Stapled Phd Peptides Inhibit Doc Toxin Induced Growth Arrest in Salmonella.

Stapled Phd Peptides Inhibit Doc Toxin Induced Growth Arrest in Salmonella.
复制标题

钉合Phd肽抑制沙门氏菌中Doc毒素诱导的生长停滞。

DOI:
10.1021/acschembio.3c00411
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发表时间:
2023-12-15
影响因子:
4
通讯作者:
Barnard, Anna
Barnard, Anna
中科院分区:
生物学2区
文献类型:
--
作者:
Worm, Dennis J.;Grabe, Grzegorz J.;de Castro, Guilherme V.;Rabinovich, Sofya;Warm, Ian;Isherwood, Kira;Helaine, Sophie;Barnard, Anna

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细菌毒素抑制是克服抗生素失效的一种有前途的方法。在沙门氏菌中,已经证明敲除毒素Doc可以显著减少耐药持续菌的形成。Doc是一种激酶,在非耐受细胞中被其同源抗毒素Phd抑制。在这项工作中,我们已经开发了一流的钉合肽抗毒素模拟物的基础上博士博士的文件抑制序列。在进行一系列取代以改善细菌摄取后,我们鉴定了能够抵消沙门氏菌中Doc毒性的铅钉Phd肽。这为进一步开发能够降低病原菌中抗生素持久性的治疗肽提供了一个令人兴奋的起点。
Bacterial toxin inhibition is a promising approach to overcoming antibiotic failure. InSalmonella, knockout of the toxin Doc has been shown to significantly reduce the formation of antibiotic-tolerant persisters. Doc is a kinase that is inhibited in nontolerant cells by its cognate antitoxin, Phd. In this work, we have developed first-in-class stapled peptide antitoxin mimetics based on the Doc inhibitory sequence of Phd. After making a series of substitutions to improve bacterial uptake, we identified a lead stapled Phd peptide that is able to counteract Doc toxicity in Salmonella. This provides an exciting starting point for the further development of therapeutic peptides capable of reducing antibiotic persistence in pathogenic bacteria.
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