Epidemiological Analysis And Drug Resistance Characteristics Of Staphylococcus Aureus Causing Bloodstream Infections In Patient And Screening Of Filamentous Temperature-sensitive Protein Z Inhibitors

Part 1Objective To investigate the infection characteristics and drug resistance of Staphylococcus aureus causing bloodstream infections in patients so as to provide a new method for the treatment of infections.Methods A total of 81 clinical isolates of Staphylococcus aureus were collected from whole blood specimen,from 2016 to 2018 per year.All isolates SA and drug sensitivity test were identified,identified by the VITEK2 automatic microorganism analyze and disk diffusion method.Results Among the81 samples,65.43%(53/81)patients were caused by MRSA.The main detection rate of MRSA specimens were originated from neonates 47.17 %(25/53)and infants24.50%(13/53)in neonatal ward,surgical system and emergency and critical care department.All or most of Staphylococcus aureus were resistant to peniciliin,oxacillin,erythromycin,clindamycin,oxacillin and norfloxacin,but entirely sensitive to linezolid and vancomycin.The resistance of MRSA to 13 antibiotics or combined antibiotics was higher than that of MSSA.Conclusion MRSA has been become the main strain of Staphylococcus aureus causing bloodstream infections in patient of the hospital.The resistance rate of MRSA toward various antibiotics was higher than that of MSSA.The analysis shows that the rational usage of antibiotics is important.Furthermore,we should monitor the resistance of antibiotics while Staphylococcus aureus causing bloodstream infections in patientPart 2Objective To investigate novel antimicrobial agents targeting Filamentous temperature-sensitive protein Z(Fts Z).Methods Identification of potential molecules targeting Fts Z by structural-based virtual screening by Discovery Studio 2017 R2 software in a variety of ways.Determination of antibacterial effect against S.aureus of small molecules by broth dilution method.Molecular dynamics simulation was used to evaluate the binding stability of small molecules with Fts Z protein.Results Fifty molecules with potential drug ability and excellent binding ability with Fts Z were obtained by virtual screening.All compounds exhibit certain antimicrobial effects to MSSA or MRSA.Among them,compound 5010-0572 showed best activity against MSSA and MRSA,with MIC value of 1?g/ml.Molecular dynamics simulation illustrated that compound 5010-0572 with best antimicrobial effects bound to Fts Z better than compound C592-0444 with lowest antimicrobial effects.Conclusion The antimicrobial effects of small molecules targeting Fts Z was closely related to the binding stability with protein.Compound 5010-0572,which has notable antimicrobial activity,might become a leading compound for the development of new antimicrobial agent.