Effect Of Radix Paeoniae Rubra On Antibiotic Sensitivity And Pathogenicity Of MRSA ST-59 Strain

Staphylococcus aureus is an important zoonotic pathogen,which can cause extremely high morbidity and mortality after infecting animals.In particular,the emergence and prevalence of multi-drug resistant S.aureus MRSA has made antibiotics a great challenge in the treatment of anti-bacterial infections.Therefore,the development of new antibiotic alternatives has become the main research direction.Some studies have found that Chinese medicine has a significant effect in the treatment of bacterial infections,and it also has the effect of delaying and reversing bacterial resistance.Our previous study found that the aqueous extract of Radix Paeoniae Rubra has the effect of inhibiting the growth of S.aureus and reducing cell damage,excellent results.In this study,the effects of Radix Paeoniae Rubra on bacterial drug sensitivity and toxin secretion were studied by in vitro experiments,and the effects of combination of Radix Paeoniae Rubra and antibiotics on pneumonia in mice infected with MRSA ST-59 were investigated by in vivo experiments.The analysis of the genomics of S.aureus by aqueous extract of Radix Paeoniae Rubra showed that the differential sRNA target gene was adjusted after 5 hours of aqueous extract of Radix Paeoniae Rubra,and the number of adjustment was increased with the increase of concentration.Cluster analysis revealed that these genes are involved in proliferation,bacterial infection,bacterial resistance,cell cycle,and the like.Signal pathway analysis revealed that Radix Paeoniae Rubra can interfere with the expression of S.aureus cell cycle and bacterial resistance-related genes.The results indicated that the aqueous extract of Radix Paeoniae Rubra had an effect on various biological functional genes of Staphylococcus aureus ATCC-29213.Using microdilution method to detect the sensitivity of S.aureus MRSA ST-59 to different antibiotics,it was found that MRSA ST-59 against lincomycin,azithromycin,chloramphenicol,linezolid,doxycycline hydrochloride,ciprofloxacin hydrochloride Stars are resistant.When combined with the aqueous extract of Radix Paeoniae Rubra,it was found that the growth activity of S.aureus decreased significantly with the increase of the concentration of aqueous extract of Radix Paeoniae Rubra,which was significantly different from the control group with antibiotics alone.The difference is that MRSA ST-59 is sensitive to antibiotics such as rifampicin and gentamicin.After administration of antibiotics,it can inhibit the survival rate of bacteria.When combined with the aqueous extract of Radix Paeoniae,it increases the survival rate of bacteria.The results showed that the antibiotic resistance of MRSA-ST59 strain could be improved by the combination of antibiotics with sub-inhibitory concentration and aqueous extract of Radix Paeoniae Rubra at sub-inhibitory concentration.Western blot analysis of sub-inhibitory concentration of Radix Paeoniae Rubra aqueous extract and sub-inhibitory concentration of antibiotics on the expression of MRSA-ST59 virulence factors HLα,SEA,SEB,SPA showed that the combination of Radix Paeoniae Rubra at sub-inhibitory concentration and 32 μg/mL antibiotics has a good inhibitory effect on the expression of MRSA ST-59 virulence factors HLα,SEA,SEB and SPA.The results indicate that the concentration of erythraea in thesub-inhibitory concentration is antibiotics with sub-inhibitory concentration.After combination,the expression levels of MRSA-ST59 virulence factors HLα,SEA,SEB and SPA can be significantly reduced,which has the effect of reducing the pathogenicity of MRSA-ST59.After the mice were infected by the nasal drop method to establish a mouse pneumonia infection model,the Radix Paeoniae Rubra was combined with the antibiotic lincomycin,and the histological examination and lung bacteria content were detected in the lungs of the mice 3 and 7 days after the administration.The expression levels of S.aureus HLα,SEA,SEB and SPA were measured by Western blot.The results indicate that the combination of the sub-inhibitory concentration of Radix Paeoniae Rubra aqueous extract and the sub-inhibitory concentration of lincomycin can significantly reduce the pathogenicity of MRSA-ST59 in mice,reduce the damage of lung tissue in mice.The above results suggest that the combination of the sub-inhibitory concentration of Radix Paeoniae Rubra aqueous extract and the sub-inhibitory concentration of antibiotics can significantly improve sensitivity of MRSA ST-59 against lincomycin,azithromycin,chloramphenicol,linezolid,doxycycline hydrochloride and ciprofloxacin hydrochloride,the antibiotic can effectively play an antibacterial effect at the sub-inhibitory concentration,and at the same time,the expression of the MRSA ST-59 toxin protein can be reduced to reduce the pathogenicity of the bacteria and reduce the tissue damage in infected parts of animals.