Research On Bacterial Membrane Control Method Based On Aptamer Targeted Delivery Technology

Salmonella enterica serovar Typhimurium(S.typhimurium)is an important enteric pathogen causing gastroenteritis,bacteremia and diarrhea in a wide range of species.It causes significant morbidity,mortality,and economic burden in worldwide,no matter in high-income or impoverished nations.While the routine treatment of salmonellosis commonly using antibiotics,Salmonella spp.are able to attach and subsequently proliferate,mature and form sessile communities known as biofilm,as it renders the pathogen highly tolerant to host immune systems,disinfectants and unless a lethal doses of antibiotics,consequently more prone to generate antibiotic resistant infections.Although S.typhimurium is a well studied organism in terms of biofilm formation,no drugs,as of right now,can cure and eradicate the biofilm.For the reasons mentioned above,it is urgent to explore new antibiofilm drugs for us.(1)In this work,the impacts of bacteriostatic aptamer and graphene oxide(GO)on different stages of biofilm were preliminary studied,and the key goal is to synthesis an aptamer-modified GO conjugate in controlling biofilm.GO and aptamer ST-3 had shown a clear antibiofilm ability,when GO was targeted by ST-3,93.5% S.typhimurium biofilm was inhibited and 84.6% was dispersed.It is also clarified that the efficacies of the biofilm inhibition and removal by the conjugate are significantly greater than that of ST-3,GO or the mixture of the two.Therefore,it is proposed that ST-3 facilitated GO into the protective barrier made by dead cells,and decreased the cellular membrane potential to prevent their growth at same time.This innovative antibiofilm material can avoid the abuse of antibiotics and help combat the rise of antibiotic resistance,which offers a tremendous opportunity for potential applications in biomedical and clinical microbiology fields.(2)Cocktail therapy with multi-drugs has been widely used in various diseases treatment,also achieved affirmable curative effect.We evaluated the effects and mechanism of Lactoferrin(LF)on biofilm formation and mature biofilm.It was showed that LF had a mild antibiofilm activity,and the iron-withholding ability is its core mechanism.When iron-free LF(apo-LF)was used in combination with GO,ST-3 or ST-3-GO,it was found that associated treatment of antibiofilm materials and apo-LF significantly reduced the amounts of biofilm compared with the level of reduction achieved with each agent alone no matter in biofilm inhibition and dispersal assays.What is more,the combination of apo-LF and ST-3-GO in the treatment of mature biofilm could effectively shorten the course of treatment.These results demonstrate the potential usefulness of drug cocktails for the prevention and treatment of biofilm related diseases.Sophisticated drug cocktail,that is pathogen-specific and composed of various novel antibiofilm agents,may well be routinely applied to treat biofilm-associated infections in the future.