Baicalin Attenuates Panton-Valentine Leukocidin (PVL)-Induced Cytoskeleton Rearrangement via Regulating the RhoA/ROCK/LIMK and PI3K/AKT/GSK-3ß Pathways in Bovine Mammary Epithelial Cells.

Pore-forming toxins (PFTs) exert physiological effects by rearrangement of the host cell cytoskeleton. Staphylococcus aureus-secreted PFTs play an important role in bovine mastitis. In the study, we examined the effects of recombinant Panton-Valentine leukocidin (rPVL) on cytoskeleton rearrangement, and identified the signaling pathways involved in regulating the process in bovine mammary epithelial cells (BMECs) in vitro. Meanwhile, the underlying regulatory mechanism of baicalin for this process was investigated. The results showed that S. aureus induced cytoskeleton rearrangement in BMECs mainly through PVL. S. aureus and rPVL caused alterations in the cell morphology and layer integrity due to microfilament and microtubule rearrangement and focal contact inability. rPVL strongly induced the phosphorylation of cofilin at Ser3 mediating by the activation of the RhoA/ROCK/LIMK pathway, and resulted in the activation of loss of actin stress fibers, or the hyperphosphorylation of Tau at Ser396 inducing by the inhibition of the PI3K/AKT/GSK-3ß pathways, and decreased the microtubule assembly. Baicalin significantly attenuated rPVL-stimulated cytoskeleton rearrangement in BMECs. Baicalin inhibited cofilin phosphorylation or Tau hyperphosphorylation via regulating the activation of RhoA/ROCK/LIMK and PI3K/AKT/GSK-3ß signaling pathways. These findings provide new insights into the pathogenesis and potential treatment in S. aureus causing bovine mastitis.

Correlation between bacterial extracellular vesicles and antibiotics: A potentially antibacterial strategy.

Bacterial extracellular vesicles (BEVs) are proteoliposome nanoparticles that are secreted by both Gram-negative (G-) and Gram-positive (G+) bacteria. BEVs have significant roles in various physiological processes of bacteria, including driving inflammatory responses, regulating bacterial pathogenesis, and promoting bacterial survival in diverse environments. Recently, there has been increasing interest in the use of BEVs as a potential solution to antibiotic resistance. BEVs have shown great promise as a new approach to antibiotics, as well as a drug-delivery tool in antimicrobial strategies. In this review, we provide a summary of recent scientific advances in BEVs and antibiotics, including BEV biogenesis, ability to kill bacteria, potential for delivering antibiotics, and their role in the development of vaccines or as immune adjuvants. We propose that BEVs provide a novel antimicrobial strategy that would be beneficial against the increasing threat of antibiotic resistance.