Study On Screening For Extracts Of Plant And Endophytes Against Drug-resistant Bacteria And Identification Of Active Components

Bacteria have been developing resistances to antimicrobial agents rapidly for years. The emergence of methicillin-resistant Staphylococcus aureus (MRSA) strains, penicillin-resistant Stareptococcus pneumoniae (PRSP)strains, multidrug-resistant Mycobacterium tuberculosis strains and vancomycin-resistant enterococci strains, have resulted in serious problems in treating infectious diseases. It is difficult to deal with drug-resistant bacteria by the antimicrobial agents being used for a long time. At present, screening for new antimicrobial compounds against drug-resistant bacteria is a hotspot of pharmacology. In order to develop new antimicrobial agent combating to drug-resistant bacteria, the subject of this test included that establishing the extracts libraries, screening for antimicrobial extracts from libraries by targeting to the bacterial cells, bacterial efflux pumps, andβ-lactamase, identifying the active single chemical entities and components by bioassay-guided isolation.The secondary metabolites of plants and endophytes are a vast natural pool of compounds and a main source which new drugs derived from. The crude extract libraries in this test are consisted of 300 samples extracted from plants and endophytes.The methods of Kirby-Barer disc agar diffusion and drug–base agar were used to screen the crude extract libraries against the resistant strains of S. aureus, P. aeruginosa and K. pneumoniae isolated from clinical patients. The mycelium extract of M.erythraea Sh.Et Dodge exhibited powerful antimicrobial activities. Bioassay-guided isolation of the mycelium extract of M.erythraea by TLC and column chromatography, a single chemical entity with antimicrobial activities, named compound 1, was purified. Compound 1 was identified as a kind of steroid compound by 1H, 13C NMR spectra and high solvable mass spectrometry. The compound 1 inhibited 9 strains of bacteria at the MICs ranges from 8 to 128μg/ml. It was more powerful against G+ bacteria than G- bacteria. It inhibited the resistant and sensitive stains of S. aureus at same concentrations, and probably the different strains shared same target of compound 1. In order to test the anti-infection activities of compound 1 in vivo, mice were infected with resistant strains of S. aureus, P. aeruginosa and K. pneumoniae. Compound 1 could prevent mice from death and the livability at the ranges 70 to 100% with obvious concentration-reponse relationships. Compound 1 belongs to steroid compound, and no toxicity to be found (selective index >7). It is valuable to modify the compound 1, being...