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Journal of Bacteriology Sep 2023Streptomycin (Sm) is a commonly used antibiotic for its efficacy against diverse bacteria. The plant pathogen is a model for studying pathogenesis and interkingdom gene...
Streptomycin (Sm) is a commonly used antibiotic for its efficacy against diverse bacteria. The plant pathogen is a model for studying pathogenesis and interkingdom gene transfer. Streptomycin-resistant variants of are commonly employed in genetic analyses, yet mechanisms of resistance and susceptibility to streptomycin in this organism have not previously been investigated. We observe that resistance to a high concentration of streptomycin arises at high frequency in , and we attribute this trait to the presence of a chromosomal gene () encoding a putative aminoglycoside phosphotransferase. We show how , along with (encoding ribosomal protein S12) and (encoding a 16S rRNA methyltransferase), modulates streptomycin sensitivity in . IMPORTANCE The plant pathogen is a widely used model bacterium for studying biofilms, bacterial motility, pathogenesis, and gene transfer from bacteria to plants. Streptomycin (Sm) is an aminoglycoside antibiotic known for its broad efficacy against gram-negative bacteria. exhibits endogenous resistance to somewhat high levels of streptomycin, but the mechanism underlying this resistance has not been elucidated. Here, we demonstrate that this resistance is caused by a chromosomally encoded streptomycin-inactivating enzyme, StrB, that has not been previously characterized in . Furthermore, we show how the genes , , and jointly modulate streptomycin susceptibility in .
Topics: Streptomycin; RNA, Ribosomal, 16S; Agrobacterium; Anti-Bacterial Agents
PubMed: 37695858
DOI: 10.1128/jb.00165-23 -
Proceedings of the Royal Society of... Nov 1952
Topics: Dihydrostreptomycin Sulfate; Streptomycin
PubMed: 13003993
DOI: No ID Found -
British Medical Journal May 1952
Topics: Dihydrostreptomycin Sulfate; Humans; Streptomycin
PubMed: 14925373
DOI: No ID Found -
Biomedicine & Pharmacotherapy =... Feb 2023Brucellosis is considered one of the most important infectious diseases affecting any tissue and organ in the human body. Due to the intracellular pathogenesis of...
Use of the quantum dot-labeled solid lipid nanoparticles for delivery of streptomycin and hydroxychloroquine: A new therapeutic approach for treatment of intracellular Brucella abortus infection.
Brucellosis is considered one of the most important infectious diseases affecting any tissue and organ in the human body. Due to the intracellular pathogenesis of Brucella species, the use of conventional antibiotics for managing chronic brucellosis has several limitations. Therefore, the study focused on the use of solid lipid nanoparticles (SLN) to deliver streptomycin (STR) for intracellular infection, with or without the combination of hydroxychloroquine (HCQ) to evaluate if there might be a boost in the antibiotic effect when using the STR or STR-NPs alone. We used the double emulsion technique to synthesize Nano drug carriers; afterward, the physicochemical characteristics of synthesized Nano drug carriers were determined. The in vitro antibacterial activity of free drugs and Nano drug carriers were evaluated using well diffusion, broth microdilution assays (BMD), and murine macrophage-like cells cell line J774A.1. Additionally, acute and chronic phases of brucellosis were inducted into Wistar rats, and healing capacity of Nano drug carriers on liver and spleen tissues was compared with free drugs. The zeta potential of nanoparticles, means of size, Polydispersity Index (PDI), drugs loading, and encapsulation efficiency were 15.2 mV, 312.5 ± 26 nm, 0.433 ± 0.09, 16.6% and 89.5%, respectively. Well diffusion and BMD methods did not show a significantly differ between free drugs and nano drug carriers. However, the Nano drug carriers remarkably decreased the number of bacteria in the cell line compared to the free drugs. STR/HCQ-SLN enhanced the healing processes of the liver and spleen after brucellosis induction. STR/HCQ-SLN showed better inhibitory effects against the chronic phase of B. abortus infection in comparison to the STR-SLN, but this difference was not statistically significant. Using nanoplatforms to enhance conventional anti-brucellosis agents is promising, green and safe. Due to the continuous release of drugs, drugs increase their accumulation at the site of infection, causing a more significant effect on the chronic and acute phases of brucellosis.
Topics: Rats; Mice; Humans; Animals; Brucella abortus; Streptomycin; Hydroxychloroquine; Quantum Dots; Rats, Wistar; Brucellosis; Nanoparticles; Anti-Bacterial Agents; Drug Carriers
PubMed: 36527846
DOI: 10.1016/j.biopha.2022.114116 -
International Journal of Molecular... Jan 2022The preparation, characterization, and controlled release of hydroxyapatite (HAp) nanoparticles loaded with streptomycin (STR) was studied. These nanoparticles are...
The preparation, characterization, and controlled release of hydroxyapatite (HAp) nanoparticles loaded with streptomycin (STR) was studied. These nanoparticles are highly appropriate for the treatment of bacterial infections and are also promising for the treatment of cancer cells. The analyses involved scanning electron microscopy, dynamic light scattering (DLS) and Z-potential measurements, as well as infrared spectroscopy and X-ray diffraction. Both amorphous (ACP) and crystalline (cHAp) hydroxyapatite nanoparticles were considered since they differ in their release behavior (faster and slower for amorphous and crystalline particles, respectively). The encapsulated nanoparticles were finally incorporated into biodegradable and biocompatible polylactide (PLA) scaffolds. The STR load was carried out following different pathways during the synthesis/precipitation of the nanoparticles (i.e., nucleation steps) and also by simple adsorption once the nanoparticles were formed. The loaded nanoparticles were biocompatible according to the study of the cytotoxicity of extracts using different cell lines. FTIR microspectroscopy was also employed to evaluate the cytotoxic effect on cancer cell lines of nanoparticles internalized by endocytosis. The results were promising when amorphous nanoparticles were employed. The nanoparticles loaded with STR increased their size and changed their superficial negative charge to positive. The nanoparticles' crystallinity decreased, with the consequence that their crystal sizes reduced, when STR was incorporated into their structure. STR maintained its antibacterial activity, although it was reduced during the adsorption into the nanoparticles formed. The STR release was faster from the amorphous ACP nanoparticles and slower from the crystalline cHAp nanoparticles. However, in both cases, the STR release was slower when incorporated in calcium and phosphate during the synthesis. The biocompatibility of these nanoparticles was assayed by two approximations. When extracts from the nanoparticles were evaluated in cultures of cell lines, no cytotoxic damage was observed at concentrations of less than 10 mg/mL. This demonstrated their biocompatibility. Another experiment using FTIR microspectroscopy evaluated the cytotoxic effect of nanoparticles internalized by endocytosis in cancer cells. The results demonstrated slight damage to the biomacromolecules when the cells were treated with ACP nanoparticles. Both ACP and cHAp nanoparticles were efficiently encapsulated in PLA electrospun matrices, providing functionality and bioactive properties.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; COS Cells; Cell Line, Tumor; Chlorocebus aethiops; Drug Delivery Systems; Durapatite; Humans; Nanoparticles; Polyesters; Streptomycin; Tissue Scaffolds; Vero Cells
PubMed: 35163204
DOI: 10.3390/ijms23031282 -
Journal of Chromatography. A Feb 2021In this fundamental study, streptomycin was extracted successfully from urine and plasma using electromembrane extraction (EME). Streptomycin is an aminoglycoside with...
In this fundamental study, streptomycin was extracted successfully from urine and plasma using electromembrane extraction (EME). Streptomycin is an aminoglycoside with log P -7.6 and was selected as an extremely polar model analyte. EME is a microextraction technique, where charged analytes are extracted under the influence of an electrical field, from sample, through a supported liquid membrane (SLM), and into an acceptor solution. The SLM comprised 2-nitrophenyl pentyl ether (NPPE) mixed with bis(2-ethylhexyl) phosphate (DEHP). DEHP served as ionic carrier and facilitated transfer of streptomycin across the SLM. For EME from urine and protein precipitated plasma, the optimal DEHP content in the SLM was 45-50% w/w. From untreated plasma, the content of DEHP was increased to 75% w/w in order to suppress interference from plasma proteins. Most endogenous substances with UV absorbance were not extracted into the acceptor. Proteins and phospholipids were also discriminated, with <0.6% of proteins and <0.02% of phospholipids found in the acceptor after EME. Thus, despite the fact that the SLM was permeable to more polar molecules, the EME still provided very efficient sample cleanup. Extraction process efficiencies of 98% and 61% were achieved from urine and plasma, respectively, with linear calibration (R > 0.9929), absence of significant matrix effects (94-112%), accuracy of 94-125%, and RSD ≤ 15% except at LLOQ. The average current during extractions was 67 µA or less. The findings of this paper demonstrated that EME is feasible for extraction of basic analytes of extreme polarity.
Topics: Chromatography, Liquid; Electricity; Hydrogen-Ion Concentration; Membranes, Artificial; Reproducibility of Results; Solvents; Streptomycin; Tandem Mass Spectrometry
PubMed: 33535115
DOI: 10.1016/j.chroma.2021.461915 -
ELife Dec 2022The mitoribosome regulates cellular energy production, and its dysfunction is associated with aging. Inhibition of the mitoribosome can be caused by off-target binding...
The mitoribosome regulates cellular energy production, and its dysfunction is associated with aging. Inhibition of the mitoribosome can be caused by off-target binding of antimicrobial drugs and was shown to be coupled with a bilateral decreased visual acuity. Previously, we reported mitochondria-specific protein aspects of the mitoribosome, and in this article we present a 2.4-Å resolution structure of the small subunit in a complex with the anti-tuberculosis drug streptomycin that reveals roles of non-protein components. We found iron-sulfur clusters that are coordinated by different mitoribosomal proteins, nicotinamide adenine dinucleotide (NAD) associated with rRNA insertion, and posttranslational modifications. This is the first evidence of inter-protein coordination of iron-sulfur, and the finding of iron-sulfur clusters and NAD as fundamental building blocks of the mitoribosome directly links to mitochondrial disease and aging. We also report details of streptomycin interactions, suggesting that the mitoribosome-bound streptomycin is likely to be in hydrated gem-diol form and can be subjected to other modifications by the cellular milieu. The presented approach of adding antibiotics to cultured cells can be used to define their native structures in a bound form under more physiological conditions, and since streptomycin is a widely used drug for treatment, the newly resolved features can serve as determinants for targeting.
Topics: Streptomycin; NAD; Sulfur
PubMed: 36480258
DOI: 10.7554/eLife.77460 -
Scientific Reports Nov 2023Antibiotics are chemical compounds that are used to treat and prevent disease in humans and animals. They have been used in animal feed for over 60 years and are widely...
Antibiotics are chemical compounds that are used to treat and prevent disease in humans and animals. They have been used in animal feed for over 60 years and are widely used in industrial farming. Antibiotics can have negative environmental impacts, including the potential to contribute to the development of antibiotic-resistant organisms. They can enter the environment through various pathways, including the manufacturing process, the direct application of antibiotic-laden manure to fields, and through grazing animals. Antibiotics that are given to animals can be excreted from where they can enter soil and groundwater which enable their entry in plants. Streptomycin is an antibiotic that is used against a range of gram-positive and gram-negative bacteria, but its use has led to the development of antibiotic resistance in some pathogens. It has also been shown to have negative impacts on a range of plant species, including tobacco, tomato, and wheat. Although, the major effect of streptomycin on plant physiology have been studied, the molecular mechanisms at play are barely understood in plant body. In current study, we examined the impact of streptomycin on germination of Brassica napus and then using docking, MM-GBBSA and MD simulations identified key proteins that interact with streptomycin by performing rigorous computational screening of 106 different proteins. Our finding suggest that streptomycin might be interacting with acyl-CoA oxidases, protochlorophyllide reductase B and leucoanthocyanidin dioxygenase based on simulation and docking analysis.
Topics: Humans; Animals; Streptomycin; Brassica napus; Anti-Bacterial Agents; Molecular Dynamics Simulation; Gram-Negative Bacteria; Gram-Positive Bacteria
PubMed: 37925515
DOI: 10.1038/s41598-023-46100-4 -
Marine Drugs Jan 2019Microbial biofilms are considerably more resistant to antibiotics than planktonic cells. It has been reported that chitosan coupling with the aminoglycoside antibiotic...
Microbial biofilms are considerably more resistant to antibiotics than planktonic cells. It has been reported that chitosan coupling with the aminoglycoside antibiotic streptomycin dramatically disrupted biofilms of several Gram-positive bacteria. This finding suggested the application of the covalent conjugate of antimicrobial natural polysaccharides and antibiotics on anti-infection therapy. However, the underlying molecular mechanism of the chitosan-streptomycin conjugate (CS-Strep) remains unclear and the poor water-solubility of the conjugate might restrict its applications for anti-infection therapy. In this study, we conjugated streptomycin with water-soluble chitosan oligosaccharides (COS). Unlike CS-Strep, the COS-streptomycin conjugate (COS-Strep) barely affected biofilms of tested Gram-positive bacteria. However, COS-Strep efficiently eradicated established biofilms of the Gram-negative pathogen . This activity of COS-Strep was influenced by the degree of polymerization of chitosan oligosaccharide. The increased susceptibility of biofilms to antibiotics after conjugating might be related to the following: Suppression of the activation of MexX-MexY drug efflux pump system induced by streptomycin treatment; and down-regulation of the biosynthesis of biofilm exopolysaccharides. Thus, this work indicated that covalently linking antibiotics to chitosan oligosaccharides was a possible approach for the development of antimicrobial drugs against biofilm-related infections.
Topics: Anti-Bacterial Agents; Biofilms; Carbohydrate Conformation; Chitosan; Human Umbilical Vein Endothelial Cells; Humans; Oligosaccharides; Pseudomonas aeruginosa; Streptomycin
PubMed: 30634609
DOI: 10.3390/md17010043 -
Infection, Genetics and Evolution :... Jan 2024Streptomycin resistance in V. parahaemolyticus has been widespread in both clinical and environmental isolates. Therefore, it is of great significance to characterize...
Streptomycin resistance in V. parahaemolyticus has been widespread in both clinical and environmental isolates. Therefore, it is of great significance to characterize the mechanism of streptomycin resistance in V. parahaemolyticus. O10:K4 has emerged and becoming the new dominant serotype since 2020. In this study, we isolated a total of 36 strains of V. parahaemolyticus O10:K4 from 2020 to 2022 and found that more than half of them were resistant to streptomycin. We obtained streptomycin resistant and sensitive strains by detecting the resistance profiles. Whole-genome sequencing showed that VP_RS10735 and VP_RS05605 were the predominant mutations in streptomycin resistant O10:K4 clinical isolates. In addition, this study provided global insight into the characteristics of the transcriptome signature of streptomycin resistance, revealing that efflux transporters play a key role in streptomycin resistance. Finally, we found that streptomycin resistant strain was more virulent than sensitive strain. The results of this study should advance our understanding of the mechanisms of aminoglycoside resistance.
Topics: Humans; Streptomycin; Vibrio parahaemolyticus; Transcriptome; Anti-Bacterial Agents; Whole Genome Sequencing; Vibrio Infections
PubMed: 38114043
DOI: 10.1016/j.meegid.2023.105540