A Family of Antibiotics That Evades Resistance by Binding Polyprenyl Phosphates.
A Family of Antibiotics That Evades Resistance by Binding Polyprenyl Phosphates.
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通过结合聚异戊二烯磷酸酯来逃避耐药性的抗生素家族。
DOI：
10.1021/acsinfecdis.3c00475
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发表时间：
2023
影响因子：
5.3
通讯作者：
Brady,SeanF
中科院分区：
文献类型：
--
作者：
Rosenzweig,AdamF;Wang,Zongqiang;Morales-Amador,Adrián;Spotton,Kaylyn;Brady,SeanF
Cilagicin 是一种革兰氏阳性活性抗生素，具有双重聚异戊二烯磷酸酯结合机制，可阻止耐药性的发展。在这里，我们通过生物信息学筛选了预测的非核糖体多肽合成酶编码结构，以寻找同样可以避免耐药性发展的抗生素。我们确定的预测结构的合成和生物活性筛选产生了三种对多重耐药革兰氏阳性病原体具有活性的抗生素，其中两种，类青霉素和维吉拉霉素，即使在长时间接触抗生素后也不会导致耐药性。
Cilagicin is a Gram-positive active antibiotic that has a dual polyprenyl phosphate binding mechanism that impedes resistance development. Here we bioinformatically screened predicted non-ribosomal polypeptide synthetase encoded structures to search for antibiotics that might similarly avoid resistance development. Synthesis and bioactivity screening of the predicted structures that we identified led to three antibiotics that are active against multidrug-resistant Gram-positive pathogens, two of which, paenilagicin and virgilagicin, did not lead to resistance even after prolonged antibiotic exposure.