a reliable method for paromomycin production. Paromomycin combination with ceftriaxone, ciprofloxacin, ampicillin/sulbactam, azithromycin, clindamycin or doxycycline showed mostly synergistic effect on certain selected clinically important MDR pathogens.

Etimicin is a fourth-generation aminoglycoside antibiotic. It has potent activity and low toxicity when employed for the treatment of Gram-negative and Gram-positive bacterial infections. The pharmacokinetics of etimicin in humans have not been elucidated completely. Two liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical methods, without the use of any ion-pairing reagents, were developed and validated for the quantification of etimicin in human samples of serum and urine. Using a deuterated reagent as the internal standard, analytes in serum and urine samples were extracted by protein precipitation and dilution before LC-MS/MS analysis, respectively. For the two methods, chromatographic separations were undertaken under isocratic elution of water–ammonia solution–acetic acid (96:3.6:0.2, v/v/v ) and methanol at 50%:50% and a flow rate of 0.35 ml/min within 5 min. A Waters XTerra MS C18 column (2.1 × 150 mm, 3.5 μm) and a column temperature of 40°C were chosen. A Sciex Qtrap 5500 mass spectrometer equipped with an electrospray ion source was used in both methods under multiple-reaction monitoring in positive-ion mode. The two methods showed good linearity, accuracy, and precision with high recovery and a minimal matrix effect in the range of 50.0–20000 ng/ml for serum samples and 50.0–10000 ng/ml for urine samples, respectively. Carry-over effects were not observed. Etimicin remained stable in human samples of serum or urine under the storage, preparation, and analytical conditions of the two methods. These two simple and reliable methods were applied successfully to a dose-escalation, phase I clinical trial of etimicin in Chinese healthy volunteers after intravenous administration of single and multiple doses. Based on these two methods we ascertained, for the first time, the comprehensive pharmacokinetics of etimicin in humans, which will be used for the exploration of the breakpoint research further.

Hearing or balance loss are disabling conditions that have a serious impact in those suffering them, especially when they appear in children. Their ultimate cause is frequently the loss of function of mechanosensory hair cells in the inner ear. Hair cells can be damaged by environmental insults, like noise or chemical agents, known as ototoxins. Two of the most common ototoxins are life-saving medications: cisplatin against solid tumors, and aminoglycoside antibiotics to treat infections. However, due to their localization inside the temporal bone, hair cells are difficult to study in mammals. As an alternative animal model, zebrafish larvae have hair cells similar to those in mammals, some of which are located in a fish specific organ on the surface of the skin, the lateral line. This makes them easy to observe in vivo and readily accessible for ototoxins or otoprotective substances. These features have made possible advances in the study of the mechanisms mediating ototoxicity or identifying new potential ototoxins. Most importantly, the small size of the zebrafish larvae has allowed screening thousands of molecules searching for otoprotective agents in a scale that would be highly impractical in rodent models. The positive hits found can then start the long road to reach clinical settings to prevent hearing or balance loss.

With the increasingly serious problem of aminoglycoside antibiotic residues, it is imperative to develop rapid, sensitive and efficient detection methods. This article reviews the detection methods of aminoglycoside antibiotics in animal-derived foods, including enzyme-linked immunosorbent assay, fluorescent immunoassay, chemical immunoassay, affinity sensing assay, lateral flow immunochromatography and molecular imprinted immunoassay. After evaluating the performance of these methods, the advantages and disadvantages were analyzed and compared. Furthermore, development prospects and research trends were proposed and summarized. This review can serve as a basis for further research and provide helpful references and new insights for the analysis of aminoglycoside residues. Accordingly, the in-depth investigation and analysis will certainly make great contributions to food safety, public hygiene and human health.

The bacterial persisters have emerged as a huge threat to human health. Here, we investigated the role of L-tryptophan in bacterial persister killing by aminoglycoside antibiotics (AGs). The relevance to the antibiotic susceptibility of including transcriptional sequencing, gene expression, intracellular ATP, Nicotinamide adenine dinucleotide (NAD/NADH), reactive oxygen species and membrane depolarization were determined. We found that exogenous L-tryptophan efficiently inhibited AGs-enabled persisters. The flagellar genes were almost significantly downregulated. Besides, the AGs uptake was obviously increased as the result of elevation in proton motive force (PMF) in response to L-tryptophan-mediated NADH production. Taken together, these data supported a novel role of L-tryptophan in eradicating AGs persisters against .

Purpose: Amikacin, a water-soluble aminoglycoside antibiotic used to treat gram-negative bacillary infections, is a Biopharmaceutics Classification System class III drug having poor permeability and short half-life. It is given parenterally, which limits its use in patients warranting \"at-home care.\" An oral drug delivery of amikacin is, therefore, imminent. Aim: This work focused on establishing poly d, l-lactide-co-glycolide (PLGA)-based nanoparticles of amikacin with consolidated pharmaceutical attributes capable of circumventing gastrointestinal tract membrane barriers and promoting oral administration of the drug. The partied attributes are suggestive of enhanced uptake of the drug via Peyer's patches overlaying small intestine and support successful oral delivery. Materials and Methods: To have a robust delivery system, a statistical Box-Behnken experimental design was used and formulation parameters such as homogenization time, probe sonication time, and drug/polymer ratio of amikacin-loaded PLGA nanoparticles (A-NPs) for obtaining monodispersed nanoparticles of adequate size and high drug loading were optimized. Results: The model suggested to use the optimum homogenization time, probe sonication time, and drug/polymer ratio as 30s, 120s, and 1:10, respectively. Under these formulation conditions, the particle size was found to be 260.3nm and the drug loading was 3.645%. Conclusion: Biodegradable PLGA nanoparticulate systems with high payload, optimum size, and low polydispersity index will ensure successful uptake and ultimately leading to better bioavailability. Hence, under the aforementioned optimized conditions, the A-NPs prepared had particle size of 260.3nm, which is appreciable for its permeability across small intestine, and drug loading of 3.645%.

A metagenomic approach and network analysis was used to investigate the wide-spectrum profiles of antibiotic resistance genes (ARGs) and their co-occurrence patterns in 50 samples from 10 typical environments. In total, 260 ARG subtypes belonging to 18 ARG types were detected with an abundance range of 5.4 × 10 −6 –2.2 × 10 −1 copy of ARG per copy of 16S-rRNA gene. The trend of the total ARG abundances in environments matched well with the levels of anthropogenic impacts on these environments. From the less impacted environments to the seriously impacted environments, the total ARG abundances increased up to three orders of magnitude, that is, from 3.2 × 10 −3 to 3.1 × 10 0 copy of ARG per copy of 16S-rRNA gene. The abundant ARGs were associated with aminoglycoside, bacitracin, β-lactam, chloramphenicol, macrolide-lincosamide-streptogramin, quinolone, sulphonamide and tetracycline, in agreement with the antibiotics extensively used in human medicine or veterinary medicine/promoters. The widespread occurrences and abundance variation trend of vancomycin resistance genes in different environments might imply the spread of vancomycin resistance genes because of the selective pressure resulting from vancomycin use. The simultaneous enrichment of 12 ARG types in adult chicken faeces suggests the coselection of multiple ARGs in this production system. Non-metric multidimensional scaling analysis revealed that samples belonging to the same environment generally possessed similar ARG compositions. Based on the co-occurrence pattern revealed by network analysis, tet M and aminoglycoside resistance protein, the hubs of the ARG network, are proposed to be indicators to quantitatively estimate the abundance of 23 other co-occurring ARG subtypes by power functions.

Aminoglycosides are chemically diverse, broad-spectrum antibiotics that target functional centers within the bacterial ribosome to impact all four principle stages (initiation, elongation, termination, and recycling) of the translation mechanism. The propensity of aminoglycosides to induce miscoding errors that suppress the termination of protein synthesis supports their potential as therapeutic interventions in human diseases associated with premature termination codons (PTCs). However, the sites of interaction of aminoglycosides with the eukaryotic ribosome and their modes of action in eukaryotic translation remain largely unexplored. Here, we use the combination of X-ray crystallography and single-molecule FRET analysis to reveal the interactions of distinct classes of aminoglycosides with the 80S eukaryotic ribosome. Crystal structures of the 80S ribosome in complex with paromomycin, geneticin (G418), gentamicin, and TC007, solved at 3.3- to 3.7-Å resolution, reveal multiple aminoglycoside-binding sites within the large and small subunits, wherein the 6′-hydroxyl substituent in ring I serves as a key determinant of binding to the canonical eukaryotic ribosomal decoding center. Multivalent binding interactions with the human ribosome are also evidenced through their capacity to affect large-scale conformational dynamics within the pretranslocation complex that contribute to multiple aspects of the translation mechanism. The distinct impacts of the aminoglycosides examined suggest that their chemical composition and distinct modes of interaction with the ribosome influence PTC read-through efficiency. These findings provide structural and functional insights into aminoglycoside-induced impacts on the eukaryotic ribosome and implicate pleiotropic mechanisms of action beyond decoding.