Study On The Antibacterial Effection Of Bi₂Te₃ Or Bi₂S₃ Nanospheres Combined With Antibiotic Against Multiresistant Staphylococcus Aureus

With the overuse of antibiotics and the emergence ofantibiotic-resistant bacteria,the drug-resistant bacteria infections therapies become more difficult and complicated.Traditional antibiotics cannot meet the requirements of treatments,moreover,the research and development of novel antimicrobial drugs cannot keep in pace withthe appearance of infectious diseases.Therefore,more and morepeople pay their attentions to develop new antimicrobial agents and take an active partin investigating new antibacterial treatments.The combination of antibiotics with another material is one of the effective methods to fight against drug resistant bacteria at present.In recent years,inorganic nano-materials become a new generation of antimicrobial agents because of their stable chemical properties,broad antimicrobial activity,and uneasy to produce drug resistance.Screening of combination of inorganic nano-materials with invalid antibiotics,and studying the synergistic mechanism will provide a way for the use of traditional antibiotics in the treatment of drug resistant bacteria.In this paper,the antibacterial activity of seven kinds of bismuth based nano-materials against E.coli and S.aureus was determined,and Bi₂S₃ nanospheres（NPs）and Bi₂Te₃ NPs appeared obvious antibacterial effects.The joint effects of the two nanomaterials with antibioticsagainst Methicillin-resistant staphylococcus aureus（MRSA）were investigated and the synergistic mechanisms were also studied.The results will provide new pathway for using traditional antibiotics to kill drug-resistant bacteria.The major research works were listed as following:（1）Screening the combination of bismuth nanomaterials with antibiotics which have synergistic antimicrobial activity against bacteria.The Bi₂S₃ and Bi₂Te₃ with obvious antibacterial activity against E.coli andS.aureus were selected from seven kinds bismuth nanomaterials by the methods of inhibition zone,minimum bacterial concentration and minimum bactericidal concentration to carry out further research.S.aureus,which are sensitive to five kinds of antibiotics and MRSA is resistant to them were screened out by antibiotic sensitivity tests.The antibacterial activity of Bi₂S₃ NPs and Bi₂Te₃ NPs combined with the five antibiotics were determined by the disk diffusion test,and the combinations of Bi₂S₃+GEN,Bi₂Te₃+CTX and Bi₂Te₃+CXM appeared synergistic effects.（2）Study on the synergistic mechanism of Bi₂S₃ and GEN against MRSA.The results of atomic force microscopy（AFM）observation and cellular potassium measurement indicated that Bi₂S₃ could destroy the membrane structure of MRSA,increasing membrane permeability,which can facilitate the entry of GEN into inner of bacteria and potentiate the activity of GEN against MRSA.Further study showed that Bi₂S₃ could induce the higher cellular amount of reactive oxygen species（ROS）,which was associated with the antibacterial effect.The cytotoxicity test indicated that the combination of Bi₂S₃ with GEN presented low cytotoxicity to human normal hepatocyte L02.（3）Study on the synergistic mechanism of Bi₂Te₃ and CTX against MRSA.The results of AFM observation and intracellular potassium content showed that Bi₂Te₃ NPs could destroy the structure of the bacterial membrane,increasing the permeability of the cell membrane.In addition,the cells could produce a large amount of ROS,which lead to the death of the bacteria.Bi₂Te₃ inhibited the activity of β-lactamase in MRSA,thereby,it would reduce the resistance of MRSA to CTX.Similarly,the cytotoxicity test indicated that the combination of Bi₂Te₃ with CTX presented low cytotoxicity to human normal hepatocyte L02.