Construction Of Effective Antimicrobialagent Of Bovine Serum Albumin Based On PH Response

New antimicrobial agents based on macromolecular architecture have been widely focused for their better antibacterial ability compared with traditional antibiotic.High molecular polymer is usually utilized as the matrix in macromolecular antimicrobial agents.However,it is difficult to be biocompatible and to degrade,limiting the applications of macromolecular antimicrobial agents significantly.Therefore,this study constructed a protein-based antibacterial?BSA-GAa-m PEG?which introduced the p H regulation mechanism,improving the biocompatibility of antibacterial agent and figuring out the problem of bacterial resistance that traditional antibiotic could not solve.It provided a new approach for the design of macromolecule antibacterial agent and a solution for the treatment of drug-resistant strain infection.In this paper,bovine serum albumin?BSA?was used as the biological protein matrix to construct the basic skeleton,which was endowed with antibacterial ability through the introduction of guanidine group.Then we obtained the antimicrobial agent BSA-GAa-m PEG with p H response ability and better biocompatibility obtained through the wrapping of polyethylene glycol.The BSA-NH₂-GAa has excellent physicochemical properties due to its strong positive potential and nanoscale size,which enables the protein-based biological complex antibacterial agent excellent antibacterial properties against Escherichia coli?Gram-negative bacteria?and Staphylococcus aureus?Gram-positive bacteria?.Conventional commercial antibiotics can make bacteria resistant to them,but BSA-NH₂-GAa can effectively prevent bacteria from developing drug resistance.BSA-GAa-m PEG wrapped by m PEG shows good biocompatibility and can reduce hemolysis to fresh rabbit blood?red blood cells?and cytotoxicity to mouse embryonic fibroblasts?mammalian cells?.m PEG and BSA-NH₂-GAa were linked by aldehyde group and amino group to form controllable Schiff bond.BSA-GAa-m PEG was capable of being anti-bacterial against E.coli and S.aureus under the condition of p H=5.6.Finally we explored the antibacterial mechanism of BSA-GAa-m PEG towards bacterial.BSA-GAa-m PEG connected with bacterial through electrostatic interaction,which was proven by Zeta potential,and the bacterial cell membrane breakage and intracellular solution flow observed by scanning electron microscopy?SEM?caused the death of bacterial,resulting in no bacterial drug resistance because bacteria can't develop resistance to this antibacterial factor.