Characterization of Increased Extracellular Vesicle-Mediated Tigecycline Resistance in Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is the most detrimental pathogen that causes hospital-acquired infections. Tigecycline (TIG) is currently used as a potent antibiotic for treating CRAB infections; however, its overuse substantially induces the development of resistant isolates. Some molecular aspects of the resistance mechanisms of AB to TIG have been reported, but they are expected to be far more complicated and diverse than what has been characterized thus far. In this study, we identified bacterial extracellular vesicles (EVs), which are nano-sized lipid-bilayered spherical structures, as mediators of TIG resistance. Using laboratory-made TIG-resistant AB (TIG-R AB), we demonstrated that TIG-R AB produced more EVs than control TIG-susceptible AB (TIG-S AB). Transfer analysis of TIG-R AB-derived EVs treated with proteinase or DNase to recipient TIG-S AB showed that TIG-R EV proteins are major factors in TIG resistance transfer. Additional transfer spectrum analysis demonstrated that EV-mediated TIG resistance was selectively transferred to Escherichia coli, Salmonella typhimurium, and Proteus mirabilis. However, this action was not observed in Klebsiella pneumonia and Staphylococcus aureus. Finally, we showed that EVs are more likely to induce TIG resistance than antibiotics. Our data provide direct evidence that EVs are potent cell-derived components with a high, selective occurrence of TIG resistance in neighboring bacterial cells.

A Review of Immunomodulatory Reprogramming by Probiotics in Combating Chronic and Acute Diabetic Foot Ulcers (DFUs).

Diabetic foot ulcers (DFUs) are characterized by a lack of angiogenesis and distal limb diabetic neuropathy. This makes it possible for opportunistic pathogens to protect the biofilm-encased micro-communities, causing a delay in wound healing. The acute and chronic phases of DFU-associated infections are distinguished by the differential expression of innate proinflammatory cytokines and tumor necrosis factors (TNF-α and -ß). Efforts are being made to reduce the microbial bioburden of wounds by using therapies such as debridement, hyperbaric oxygen therapy, shock wave therapy, and empirical antibiotic treatment. However, the constant evolution of pathogens limits the effectiveness of these therapies. In the wound-healing process, continuous homeostasis and remodeling processes by commensal microbes undoubtedly provide a protective barrier against diverse pathogens. Among commensal microbes, probiotics are beneficial microbes that should be administered orally or topically to regulate gut-skin interaction and to activate inflammation and proinflammatory cytokine production. The goal of this review is to bridge the gap between the role of probiotics in managing the innate immune response and the function of proinflammatory mediators in diabetic wound healing. We also highlight probiotic encapsulation or nanoformulations with prebiotics and extracellular vesicles (EVs) as innovative ways to tackle target DFUs.