Screening Anti-virulence Activity Of 50 Medicinal And Edrble Plants On Salmonella And Studies On The Anti-virulence Activity Of Two Plants

Antibiotics have become a powerful weapon in the prevention and treatment of bacterial infectious diseases,saving countless lives.Meanwhile,the resistance of pathogens to antibiotics has become a public problem all over the world.In recent years,the research and development of anti-virulence drugs has become the forefront of research on anti-pathogenic infection drugs.The anti-virulence drugs attenuate or inhibit pathogenic bacterial infection by inhibiting the virulence factors.Type ?secretion system is therefore emerging as a very attractive target for antimicrobial drugs.In recent years,many anti-virulence natural products have been discovered from medicinal plants,therefore,medicinal plants are a valuable resource for discovering natural anti-virulence molecules with unique structures and diverse types.This thesis focus on the Salmonella Typhimurium and its T3SS to carry out three aspects studies:1)50 Myanmar medicinal and edible plant extracts were screened for their anti-T3SS activity;2)the chemical constituents of Ficus virens(MMV203);3)the protective effects of the active fraction of Cinnamomum bejolghota(My 104)on Salmonella-infected mice.Chapter 1 provided a summary of the structure and function of the bacterial type III secretion system and the pathogenicity of Salmonella through a literature search.And there also presents a brief overview of T3SS inhibitors of natural compounds that found in recent years according to different structural types.Chapter 2 the anti-T3SS activity of 50 Myanmar medicinal and edible plants were screened.Six of them[Spondias pinnata(MMV-65),Ficus chartacea(MMV-87-2),Ludwigia adscendens(MMV-125),Acacia pennata(MMV-128),Neptunia plena(MMV-133)and Ficus virens(MMV-203)]were found to have good inhibitory effect on the T3SS secretion proteins of SipA,SipB,SipC,SipD,without effecting the growth of S.Typhimurium.Chapter 3 the chemical constituents of F.virens leaves were isolated by anti-T3SS acvitity guided method.Three compounds were elucidated including a new disaccharide ester compound(1),one tri-unsaturated fatty acid(2)and one diglyceride(3).Compounds 2 and 3 showed significant inhibitory effects on the secretion of T3SS virulence proteins.Chapter 4 presented the successful model of the Salmonella-infected Kunming mice by intragastric administration,and the active Fr.A of C.bejolghota bark showed protective effect on Salmonella-infected Kunming mice by changes in body weight and organ index etc.In summary,this thesis suggested that Myanmar medicinal and edible plants are important resources for searching of anti-T3SS inhibitors.The active constituents of F.virens was identified,and the protective effect of C.bejolghota on infected mice was verified,which laying a foundation for anti-virulence drug discovery and development of Myanmar plants.