School of Microbiology, University College Cork, T12 K8AF Cork, Ireland.
APC Microbiome Ireland, T12 YT20 Cork, Ireland.
Int J Mol Sci. 2021 Mar 27;22(7):3480. doi: 10.3390/ijms22073480.
Bovine mastitis is a significant economic burden for dairy enterprises, responsible for premature culling, prophylactic and therapeutic antibiotic use, reduced milk production and the withholding (and thus wastage) of milk. There is a desire to identify novel antimicrobials that are expressly directed to veterinary applications, do not require a lengthy milk withholding period and that will not have a negative impact on the growth of lactic acid bacteria involved in downstream dairy fermentations. Nisin is the prototypical lantibiotic, a family of highly modified antimicrobial peptides that exhibit potent antimicrobial activity against many Gram-positive microbes, including human and animal pathogens including species of and . Although not yet utilized in the area of human medicine, nisin is currently applied as the active agent in products designed to prevent bovine mastitis. Over the last decade, we have harnessed bioengineering strategies to boost the specific activity and target spectrum of nisin against several problematic microorganisms. Here, we screen a large bank of engineered nisin derivatives to identify novel derivatives that exhibit improved specific activity against a selection of staphylococci, including mastitis-associated strains, but have unchanged or reduced activity against dairy lactococci. Three such peptides were identified; nisin A M17Q, nisin A T2L and nisin A HTK.
奶牛乳腺炎是奶业企业的重大经济负担，可导致奶牛提前淘汰、预防性和治疗性使用抗生素、产奶量减少以及（因此造成）牛奶被扣留（和浪费）。人们渴望找到专门针对兽医应用的新型抗菌药物，这些抗菌药物不需要长时间的扣留牛奶期，并且不会对下游乳制品发酵中涉及的乳酸菌的生长产生负面影响。乳链菌肽是典型的细菌素，是一类经过高度修饰的抗菌肽，对许多革兰氏阳性菌具有强大的抗菌活性，包括人类和动物病原体，包括 和 等物种。虽然尚未在人类医学领域中使用，但乳链菌肽目前作为活性成分应用于旨在预防奶牛乳腺炎的产品中。在过去的十年中，我们利用生物工程策略来提高乳链菌肽针对几种有问题的微生物的特异性活性和靶向谱。在这里，我们筛选了大量工程化乳链菌肽衍生物，以鉴定出对一系列葡萄球菌（包括乳腺炎相关菌株）表现出提高的特异性活性但对乳制品乳球菌的活性不变或降低的新型衍生物。鉴定出三种这样的肽；乳链菌肽 A M17Q、乳链菌肽 A T2L 和乳链菌肽 A HTK。
