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具有增强抗革兰氏阳性和革兰氏阴性病原体活性的生物工程化乳链菌肽 A 衍生物。

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

机构信息

Department of Microbiology, University College Cork, Cork, Ireland.

出版信息

PLoS One. 2012;7(10):e46884. doi: 10.1371/journal.pone.0046884. Epub 2012 Oct 8.

DOI:10.1371/journal.pone.0046884
PMID:23056510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3466204/
Abstract

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.

摘要

尼辛是一种广泛应用于 50 多个国家的细菌素,被用作安全且天然的抗菌食品防腐剂。它是研究最多的细菌素之一,经过数十年的生物工程改造,旨在改善其功能和物理化学性质。最近描述了新型尼辛变体的发现,这些变体对临床和食源性病原体具有增强的活性。我们筛选了随机的尼辛 A 生产者库,并鉴定出一个在 29 位丝氨酸到甘氨酸发生改变的变体(S29G),对金黄色葡萄球菌 SA113 的功效增强。我们使用定点饱和突变方法生成了另外三个衍生物(S29A、S29D 和 S29E),它们对一系列革兰氏阳性耐药临床、兽医和食品病原体具有增强的活性。此外,当评估一系列革兰氏阴性与食品相关的病原体,包括大肠杆菌、肠炎沙门氏菌血清型 Typhimurium 和阪崎克罗诺杆菌时,一些尼辛 S29 衍生物对尼辛 A 的抗菌活性优于尼辛 A。这是第一个报道的具有增强抗革兰氏阳性和革兰氏阴性细菌活性的尼辛或任何类细菌素衍生物的报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf4/3466204/83ec967fe5c7/pone.0046884.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf4/3466204/f3e000fbf739/pone.0046884.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf4/3466204/dbbee0ab8638/pone.0046884.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf4/3466204/214395016018/pone.0046884.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf4/3466204/dda0400518ba/pone.0046884.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf4/3466204/83ec967fe5c7/pone.0046884.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf4/3466204/f3e000fbf739/pone.0046884.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf4/3466204/dbbee0ab8638/pone.0046884.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf4/3466204/214395016018/pone.0046884.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf4/3466204/dda0400518ba/pone.0046884.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caf4/3466204/83ec967fe5c7/pone.0046884.g005.jpg

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