The Anti-anaerobic Bacteria Activity Evaluation Of Natural Products And Drug Combination Study Against Clostridium Difficile

The original report of Clostridium difficile which was identified as part of the neonatal flora by Hall and O’Tolle was published in 1935.C.difficile was initially unnoticed,until it was associated with pseudomembranous colitis caused by long-term antibiotic treatment in 1978.In recent years,there have been frequent outbreaks of Clostridium difficile infection(CDI)with rising infection rates and mortality rates in North America and Europe,which seriously threatens global public health.The highly toxic and multi-drug resistant strain 027/B1/NAP1 is the main epidemic strain in North America and Europe,but it has recently been detected in Chinese hospitals as well.In order to better prevent and control CDI,on the one hand,the government needs to introduce regulatory measures for the use of antibiotics;on the other hand,it’s an urgent need to develop new antibiotics against highly toxic and multi-drug resistant strains.In this thesis,to search for new antibiotics,we have screened a compound collections including our in-house natural product library(～3000 compounds)from marine microorganism from the southeast coast and reported bioactive compound library(～350 compounds)against C.difficile,with the hits rate of 3.9%and 6.9%,respectively.Followed by systematic evaluation of the antibacterial and bactericidal activities of the ’hits’.Our results revealed that the’hit’,compound B1 has superior bactericidal activity against C.difficile.The optimal activity of compound B1 was achieved after half hour treatment at a concentration of 0.015μg/mL.Further combination study of compound B1 with other antibiotics was carried out.The results revealed that compound B1 has excellent synergistic effect with philamycin,tirapazamine and vancomycin.In summary,we have successfully identified a series of bioactive compounds against C.difficile from our in-house natural products collection.The synergistic effect was achieved with the combination of B1 and known antibiotics.These results provide leads for development of new drugs against C.difficile and laid the foundation for C.difficile management and treatment.