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Mechanism of Drug Resistance in Staphylococcus aureus and Future Drug Discovery
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Felipe Wakasuqui, Ana Leticia Gori Lusa, Sven Falke, Christian Betzel, Carsten Wrenger
Other antibiotic class, glycopeptides, are glycosylated cyclic or polycyclic non-ribosomal peptides that inhibit the cell wall synthesis by binding to the peptidoglycan, and preventing the addition of new subunits (Courvalin, 2006). The most important member of this class, vancomycin, is the first choice treatment for MRSA infection. Several strains have acquired different patterns of resistance by utilizing diverse mechanisms. Intermediate resistance in VISA (vancomycin-intermediate S. aureus) might be acquired by combination of mutations in several genes. These mutations seem to favor the production of cell wall and decrease autolysis, conferring them moderate resistance (Hiramatsu et al., 2014a). Strains resistant VRSA (vancomycin-resistant S. aureus) acquired the vanA-transposon from vancomycin-resistant Enterococcus (VRE). The vanA gene complex carries four genes that replace the D-Alanyl-D-Alanine residues of proteoglycan by D-Alanyl-D-lactate, inhibiting the action of vancomycin (Courvalin, 2006). Other glycopeptides as oritavancin and telavancin exhibit a dual mechanism, causing membrane damage, and being useful against resistant strains (Zeng et al., 2016).
Pinus wallichiana-synthesized silver nanoparticles as biomedical agents: in-vitro and in-vivo approach
Published in Green Chemistry Letters and Reviews, 2020
Nazish Khan, Ibrar Khan, Akhtar Nadhman, Sadiq Azam, Inam Ullah, Farhan Ahmad, Hamid Ali Khan
The antibacterial activity of synthesized AgNPs was determined against vancomycin-resistant Staphylococcus aureus (VRSA), Pseudomonas aeruginosa, Morganella morganii, Escherichia coli, S. aureus, Proteus vulgaris, and Acinetobacter baumannii. Nutrient agar and broth media were prepared, autoclaved, and incubated for 24 h at 37°C for sterility check. Uniform bacterial lawns were prepared on sterile nutrient agar plates and using 6 mm borers, wells were made. The AgNPs (100 μl) were transferred to respective wells from the stock solution of AgNPs (3 mg/ml of Dimethyl Sulfoxide (<1%)) and incubated at 37°C for 24 h. The Amoxicillin was used as a positive control and DMSO (<1%) as a negative control throughout the experiment. After incubation, zone of inhibition (mm) was measured in comparison with the positive control (15). Minimum bactericidal concentration (MBC) and minimum inhibitory concentration (MIC) were determined as per the reported procedure (16).
Daphne mucronata-mediated phytosynthesis of silver nanoparticles and their novel biological applications, compatibility and toxicity studies
Published in Green Chemistry Letters and Reviews, 2018
Asma Shah, Ghosia Lutfullah, Kafeel Ahmad, Ali Talha Khalil, Malik Maaza
Agar well diffusion method was used for antibacterial activity (34,35). The strains used for antimicrobial studies included Morganella morganii, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Acinetobacter baumannii, vancomycin-resistant Staphylococcus aureus (VRSA) and Proteus vulgaris. A 20 mg/ml stock solution of aqueous extracts and synthesized AgNPs was prepared in dimethylsulfoxide (DMSO). Turbidity of bacterial inoculum was adjusted according to 0.5% McFarland standard. Culture was inoculated on nutrient agar medium. Ciprofloxicin was used as a standard drug for A. baumannii, while Amoxicillin was used as reference drug for E. coli, P. aeruginosa, S. aureus and P. vulgaris. Ampicillin was used as a standard antibiotic for VRSA, Rifampicin was used as a standard for M. morganii and DMSO (1%) was used as a negative control. Wells were made into agar medium and 50 µl of the test sample was delivered into them. All plates were examined for any zones of growth inhibition after 24 h incubation at 37°C and zone diameters were measured in millimeters.
Optimization of fermentation conditions and medium compositions for the production of chrysomycin a by a marine-derived strain Streptomyces sp. 891
Published in Preparative Biochemistry & Biotechnology, 2021
Hong-Jin Ni, Sun-Yan Lv, Ying-Tao Sheng, Hong Wang, Xiao-He Chu, Hua-Wei Zhang
Chrysomycins, one group of glycosides with benzonaphthopyranone structure, were firstly discovered from strain Streptomyces A-419 in 1955 and lately isolated from several other Streptomyces strains.[1–3] Biological assay had indicated that these compounds have significant anti-phage, anti-bacterial and anti-tumor activities.[4–6] Recently, chrysomycin A was shown to exhibit a strong inhibitory effect on drug-resistant pathogens including Mycobacterium tuberculosis.[7] Nowadays, the emergence of drug resistance in pathogenic microbes is one of the terrible and fatal threats to mankind. According to data by a British government report, the global cases of death caused by drug-resistant infection will annually reach up to 10 million and become the first killer as of 2050.[8] It is urgent to develop new antibiotics to conquer these pathogens. Previous pharmacological studies indicate the chrysomycin A possesses remarkable antimicrobial effects on drug-resistant G+ bacteria, such as methicillin-resistant Staphylococcus aureus, MRSA, Vancomycin resistant Staphylococcus aureus, VRE.[9] Therefore, this leading compound has great potential to be developed into a new theraputic agent to treat infectious diseases caused by drug-resistant pathogens. In order to produce enough quantity of chrysomycin A for drug evaluation, experiment on optimization of fermentation process was carried out in this work. Therefore, chrysomycin A as one of drug leads has great potential to be applied in the pharmaceutical industry. To the best of our knowledge, however, a report on the preparation process of chrysomycin A is unavailable so far, including optimization of fermentation, isolation and purification processes. Moreover, large-scale preparation of chrysomycin A is hard to be achieved owing to its low yield and complex components. In order to solve its problem, one wild-type chrysomycin A-producing Streptomyces sp. 891 from marine sediment was isolated and used as the starting strain in this work. Effects of various fermentation factors and medium constituents on the yield of chrysomycin A were carefully evaluated at shake-flask level, and these conditions were further optimized using orthogonal test design.