Glycyrrhetinic Acid Decreases The Expression Of Staphylococcus Aureus α-toxin And Impacts The Pathogenicity Of Staphylococcus Aureus Both In Vitro And In Vivo

Staphylococcus aureus is a commonly seen, gram-positive bacteria and ahospital-associated and community-associated opportunistic pathogen. Generally, S.aureus colonize in the nasal cavity of otherwise healthy people, when the immunesystem is compromised, S. aureus begin to proliferate and infect host tissue. S. aureusinfection in animals may cause cattle and sheep gangrenous mastitis and cow breastinfection such as cystitis, leading serious damage to animal husbandry. S. aureuspneumonia ranks the second S. aureus associated disease. Staphylococcus aureuspneumonia incidence rate was highest among people with immune-suppressiondiseases patients, and patients receiving immunosuppressive therapy. Its incidence inpatients with influenza and tracheal intubation in patients was also quite amazing.More seriously, Staphylococcus aureus pneumonia mortality rate is extremely high,the mortality rate is high up to24%-50%, in all bacterial pneumonia is the highest.The emergence of methicillin-resistant Staphylococcus aureus makes it even moredifficult for the prevention and control of Staphylococcus aureus. The development ofthe antibiotic resistance of Staphylococcus aureus and the stagnation of traditionalantibiotic development make the treatment of Staphylococcus aureus infection evenmore difficult. Therefore, searching for new antibacterial mechanism, as well asdeveloping novel antibiotics in the new mechanism of is imminent. Such as resistanceto bacterial adhesion, resistance to bacterial communication, and resistance tobacterial virulence factors of the treatment strategy appeal the interest of the majorityof scientific researchers. Especially, the treatment strategie of resistance to bacterialvirulence factors is the priority concern.Staphylococcus aureus can secrete a large number of pathogenic virulence factors.Thevirulence factors include coagulase, adhesion, DNase, hemolytic toxin, enterotoxin,exotoxins, enzyme and biofilm. Staphylococcus aureus enterotoxin causes food poisoning; TSST-1is a superantigen causing the body shock; food poisoning causedby Staphylococcus aureus enterotoxin; while the a-hemolysin of is the mainpathogenic factor of staphylococcus aureus pneumonia.Staphylococcus aureus can produce a variety of membrane damaginghemolysins.According to their antigenicity, they can be divided into alpha-, beta-, gamma-,delta-toxin, in which a-hemolysin is the major pathogenic toxin. A-hemolysin is apore-forming toxin. It can lyse many kinds of human cells. A-hemolysin is animportant virulence factor of Staphylococcus aureus infection. At the same time, thea-hemolysin has good antigenicity, and it is highly conserved in Staphylococcusaureus strains. Therefore, the a-hemolysin is of great importance for the study ofdrugs against Staphylococcus aureus infectionIn this study, I first determined the effect of glycyrrhetinic acid, the main componentsof licorice, on the growth of Staphylococcus aureus. I found that glycyrrhetinic acidhad no inhibitory effect the growth of Staphylococcus aureus. We then performedexperiments and analysis such as Western blotting and fluorescence quantitative PCR,and confirmed that glycyrrhetinic acid can reduce the Staphylococcus aureusa-hemolysin secretion. We also found that glycyrrhetinic acid reduced the expressionlevel of a-hemolysin gene hla and the regulatory gene agr. The results demonstratedthat glycyrrhetinic acid could decrease the expression level of HLA and agr, thusmaking expression of a-hemolysin decline. Glycyrrhetinic acid was added intoStaphylococcus aureus/lung epithelial cells co-culture system. By detection of damageof A549cells through live/dead test and LDH assay, we found glycyrrhetinic acid canreduce Staphylococcus aureus damage on human lung epithelial A549cells. Animalexperiments show that glycyrrhetinic acid can reduce Staphylococcus aureuspneumonia mortality rate, alleviate the lung lesions in mice with Staphylococcusaureus pneumonia and reduce the secretion of inflammatory factor. Glycyrrhetinicacid has a significant protective effect on mice with Staphylococcus aureuspneumonia.