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Investigating anti-biofilm and anti-persister activities of natural compounds and antimicrobial proteins
Title
Investigating anti-biofilm and anti-persister activities of natural compounds and antimicrobial proteins
Creator
Jin, Xing
Date
2020
Description
Bacterial biofilm formation is frequently involved in the development of chronic infectious diseases. Inhibiting biofilms is challenging due...
Show moreBacterial biofilm formation is frequently involved in the development of chronic infectious diseases. Inhibiting biofilms is challenging due to their tolerance against conventional antibiotics which are not effective to penetrating biofilm matrix to kill the cells residing in biofilms. Metabolically dormant cells known as persisters are also not eradicated by antibiotic treatment. Therefore, novel antimicrobial drugs that can kill non-growing persisters or inhibit biofilms are needed urgently. Here, we investigate the anti-biofilm and anti-persister activities of new drug candidates including plant extracts, fatty acids and colicins. We firstly screened 50 different plant extracts on enterohemorrhagic E. coli and Listeria monocytogenes, and identified Cancavalia ensiformis-derived lectin Concanavalin A (ConA) inhibits biofilm formation of enterohemorrhagic E. coli and Listeria monocytogenes by binding to carbohydrates on bacterial cell surface. Biofilm results support that ConA lectin can be applied for developing anti-adherent and anti-biofilm agents to control biofilms. Also, fatty acids may be promising candidates as anti-persister or anti-biofilm agents, because some fatty acids exhibit antimicrobial effects. We screened a fatty acid library consisting of 65 different fatty acid molecules for altered persister formation. We found that undecanoic acid, lauric acid, and N-tridecanoic acid inhibited E. coli persister cell formation including enterohemorrhagic E. coli EDL933. These fatty acids were all medium chain saturated forms. Furthermore, the fatty acids repressed EHEC biofilm formation (for example, by 8-fold for lauric acid) without having antimicrobial activity. This study demonstrates that medium chain saturated fatty acids can serve as anti-persister and anti-biofilm agents that may be applied to treat bacterial infections. Colicins, a type of antimicrobial bacteriocins, are considered as a viable alternative of conventional antibiotics due to their unique cell killing mechanisms that can damage cells by pore-forming on the cell membrane, nuclease activity, and cell wall synthesis inhibition. In this study, we utilized cell-free protein synthesis to produce colicins with different modes of action. We optimized the production yield and activity of colicins in cell-free system. Also, we tested effect of cell-free produced colicins on persister cell formation and biofilm formation. We illustrated that colicins kill persister cells and biofilm cells. Moreover, colicins produced from the engineered probiotic E. coli cells, which can be used as a living medicine, specifically and significantly eradicate target biofilms without affecting other bacterial population. Colicins have great potential to be an antibiotic alternative, and engineered probiotic E. coli is a potential candidate for engineered bacterial therapeutics.
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