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The therapeutic potential of phages has been considered since their first identification more than a century ago. The evident concept of using a natural predator to treat bacterial infections has, however, since then been challenged considerably. Initially, the vast success of antibiotics almost eliminated the study of phages for therapy. Upon the renaissance of phage therapy research, the most provocative and unique properties of phages such as high specificity, self-replication and co-evolution prohibited a rapid preclinical and clinical development. On the one hand, the typical trajectory followed by small molecule antibiotics could not be simply translated into the preclinical analysis of phages, exemplified by the need for complex broad spectrum or personalized phage cocktails of high purity and the more complex pharmacokinetics. On the other hand, there was no fitting regulatory framework to deal with flexible and sustainable phage therapy approaches, including the setup and approval of adequate clinical trials. While significant advances are incrementally made to eliminate these hurdles, phage-inspired antibacterials have progressed in the slipstream of phage therapy, benefiting from the lack of hurdles that are typically associated with phage therapy. Most advanced are phage lytic enzymes that kill bacteria through peptidoglycan degradation and osmotic lysis. Both phages and their lytic enzymes are now widely considered as safe and have now progressed to clinical phase II to show clinical efficacy as pharmaceutical. Yet, more initiatives are needed to fill the clinical pipeline to beat the typical attrition rates of clinical evaluation and to come to a true evaluation of phages and phage lytic enzymes in the clinic.

The unprecedented dissemination of antibiotic resistance announces a close post antibiotic era, thus exploring effective alternatives is urgent. Natural products are untapped alternatives that could offer effective alternatives with low costs. Sparastolonin B (SsnB) is a natural anthracene-derivative with a reported anti-inflammatory activity; however, its potential antibacterial activity is still under-explored. Here, we investigated both antibacterial and anti-inflammatory activity of SsnB in vitro , in vivo and in silico. In vitro, SsnB showed a specific antibacterial activity against Gram-positive bacteria with MIC range of 1–4 µg/ml against S. aureus and E. faecalis . Furthermore, it displayed a profound antibacterial activity against the clinical MRSA strain K15 in both wound infection, and peritonitis infection models with overall bacterial count reductions up to 1.21 and 1.23 log-units respectively. In addition, it has significantly improved wound healing and tissue repair rates compared to the un-treated group in wound infection model. SsnB has also significantly down-regulated the expression of inflammatory mediators, TLR-2, MCP-1, CXCL-1, CXCL-2, IL-6 and IL-1β, in the treated rabbits highlighting its potential anti-inflammatory activity. Finally, in silico analysis has predicted Gyr-B as a potential target for the observed SsnB antibacterial activity. To conclude, SsnB is a promising natural compound with a dual antibacterial and anti-inflammatory activities, suggesting it as a good candidate for subsequent clinical investigation.

Background In nosocomial settings, vancomycin-resistant Enterococcus faecalis is a major health threat leading to increased morbidities, mortalities, and treatment costs. Nowadays, several approaches are under investigation to enhance the activity of or replace the traditional antibiotics. Bacteriophage therapy was sought as a potential approach for combating E. faecalis infections. The present study focuses on isolating and characterizing bacteriophage against clinical multi-drug resistant (MDR) E. faecalis strain Lb-1492. The phage stability, lytic activity, host-range, latent period, burst size, the ability to detach the pre-formed biofilm and destroy entrapped cells were investigated. The phage genome was purified, sequenced, and subjected to bioinformatics analysis for identifying and characterizing its features, as well as, the suitability for clinical application. Finally, the ability of the phage to rescue mice from deadly, experimentally induced E. faecalis bacteremia was evaluated. Results A virulent phage was isolated from sewage water against a clinical MDR E. faecalis isolate. Morphological and genomic studies indicated that the phage belongs to the Efquatrovirus genus, with a long tail, icosahedral head and a linear double-stranded DNA genome of approximately 42.9 kbp. The phage was named vB _Efa_ZAT1 (shortly ZAT1). It demonstrated a shorter latent period and larger burst size than regular-tailed phages, and a characteristic stability over a wide range of pH and temperatures, with the optimum activity at pH 7.4 and 37 °C, respectively. Phage ZAT1 showed a narrow spectrum of activity and a characteristic biofilm disruption ability. The phage managed successfully to control E. faecalis -induced bacteremia in mice models, which was lethal within 48 h in the control group. An intraperitoneal injection of 3 × 10 8 PFU of the phage solution given 1 h after the bacterial challenge was sufficient to save all the animals, completely reversing the trend of 100% mortality caused by this bacterium. Conclusions Phage therapy can be a promising alternative to traditional antibiotics in the post-antibiotic era with a significant antimicrobial and antibiofilm activities against MDR E. faecalis .

Background Successful treatment of pathogenic bacteria like Enterobacter Cloacae with bacteriophage (phage) counteract some hindrance such as phage stability and immunological clearance. Our research is focused on the encapsulation of phage HK6 within chitosan nanoparticles. Result Encapsulation significantly improves stability, efficacy, and delivery of phages. Chitosan nanoparticles (CS-NPs) achieve a phage entrapment efficiency of 97%. Fourier-transform infrared spectroscopy (FT-IR) reveals shifts towards higher wavenumbers and a new peak, indicating amide bond formation and successful phage encapsulation. The average particle sizes for CS-NP and phage HK6 encapsulated CS-NPs were 180 ± 10 nm and 297 ± 18 nm, respectively. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) analyses reveal that phage HK6 encapsulated CS-NPs are larger on average than CS-NPs, highlighting successful phage encapsulation. Encapsulated bacteriophages maintain its effectiveness at higher pH levels of 11 and 12. Both encapsulated and free bacteriophages are thermostable between 25 and 60 °C; while at higher temperatures (up to 80 °C), the encapsulated phage is thermally stable. Over four days, 70.57% of phages were released from encapsulated CS-NPs. Encapsulation of bacteriophage HK6 in CS-NPs enhances antibacterial activity within the first 2 h, compared to phage or nanoparticles alone. Conclusion This suggests that the phage HK6 encapsulated CS-NPs exhibit potentiality as biocontrol agents against resistant microorganisms offering an alternative to phage alone. Graphical Abstract

Background Increased prevalence of Enterobacter cloacae within food products underscores food as an underexplored reservoir for antibiotic resistance, thus requiring particular intervention. Bacteriophages have been explored as a promising approach for controlling bacterial growth in different matrices. Moreover, their specific interaction and self-replication, put them apart from traditional methods for controlling bacteria in different matrices. Methods Sixteen Enterobacter cloacae strains were recovered from raw chicken. These strains were used to isolate bacteriophages using enrichment protocol. The broad-spectrum bacteriophage was evaluated in terms of thermal, pH, shearing stress and storge. Moreover, its infection kinetics, in vitro antibacterial activity, cytotoxicity were also assessed. Genomic sequencing was performed to exclude any potential virulence or resistance genes. Finally, the capability of the isolated phages to control bacterial growth in different chicken samples was assessed alone and in combination with sodium nitrite. Results The lytic bacteriophage vB_EclM_HK6 was isolated and showed the broadest spectrum being able to infect 8/16 E. cloacae strains with a lytic activity against its host strain, E. cloacae EC21, as low as MOI of 10 –6 . The phage displays a latent period of 10 min and burst size of 115 ± 44 and resistance frequency of 5.7 × 10 –4  ± 3.0 × 10 –4 . Stability assessment revealed a thermal tolerance up to 60 ˚C, wide range pH stability (3–10) and the ability to withstand shearing stress up to 250 rpm. HK6 shows no cytotoxicity against oral epithelial cells up to 10 12 PFU/ml. Genomic analysis revealed a Strabovirus with total size of 177,845 bp that is free from known resistance and virulence genes. Finally, HK6 pretreatment of raw chicken, chicken nuggets and ready-made cheese salad shows a reduced bacterial count up to 4.6, 2.96 and 2.81 log-units, respectively. Moreover, combing HK6 with sodium nitrite further improved the antibacterial activity in both raw chicken and chicken nuggets without significant enhancement in case of cheese salad. Conclusion Enterobacter bacteriophage vB_EclM_HK6 presents a safe and effective approach for controlling E. cloacae contaminating stored chicken food samples. Moreover, they could be combined with a reduced concentrations of sodium nitrite to improve the killing capacity.

The four-wheel-drive electric vehicle's traction chain is powered by four permanent-magnet synchronous motors (PMSM), powered by a single three-phase, five-leg inverter (FLI). In order to achieve the behavior of a mechanical differential and to require the parallel wheel-motors to turn at identical or different speeds, using this structure, an independent control is applied on each driving wheel. For this particular structure, there is a shared inverter leg between the two phases of two machines. The other two phases of each machine are attached to their own two inverter legs. This work's main focus is the suggestion of a new DTC technique for the control of an electric vehicle (EV) with two set bi-PMSM motor-wheels fed in parallel by a single three-phase five-leg inverter. The simulation results show that this new control technique can ensure excellent dynamics of the electric vehicle driving system.

Increased prevalence of Enterobacter cloacae within food products underscores food as an underexplored reservoir for antibiotic resistance, thus requiring particular intervention. Bacteriophages have been explored as a promising approach for controlling bacterial growth in different matrices. Moreover, their specific interaction and self-replication, put them apart from traditional methods for controlling bacteria in different matrices. Sixteen Enterobacter cloacae strains were recovered from raw chicken. These strains were used to isolate bacteriophages using enrichment protocol. The broad-spectrum bacteriophage was evaluated in terms of thermal, pH, shearing stress and storge. Moreover, its infection kinetics, in vitro antibacterial activity, cytotoxicity were also assessed. Genomic sequencing was performed to exclude any potential virulence or resistance genes. Finally, the capability of the isolated phages to control bacterial growth in different chicken samples was assessed alone and in combination with sodium nitrite. The lytic bacteriophage vB_(E)clM_(H)K6 was isolated and showed the broadest spectrum being able to infect 8/16 E. cloacae strains with a lytic activity against its host strain, E. cloacae EC21, as low as MOI of 10.sup.-6. The phage displays a latent period of 10 min and burst size of 115 [+ or -] 44 and resistance frequency of 5.7 x 10.sup.-4 [+ or -] 3.0 x 10.sup.-4. Stability assessment revealed a thermal tolerance up to 60 [degrees]C, wide range pH stability (3-10) and the ability to withstand shearing stress up to 250 rpm. HK6 shows no cytotoxicity against oral epithelial cells up to 10.sup.12 PFU/ml. Genomic analysis revealed a Strabovirus with total size of 177,845 bp that is free from known resistance and virulence genes. Finally, HK6 pretreatment of raw chicken, chicken nuggets and ready-made cheese salad shows a reduced bacterial count up to 4.6, 2.96 and 2.81 log-units, respectively. Moreover, combing HK6 with sodium nitrite further improved the antibacterial activity in both raw chicken and chicken nuggets without significant enhancement in case of cheese salad. Enterobacter bacteriophage vB_(E)clM_(H)K6 presents a safe and effective approach for controlling E. cloacae contaminating stored chicken food samples. Moreover, they could be combined with a reduced concentrations of sodium nitrite to improve the killing capacity.

Due to the fast, emerging development of antibiotic-resistant bacteria, the need for novel, efficient routes to battle these pathogens is crucial; in this scenario, metal-organic frameworks (MOFs) are promising materials for combating them effectively. Herein, a novel Cu-MOF—namely 1—that displays the formula [Cu3L2(DMF)2]n (DMF = N,N-dimethylformamide) is described, synthesized by the combination of copper(II) and 3,4-dihydroxybenzoic acid (H3L)—both having well-known antibacterial properties. The resulting three-dimensional structure motivated us to study the antibacterial activity, adsorptive capacity and processability of the MOF in the form of pellets and membranes as a proof-of-concept to evaluate its future application in devices.

Background The dissemination of multi-drug-resistant bacteria, particularly Methicillin-resistant Staphylococcus aureus (MRSA), necessitates exploring new alternatives for their control. Bacteriophages are promising antibiotic alternatives with unique features. Here, we have performed a comprehensive characterization of a newly isolated bacteriophage (PSK) and compared its therapeutic potential with vancomycin in vivo. Methods Sewage samples were processed and enriched with the MRSA S. aureus SK1 strain in a search for isolation of a lytic bacteriophage. The isolated bacteriophage was assessed in vitro in terms of thermal and pH stability and kinetic parameters using absorption and one step growth curve assays. Moreover, its potential antibacterial activity was evaluated against S. aureus SK1 lone and in combination of standard of care antibiotics used for treatment of wound infections. We further analyzed its genome to exclude the presence of any potential toxin or antibiotic resistance genes. Finally, its antibacterial potential and capability to alleviate wound infection were assessed using a murine wound-infection model. Results The lytic bacteriophage (PSK) was isolated as a new species of the genus Rosenblumvirus with a genome size of 17,571 bp that is free from potential resistance or virulence genes. PSK displays infectivity against 4/10 S. aureus strains including two vancomycin-resistant strains. Moreover, it demonstrates favorable infection kinetics of fast adsorption with latent period and burst size of 20 min and 123 PFU/infected cell, respectively. Stability analysis revealed thermal stability up to 60 °C with wide pH range stability (4–11). In vitro, PSK kills S. aureus SK1 with multiplicity of infection (MOI) as low as 10 − 4 with an overall mutation frequency of 2.47 × 10 − 6 CFU/mL that is further improved when combined with 0.25× MIC of oxacillin, fusidic acid or vancomycin. In vivo, a single dose of PSK in murine wound infection model exhibited a comparable performance to four doses of vancomycin, when treatment started 2 h post-infection. However, when applied 2 days post-infection, PSK demonstrates superior antibacterial activity (up to 4.58 log unit count reduction) and enhances wound closure and tissue healing. Conclusion These findings represent PSK as a potential vancomycin alternative effective in treating S. aureus - induced wound infections.

In this paper, we present the results of the gamma irradiation method to obtain N-doped mesoporous activated carbons. Nitrogen-enriched mesoporous carbons were prepared from three chosen commercial activated carbons such as Carbon Black OMCARB C-140, KETJENBLACK EC-600JD and PK 1-3 Norit. HRTEM, SEM, Raman spectra, elemental analysis, XPS studies and widely approved N2 adsorption–desorption measurements allowed us to evaluate the effectiveness of N atom insertion and its influence on the BET surface area and the pore structure of modified carbons. The obtained materials have an exceptionally high N content of up to 3.2 wt.%. Additionally, selected N-doped activated carbons were fully characterized to evaluate their applicability as carbon electrode materials with particular emphasis on Oxygen Reduction Reaction (ORR). The proposed method is a relatively facile, efficient and universal option that can be added to the already known methods of introducing heteroatoms to different carbons.