Gallic acid exerts antibiofilm activity by inhibiting methicillin-resistant Staphylococcus aureus adhesion.

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious threat to patients with nosocomial infections, and infection is strongly associated with biofilm formation. Gallic acid (GA) is a natural bioactive compound found in traditional Chinese medicines that exerts potent antimicrobial activity. However, the anti-MRSA biofilm efficacy of GA remained to be determined. This study investigated the antimicrobial activities of GA against MRSA and the mechanisms involved. The results revealed the significant antibacterial and antibiofilm activities of GA. The minimal inhibitory concentration of GA against MRSA was 32 µg/mL and a growth curve assay confirmed the significant inhibitory effect of GA on planktonic MRSA. Crystal violet and XTT assays showed that 8 µg/mL GA effectively inhibited the formation of new biofilms and disrupted existing biofilms by reducing both biofilm biomass and metabolic activities. Alkaline phosphatase and ß-galactosidase leakage assays and live/dead staining provided evidence that GA disrupted the integrity of bacterial cell walls and membranes within the biofilm. Scanning electron microscopy observations showed that GA significantly inhibited bacterial adhesion and aggregation, affecting the overall structure of the biofilm. Bacterial adhesion, polysaccharide intercellular adhesion (PIA) production and real-time quantitative PCR assay confirmed that GA inhibited bacterial adhesion, PIA synthesis, and the expression of icaAD and sarA. These results suggested that GA inhibited biofilm formation by inhibiting the expression of sarA, then downregulating the expression of icaA and icaD, thereby reducing the synthesis of PIA to attenuate the adhesion capacity of MRSA. GA is therefore a promising candidate for development as a pharmaceutical agent for the prevention and treatment of bacterial infections caused by MRSA.

Bradykinin induces acute kidney injury after hypothermic circulatory arrest through the repression of the Nrf2-xCT pathway.

Postoperative acute kidney injury (AKI) is a common complication in patients undergoing deep hypothermic circulatory arrest (HCA); however, its underlying pathogenesis is unclear. In this study, we established a rat cardiopulmonary bypass model and demonstrated that hypothermia during HCA, rather than circulatory arrest, was responsible for the occurrence of AKI. By recruiting 56 patients who underwent surgery with HCA and analyzing the blood samples, we found that post-HCA AKI was associated with an increase in bradykinin. Animal experiments confirmed this and showed that hypothermia during HCA increased bradykinin levels by increasing kallikrein expression. Mechanistically, bradykinin inhibited the Nrf2-xCT pathway through B2R and caused renal oxidative stress damage. Application of Icatibant, a B2R inhibitor, reversed changes in the Nrf2-xCT pathway and oxidative stress damage. Finally, Icatibant reversed hypothermia-induced AKI in vivo. This finding reveals the pathogenesis of AKI after HCA and helps to provide therapeutic strategy for patients with post-HCA AKI.