The emergence of multidrug-resistant (MDR) bacterial infections poses a catastrophic threat to medicine. The development of phage-based therapy combined with antibiotics might be an advantageous weapon in the arms race between human and MDR bacteria. A cocktail composed of the MDR Acinetobacter baumannii infecting bacteriophages with high lytic activity was used in combination with antibiotics to destroy a bacterial biofilm in human urine. A. baumannii exhibited varying susceptibility to the host range of bacteriophages used in this study, ranging from 56% to 84%. This study demonstrated that bacteriophages could reduce biofilm biomass in a human urine model, and some of the antibiotics commonly used in the treatment of urinary tract infection (UTI) act synergistically with phage cocktails. Additionally, the combined treatment showed a significantly greater reduction of biofilm biomass and clearance of persister cells.
The novel approach for deposition of iron oxide nanoparticles with narrow size distribution supported on different sized graphene oxide was reported. Two different samples with different size distributions of graphene oxide (0.5 to 7 mum and 1 to 3 mum) were selectively prepared, and the influence of the flake size distribution on the mitochondrial activity of L929 with WST1 assay in vitro study was also evaluated. Little reduction of mitochondrial activity of the GO-Fe3O4 samples with broader size distribution (0.5 to 7 mum) was observed. The pristine GO samples (0.5 to 7 mum) in the highest concentrations reduced the mitochondrial activity significantly. For GO-Fe3O4 samples with narrower size distribution, the best biocompatibility was noticed at concentration 12.5 mug/mL. The highest reduction of cell viability was noted at a dose 100 mug/mL for GO (1 to 3 mum). It is worth noting that the chemical functionalization of GO and Fe3O4 is a way to enhance the biocompatibility and makes the system independent of the size distribution of graphene oxide.
Increasing multidrug resistance has led to renewed interest in phage-based therapy. A combination of the bacteriophages and antibiotics presents a promising approach enhancing the phage therapy effectiveness. First, phage candidates for therapy should be deeply characterized. Here we characterize the bacteriophage vB_AbaP_AGC01 that poses antibacterial activity against clinical Acinetobacter baumannii strains. Moreover, besides genomic and phenotypic analysis our study aims to analyze phage–antibiotic combination effectiveness with the use of ex vivo and in vivo models. The phage AGC01 efficiently adsorbs to A. baumannii cells and possesses a bacteriolytic lifecycle resulting in high production of progeny phages (317 ± 20 PFU × cell−1). The broad host range (50.27%, 93 out of 185 strains) against A. baumannii isolates and the inability of AGC01 to infect other bacterial species show its high specificity. Genomic analysis revealed a high similarity of the AGC01 genome sequence with that of the Friunavirus genus from a subfamily of Autographivirinae. The AGC01 is able to significantly reduce the A. baumannii cell count in a human heat-inactivated plasma blood model (HIP-B), both alone and in combination with antibiotics (gentamicin (GEN), ciprofloxacin (CIP), and meropenem (MER)). The synergistic action was observed when a combination of phage treatment with CIP or MER was used. The antimicrobial activity of AGC01 and phage-antibiotic combinations was confirmed using an in vivo larva model. This study shows the greatest increase in survival of G. mellonella larvae when the combination of phage (MOI = 1) and MER was used, which increased larval survival from 35% to 77%. Hence, AGC01 represents a novel candidate for phage therapy. Additionally, our study suggests that phages and antibiotics can act synergistically for greater antimicrobial effect when used as combination therapy.
1 September 2020 in Biochemical Engineering Journal
The aim of this study was to analyse the effect of rotating magnetic field (RMF) exposition on the fungal laccase catalytic properties. The results obtained in the study revealed that RMF may positively alter the laccase activity. A significant increase in activities of 11%, 11%, and 9% were observed at 10 Hz, 40 Hz and 50 Hz, respectively. Exposure of laccase to the rotating magnetic field resulted in its increased activity at broader pH range and a slight shift in optimum pH from 4.0 to 4.5 at RMF with frequency 20 Hz. The results show that the enzyme activity, stability, and optimum pH can be significantly altered depending on the characteristic of the applied RMF. Application of rotating magnetic field opens a new way for controlling and directions of enzyme-based bioprocessing.