Bioengineered nisin A derivatives with enhanced activity against both Gram positive and Gram negative pathogens.

Bioengineered nisin A derivatives with enhanced activity against both Gram positive and Gram negative pathogens.
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DOI:
10.1371/journal.pone.0046884
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Ross RP
Ross RP
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Field D;Begley M;O'Connor PM;Daly KM;Hugenholtz F;Cotter PD;Hill C;Ross RP

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Nisin is a bacteriocin widely utilized in more than 50 countries as a safe and natural antibacterial food preservative. It is the most extensively studied bacteriocin, having undergone decades of bioengineering with a view to improving function and physicochemical properties. The discovery of novel nisin variants with enhanced activity against clinical and foodborne pathogens has recently been described. We screened a randomized bank of nisin A producers and identified a variant with a serine to glycine change at position 29 (S29G), with enhanced efficacy against S. aureus SA113. Using a site-saturation mutagenesis approach we generated three more derivatives (S29A, S29D and S29E) with enhanced activity against a range of Gram positive drug resistant clinical, veterinary and food pathogens. In addition, a number of the nisin S29 derivatives displayed superior antimicrobial activity to nisin A when assessed against a range of Gram negative food-associated pathogens, including E. coli, Salmonella enterica serovar Typhimurium and Cronobacter sakazakii. This is the first report of derivatives of nisin, or indeed any lantibiotic, with enhanced antimicrobial activity against both Gram positive and Gram negative bacteria.
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