Microscopic and metabolomics analysis of the anti-Listeria activity of natural and engineered cruzioseptins

IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sebastián Bermúdez-Puga , Meriellen Dias , Iara Lima Reis , Taciana Freire de Oliveira , Sonia Regina Yokomizo de Almeida , Maria Anita Mendes , Simon J. Moore , José R. Almeida , Carolina Proaño-Bolaños , Ricardo Pinheiro de Souza Oliveira
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Abstract

Listeria monocytogenes is a human opportunistic foodborne pathogen that produces life-threatening infections with a high mortality rate. The control of Listeria in the food production environment and effective clinical management of human listeriosis are challenging due to the emergence of antibiotic resistance. Hence we evaluate the in vitro anti-Listeria activity of two synthetic cruzioseptins reproducing their natural sequences CZS-9, and CZS-12, and one engineered sequence based on CZS-1, named [K4K15]CZS-1. The assessment of the in vitro potential of cruzioseptins, highlighted the promising antibacterial effect of [K4K15]CZS-1 in very low concentrations (0.91 μM) and its thermal stability at high-temperature conditions, is compatible with the food industry. Microscopic and metabolomic analyses suggest cruzioseptin induces anti-Listeria bioactivity through membrane disruption and changes in the intracellular metabolome. We also report that [K4K15]CZS-1 is not resistant to peptidases/proteases emphasizing a key advantage for their use as a food preservative. However, there is a need for further structural and functional optimisations for the potential clinical application as an antibiotic. In conclusion, [K4K15]CZS-1 stand out as membrane-active peptides with the ability to induce shifts in the bacteria metabolome and inspire the development of strategies for the prevention of L. monocytogenes emergence and dissemination.

对天然和工程克鲁斯肽抗李斯特菌活性的显微和代谢组学分析。
单核细胞增生李斯特菌是一种人类机会性食源性致病菌,可造成高死亡率的危及生命的感染。由于抗生素耐药性的出现,在食品生产环境中控制李斯特菌以及对人类李斯特菌病进行有效的临床治疗都面临着挑战。因此,我们评估了两种人工合成的克鲁斯肽的体外抗李斯特菌活性,这两种克鲁斯肽分别再现了它们的天然序列 CZS-9 和 CZS-12,以及一种基于 CZS-1 的工程序列,命名为 [K4K15]CZS-1。对胭脂虫肽体外潜力的评估突出表明,[K4K15]CZS-1 在极低浓度(0.91 μM)下具有良好的抗菌效果,而且在高温条件下具有热稳定性,可用于食品工业。显微镜和代谢组学分析表明,克柔塞肽可通过膜破坏和细胞内代谢组变化诱导抗李斯特菌生物活性。我们还报告说,[K4K15]CZS-1 对肽酶/蛋白酶具有抗性,这是其用作食品防腐剂的一个关键优势。不过,还需要进一步优化结构和功能,才能将其作为抗生素应用于临床。总之,[K4K15]CZS-1 是一种具有膜活性的多肽,能够诱导细菌代谢组的变化,有助于开发防止单核细胞增多症出现和传播的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biochimie
Biochimie 生物-生化与分子生物学
CiteScore
7.20
自引率
2.60%
发文量
219
审稿时长
40 days
期刊介绍: Biochimie publishes original research articles, short communications, review articles, graphical reviews, mini-reviews, and hypotheses in the broad areas of biology, including biochemistry, enzymology, molecular and cell biology, metabolic regulation, genetics, immunology, microbiology, structural biology, genomics, proteomics, and molecular mechanisms of disease. Biochimie publishes exclusively in English. Articles are subject to peer review, and must satisfy the requirements of originality, high scientific integrity and general interest to a broad range of readers. Submissions that are judged to be of sound scientific and technical quality but do not fully satisfy the requirements for publication in Biochimie may benefit from a transfer service to a more suitable journal within the same subject area.
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