Multidrug-resistant (MDR) superbugs can breach the blood–brain barrier (BBB), leading to a continuous barrage of pro-inflammatory modulators and induction of severe infection-related pathologies, including meningitis and brain abscess. Both broad-spectrum or species-specific antibiotics (β-lactamase inhibitors, polymyxins, vancomycin, meropenem, plazomicin, and sarecycline) and biocompatible poly (lactic-co-glycolic acid) (PLGA) nanoparticles have been used to treat these infections. However, new therapeutic platforms with a broad impact that do not exert off-target deleterious effects are needed. Membrane vesicles or extracellular vesicles (EVs) are lipid bilayer-enclosed particles with therapeutic potential owing to their ability to circumvent BBB constraints. Bacteria-derived EVs (bEVs) from gut microbiota are efficient transporters that can penetrate the central nervous system. In fact, bEVs can be remodeled via surface modification and CRISPR/Cas editing and, thus, represent a novel platform for conferring protection against infections breaching the BBB. Here, we discuss the latest scientific research related to gut microbiota- and probiotic-derived bEVs, and their therapeutic modifications, in terms of regulating neurotransmitters and inhibiting quorum sensing, for the treatment of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases. We also emphasize the benefits of probiotic-derived bEVs to human health and propose a novel direction for the development of innovative heterologous expression systems to combat BBB-crossing pathogens.

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 -β). 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.

Infections linked to Staphylococcus spp. are difficult to treat with current antibiotic therapy, resulting in increased antibiotic resistance populations. One of the leading strategies to overcome this issue is the novel combination of antibacterial nanoparticles (NPs) and sustainable natural compounds. This study reported the identification of a new synergistic combination of copper oxide (CuO) NPs, a well-known antibacterial agent against Staphylococcus spp., and anthraquinone-2-carboxylic acid (AQ), a plant-derived antimicrobial compound, with a potent and specific fashion in killing Staphylococcus spp. CuO NPs were synthesized using the one-pot coprecipitation method and characterized by using X-ray diffraction and transmission electron microscopy. Further checkerboard analysis showed that CuO NPs and AQ increased the antibacterial activity of individual agents against Staphylococcus aureus among Staphylococcus spp. by four- to eightfold compared to individual materials. Additional mechanistic studies on the synergy revealed that the inhibition of biofilm formation and loss of cytoplasmic volume with cell shrinkage are the major actions of the combination in expressing the phenotype. This study clearly showed that the combination of CuO NPs and AQ would be a novel strategy to eradicate S. aureus infections.