Bacterial invasion into eukaryotic cells and the establishment of intracellular infection has proven to be an effective means of resisting antibiotic action, as anti‐infective agents commonly exhibit a poor permeability across the host cell membrane. Encapsulation of anti‐infectives into nanoscaled delivery systems, such as liposomes, is shown to result in an enhancement of intracellular delivery. The aim of the current work is, therefore, to formulate colistin, a poorly permeable anti‐infective, into liposomes suitable for oral delivery, and to functionalize these carriers with a bacteria‐derived invasive moiety to enhance their intracellular delivery. Different combinations of phospholipids and cholesterol are explored to optimize liposomal drug encapsulation and stability in biorelevant media. These liposomes are then surface‐functionalized with extracellular adherence protein (Eap), derived from Staphylococcus aureus. Treatment of HEp‐2 and Caco‐2 cells infected with Salmonella enterica using colistin‐containing, Eap‐functionalized liposomes resulted in a significant reduction of intracellular bacteria, in comparison to treatment with nonfunctionalized liposomes as well as colistin alone. This indicates that such bio‐invasive carriers are able to facilitate intracellular delivery of colistin, as necessary for intracellular anti‐infective activity. The developed Eap‐functionalized liposomes, therefore, present a promising strategy for improving the therapy of intracellular infections.

Ureteral catheters are indispensable devices used in the management of ureteral obstruction. Although the stent is essential for treatment, it also has complications, which are encrustation, stone formation and biofilm formation. Biofilm infections result in a complication in the course of treatment, increasing the length of patients stay in hospital and overall cost. Catheter-associated infections are difficult to be treated with antibiotics and there is a need to change catheters due to the formation of biofilm on their surfaces. In this study, In this study, we examine the effect of some of prescribed drugs as NSAIDs and N-acetylcysteine on the adherence of S. aureus, K. pneumoniae, P. aeruginosa and Proteus mirabilis on the surface of catheters, and their effects on the preformed mature biofims. Also, we determine their antibacterial activity. The results showed that the tested agents had good antibacterial activity, a significant effect on the inhibition of adherence of the tested strains to plastic surfaces and a high disruptive effect on mature biofilms. In conclusion, the tested drugs can be used in the treatment of catheterassociated infections.

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When searching for new antibiotics against Gram-negative bacterial infections, a better understanding of the permeability across the cell envelope and tools to discriminate high from low bacterial bioavailability compounds are urgently needed. Inspired by the phospholipid vesicle-based permeation assay (PVPA), which is designed to predict non-facilitated permeation across phospholipid membranes, outer membrane vesicles (OMVs) of Escherichia coli either enriched or deficient of porins are employed to coat filter supports for predicting drug uptake across the complex cell envelope. OMVs and the obtained in vitro model are structurally and functionally characterized using cryo-TEM, SEM, CLSM, SAXS, and light scattering techniques. In vitro permeability, obtained from the membrane model for a set of nine antibiotics, correlates with reported in bacterio accumulation data and allows to discriminate high from low accumulating antibiotics. In contrast, the correlation of the same data set generated by liposome-based comparator membranes is poor. This better correlation of the OMV-derived membranes points to the importance of hydrophilic membrane components, such as lipopolysaccharides and porins, since those features are lacking in liposomal comparator membranes. This approach can offer in the future a high throughput screening tool with high predictive capacity or can help to identify compound-and bacteria-specific passive uptake pathways.