Furan-based Chalcone Annihilates the Multi-Drug-Resistant Pseudomonas aeruginosa and Protects Zebra Fish Against its Infection.

The emergence of carbapenem-resistant Pseudomonas aeruginosa, a multi-drug-resistant bacteria, is becoming a serious public health concern. This bacterium infects immunocompromised patients and has a high fatality rate. Both naturally and synthetically produced chalcones are known to have a wide array of biological activities. The antibacterial properties of synthetically produced chalcone were studied against P. aeruginosa. In vitro, study of the compound (chalcone derivative named DKO1), also known as (2E)-1-(5-methylfuran-2-yl)-3-(4-nitrophenyl) prop-2-en-1-one, had substantial antibacterial and biofilm disruptive action. DKO1 effectively shielded against P. aeruginosa-induced inflammation, oxidative stress, lipid peroxidation, and apoptosis in zebrafish larvae. In adult zebrafish, the treatment enhanced the chances of survivability and reduced the sickness-like behaviors. Gene expression, biochemical analysis, and histopathology studies found that proinflammatory cytokines (TNF-α, IL-1ß, IL-6, iNOS) were down regulated; antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) levels increased, and histoarchitecture was restored in zebrafish. The data indicate that DKO1 is an effective antibacterial agent against P. aeruginosa demonstrated both in vitro and in vivo.

Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro, ex-vivo and in-vivo studies.

The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

A Study of the Virulence Traits of Carbapenem-Resistant Klebsiella pneumoniae Isolates in a Galleria mellonella Model.

The increasing incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains is considered as a terrifying public health concern. This study target was to gain a further insight into the virulence traits of CRKP isolates in Egypt. The study was carried out by using 43 clinical K. pneumoniae isolates. Antibiotic susceptibility testing, biofilm formation assay, and molecular characterization of carbapenemase and virulence genes were done for all isolates. In addition, the genotypic relationship between CRKP isolates was identified by using enterobacterial repetitive intergenic consensus-polymerase chain reactions (ERIC-PCRs). A Galleria mellonella survival assay was adopted for in vivo testing of virulence of the CRKP. Carbapenem resistance was exhibited among 58% (25/43) isolates. Minimum inhibitory concentration values of carbapenem-resistant K. pneumoniae (CRKP) ranged from 32 to 128 µg/mL. Biofilm assay has revealed that 21 isolates (49%) had moderate biofilm formation and 11 isolates (25.5%) were strong biofilm producers. BlaNDM-1 was recognized in 20.9% (9/43) of the isolates, while blaOXA-48 was observed in 18.5% (8/43). Type 3 fimbriae (mrkD) and entB were addressed among 72.1% and 62.8% of K. pneumoniae isolates, respectively. The ybtS and iutA genes were detected among 44.2% and 37.2% of the isolates, respectively. ERIC-PCR showed 23 genetic profiles among CRKP isolates. CRKP biofilm producers were virulent according to the G. mellonella model, which indicates the importance of biofilm as a virulence trait among CRKP. This study indicates the emergence of CRKP with increased virulence traits, especially biofilm formation, in Egypt. This alarming report highlights the ongoing need for effective screening procedures and strict infection control measures.