Aminoglycoside antibiotics have played a critical role in the treatment of both Gram-negative and Gram-positive bacterial infections. However, antibiotic resistance has severely compromised the efficacy of aminoglycosides. A leading cause of aminoglycoside resistance is mediated by bacterial enzymes that inactivate these drugs via chemical modification. Aminoglycoside nucleotidyltransferase-6 (ANT(6)) enzymes inactivate streptomycin by transferring an adenyl group from ATP to position 6 on the antibiotic. Despite the clinical significance of this activity, ANT(6) enzymes remain relatively uncharacterized. Here, we report the first high resolution x-ray crystallographic structure of ANT(6)-Ib from Campylobacter fetus subsp. fetus bound with streptomycin. Structural modeling and gel filtration chromatography experiments suggest that the enzyme exists as a dimer in which both subunits contribute to the active site. Moreover, superposition of the ANT(6)-Ib structure with the structurally related enzyme lincosamide nucleotidyltransferase B (LinB) permitted the identification of a putative nucleotide binding site. These data also suggest that residues D44 and D46 coordinate essential divalent metal ions and D102 functions as the catalytic base.

Tuberculosis is a global public health concern. Earlier reports suggested the emergence of high rates of drug resistant tuberculosis in Egypt. This study included 102 isolates of Mycobacterium tuberculosis collected from two reference laboratories in Cairo and Alexandria. All clinical isolates were sub-cultured on Löwenstein-Jensen medium and analyzed using both BD BACTEC MGIT 960 SIRE Kit and standard diffusion disk assays to identify the antibiotic sensitivity profile. Extracted genomic DNA was subjected to whole genome sequencing (WGS) using Illumina platform. Isolates that belong to lineage 4 represented > 80%, while lineage 3 represented only 11% of the isolates. The percentage of drug resistance for the streptomycin, isoniazid, rifampicin and ethambutol were 31.0, 17.2, 19.5 and 20.7, respectively. Nearly 47.1% of the isolates were sensitive to the four anti-tuberculous drugs, while only one isolate was resistant to all four drugs. In addition, several new and known mutations were identified by WGS. High rates of drug resistance and new mutations were identified in our isolates. Tuberculosis control measures should focus on the spread of mono (S, I, R, E)- and double (S, E)-drug resistant strains present at higher rates throughout the whole Nile Delta, Egypt.

UNASSIGNED: Tuberculosis (TB) remains a major health threat worldwide, and the spread of drug-resistant (DR) TB impedes the reduction of the global disease burden. Ebselen (EbSe) targets bacterial thioredoxin reductase (bTrxR) and causes an imbalance in the redox status of bacteria. Previous work has shown that the synergistic action of bTrxR and sensitization to common antibiotics by EbSe is a promising strategy for the treatment of DR pathogens. Thus, we aimed to evaluate whether EbSe could enhance anti-TB drugs against Mycobacterium marinum (M. marinum) which is genetically related to Mycobacterium tuberculosis (Mtb) and resistant to many antituberculosis drugs.
UNASSIGNED: Minimum inhibitory concentrations (MIC) of isoniazid (INH), rifampicin (RFP), and streptomycin (SM) against M. marinum were determined by microdilution. The Bliss Independence Model was used to determine the adjuvant effects of EbSe over the anti-TB drugs. Thioredoxin reductase activity was measured using the DTNB assay, and its effects on bacterial redox homeostasis were verified by the elevation of intracellular ROS levels and intracellular GSH levels. The adjuvant efficacy of EbSe as an anti-TB drug was further evaluated in a mouse model of M. marinum infection. Cytotoxicity was observed in the macrophage cells Raw264.7 and mice model.
UNASSIGNED: The results reveal that EbSe acts as an antibiotic adjuvant over SM on M. marinum. EbSe + SM disrupted the intracellular redox microenvironment of M. marinum by inhibiting bTrxR activity, which could rescue mice from the high bacterial load, and accelerated recovery from tail injury with low mammalian toxicity.
UNASSIGNED: The above studies suggest that EbSe significantly enhanced the anti-Mtb effect of SM, and its synergistic combination showed low mammalian toxicity in vitro and in vivo. Further efforts are required to study the underlying mechanisms of EbSe as an antibiotic adjuvant in combination with anti-TB drug MS.

The chapter presents a technique for inducing spontaneous mutations using antibiotics that target microbial ribosomes and/or RNA polymerase, employed in bacterial breeding. In contrast to UV-based mutagenesis, this method allows control of the mutation sites, specifically targeting the rpsL gene. The outlined methodology introduces spontaneous mutations using streptomycin in Lacticaseibacillus rhamnosus GG ATCC 53103 (LGG), a widely studied lactic acid bacterium. Streptomycin has been shown to induce mutations in the rpsL gene, particularly altering lysine residues at position 56 or 101. It has also been reported to affect bacterial morphology and surface protein composition, thereby enhancing adhesion to human mucin.

BACKGROUND: In clinical practice guidelines, there is no consensus about the medications that should be initially offered to patients with brucellosis. To provide informative evidence, we compared and ranked brucellosis medications based on their efficacy and safety.
METHODS: For this systematic review and network meta-analysis, we searched 4 English databases and 3 Chinese databases, from the date of database inception to December 13, 2023. We included randomized controlled trials (RCTs) involving children and adolescents with brucellosis, comparing different antibiotic regimens. We excluded studies explicitly targeting patients with spondylitis brucellosis, endocarditis brucellosis, and neuro-brucellosis. The primary outcomes were overall failure (efficacy) and side effects (safety). Secondary outcomes were relapse and therapeutic failure. Pairwise meta-analysis was first examined. Data were analyzed using random effects network meta-analysis, with subgroup and sensitivity analyses performed. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was preregistered in PROSPERO (CRD42023491331).
RESULTS: Of the 11,747 records identified through the database search, 43 RCTs were included in the network meta-analysis. Compared with standard therapy (Doxycycline + Rifampicin), Rifampicin + Tetracyclines (RR 4.96; 95% CI 1.47 to 16.70; very low certainty of evidence), Doxycycline + TMP/SMX (RR 0.18; 95% CI 0.06 to 0.52; low certainty of evidence), Doxycycline + Quinolones (RR 0.27; 95% CI 0.11 to 0.71; low certainty of evidence), Streptomycin + Tetracyclines (RR 0.04; 95% CI 0.01 to 0.16; low certainty of evidence), and Single (RR 0.05; 95% CI 0.02 to 0.16; moderate certainty of evidence) were less efficacious. Doxycycline + Gentamicin ranked the best in efficacy (SUCRA values: 0.94), the second is Triple (SUCRA values: 0.87), and the third is Doxycycline + Streptomycin (SUCRA values: 0.78).
CONCLUSIONS: Brucellosis medications differ in efficacy and safety. Doxycycline + Gentamicin, Triple, and Doxycycline + Streptomycin have superior efficacy and safety. Treatment of brucellosis should strike a balance between efficacy, safety, and cost.

Brucellosis is a difficult to treat infection that requires antibiotic combinations administered over several weeks for clearance of infection and relapse prevention. This systematic review summarizes current evidence for antibiotic treatment of human brucellosis. PubMed, EMBASE, Scopus, CINAHL, Web of Science, and China Academic Journal databases were searched for prospective studies that had compared different antibiotic regimens for treating human brucellosis in the last 25 years. Thirty-four studies recruiting 4182 participants were eligible. Standard dual therapy with doxycycline + rifampicin had a higher risk of treatment failure compared to triple therapy which added streptomycin (RR: 1.98, 95% CI 1.17-3.35, p = 0.01) or levofloxacin (RR: 2.98, 95% CI 1.67-5.32, p = 0.0002), but a similar or lower risk compared to alternative dual antibiotic combinations (p > 0.05). The same combination had a higher risk of relapses compared to triple therapy which added streptomycin (RR: 22.12, 95% CI 3.48-140.52, p = 0.001), or levofloxacin (RR: 4.61, 95% CI 2.20-9.66, p < 0.0001), but a similar or lower risk compared to other dual antibiotic combinations (p > 0.05). Triple antibiotic therapy is more effective than standard dual therapy with rifampicin and doxycycline. However, the latter is also efficacious and suitable for uncomplicated disease.

This article presents a new method for preparing multifunctional composite biomaterials with applications in advanced biomedical fields. The biomaterials consist of dicalcium phosphate (DCPD) and bioactive silicate glasses (SiO2/Na2O and SiO2/K2O), containing the antibiotic streptomycin sulfate. Materials were deeply characterized by X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy, and zeta potential analysis, UV-visible spectrophotometry, and ion-exchange measurement were applied in a simulating body fluid (SBF) solution. The main results include an in situ chemical transformation of dicalcium phosphate into an apatitic phase under the influence of silicate solutions and the incorporation of the antibiotic. The zeta potential showed a decrease in surface charge from ζ = -24.6 mV to ζ = -16.5 mV. In addition, a controlled and prolonged release of antibiotics was observed over a period of 37 days, with a released concentration of up to 755 ppm. Toxicity tests in mice demonstrated good tolerance of the biomaterials, with no significant adverse effects. Moreover, these biomaterials have shown potent antibacterial activity against various bacterial strains, including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, suggesting their potential use in tissue engineering, drug delivery, and orthopedic and dental implants. By integrating the antibiotic into the biomaterial composites, we achieved controlled release and prolonged antibacterial efficacy. This research contributes to advancing biomaterials by exploring innovative synthetic routes and showcasing their promise in regenerative medicine and controlled drug delivery.

BACKGROUND: In our study, we aimed to evaluate the epidemiological features of brucellosis and the efficacy of different treatment options in patients with various organ involvements.
METHODS: Patients diagnosed with brucellosis and treated in two different centers between 2009 and 2019 were retrospectively screened and evaluated regarding epidemiological and clinical features, laboratory findings, and treatment responses.
RESULTS: The study included 297 complete-data patients (76% of rural patients were farmers). Farming (76%) and raw dairy (69%) were the main transmission methods. Most patients (98.6%) had positive tube agglutination tests. Ninety-two patients\' blood and bodily fluid cultures grew Brucella spp. The incidence of leukopenia was 18.8%, thrombocytopenia 10.7%, anemia 34.3%, and pancytopenia 4.3%. Doxycycline and rifampicin were the major treatments, with streptomycin utilized in osteoarticular patients. Pregnant women with neurobrucellosis took ceftriaxone and trimethoprim-sulfamethoxazole. After one year, 7.1% of patients relapsed. Doxycycline + streptomycin and doxycycline + rifampicin had similar relapse rates (p = 0.799). The double- and triple-antibiotic groups had identical recurrence rates (p = 0.252).
CONCLUSIONS: In uncomplicated brucellosis cases doxycycline + streptomycin and doxycycline + rifampicin treatments were equally effective. Again, there is no statistical difference in relapse development rates between double and triple combination treatments in uncomplicated brucellosis cases. Relapsed patients generally miss follow-ups, interrupt therapy, have osteoarticular involvement, and get short-term treatment. Patients with focused participation should be thoroughly checked at diagnosis and medicine, and treatment should be lengthy to prevent relapses.

BACKGROUND: Isoniazid (INH) and Rifampicin (RIF) are two crucial drugs used in antitubercular therapy. INH is known for its potent bactericidal effects and has a relatively higher prevalence of resistance compared to RIF. However, RIF resistance has been the subject of more extensive research. On the other hand, Ethambutol (EMB) and Streptomycin (STR) resistance have not been thoroughly studied, particularly in the context of children and adolescents. To address this knowledge gap, a study was designed to investigate the resistance patterns of INH, EMB, and STR in RIF-sensitive pulmonary tuberculosis (PTB) cases among children and adolescents.
METHODS: Seventy-five newly diagnosed RIF sensitive PTB cases up to 18 years of age were enrolled. Retreatment cases were excluded. Sputum/gastric aspirate sample of these patients were sent for culture in Mycobacterium Growth Indicator Tube (MGIT) followed by drug susceptibility testing and Line Probe Assay.
RESULTS: INH, EMB and STR resistance among RIF sensitive PTB cases was found to be 5.7%, 0% and 0.7% respectively. RIF resistance detected by CBNAAT was found to be 8.4%.
CONCLUSIONS: Detection of INH resistance is as important as detecting RIF resistance as prevalence of INH resistance in RIF sensitive PTB among children and adolescents up to 18 years is around 6%.

Just as the human gut microbiome is colonized by a variety of microbes, so too is the rhizosphere of plants. An imbalance in this microbial community, known as dysbiosis, can have a negative impact on plant health. This study sought to explore the effect of rhizosphere dysbiosis on the health of tomato plants (Solanum lycopersicum L.), using them and the foliar bacterial spot pathogen Xanthomonas perforans as model organisms. The rhizospheres of 3-week-old tomato plants were treated with either streptomycin or water as a control, and then spray-inoculated with X. perforans after 24 h. Half of the plants that were treated with both streptomycin and X. perforans received soil microbiome transplants from uninfected plant donors 48 h after the streptomycin was applied. The plants treated with streptomycin showed a 26% increase in disease severity compared to those that did not receive the antibiotic. However, the plants that received the soil microbiome transplant exhibited an intermediate level of disease severity. The antibiotic-treated plants demonstrated a reduced abundance of rhizobacterial taxa such as Cyanobacteria from the genus Cylindrospermum. They also showed a down-regulation of genes related to plant primary and secondary metabolism, and an up-regulation of plant defence genes associated with induced systemic resistance. This study highlights the vital role that beneficial rhizosphere microbes play in disease resistance, even against foliar pathogens.