过表达二葡糖基二乙酰甘油合成酶会导致枯草芽孢杆菌产生达托霉素抗性。

IF 2.7 3区 生物学 Q3 MICROBIOLOGY
Journal of Bacteriology Pub Date : 2024-10-24 Epub Date: 2024-09-05 DOI:10.1128/jb.00307-24
Ryogo Yamamoto, Kazuya Ishikawa, Yusuke Miyoshi, Kazuyuki Furuta, Shin-Ichi Miyoshi, Chikara Kaito
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引用次数: 0

摘要

脂肽类抗生素达托霉素通过与细胞膜上的磷脂酰甘油(PG)和脂质 II 形成复合物,导致细胞膜穿孔,从而对革兰氏阳性细菌具有杀菌活性。随着达托霉素耐药细菌的出现,了解细菌对达托霉素的耐药机制变得非常重要。在这项研究中,我们旨在确定导致革兰氏阳性杆菌模型枯草芽孢杆菌产生达托霉素耐药性的遗传因素。我们的研究结果表明,过表达编码二葡糖基二乙酰甘油合成酶的 ugtP 会诱导枯草芽孢杆菌产生达托霉素抗性。具体来说,过表达 ugtP 会导致二葡糖基二乙酰甘油(Glc2DAG)水平升高,酸性磷脂心磷脂和 PG 以及碱性磷脂溶血磷脂酰甘油水平降低。然而,ugtP 的过表达并没有改变细胞表面电荷和对阳离子抗菌肽 nisin 或阳离子表面活性剂十六烷基三甲基溴化铵的敏感性。此外,通过在有达托霉素存在的情况下进行连续传代,我们获得了携带 ugtP 突变的耐达托霉素突变体。这些突变体的 Glc2DAG 水平增加,达托霉素的最小抑制浓度增加了 4 倍以上。这些结果表明,在 ugtP 过表达的驱动下,Glc2DAG 水平的增加改变了磷脂的组成,并在不改变细菌细胞表面电荷的情况下赋予了枯草杆菌对达托霉素的耐药性。了解达托霉素耐药的机制对于建立针对达托霉素耐药细菌的临床对策非常重要。在本研究中,我们发现编码二葡糖基二乙酰甘油合成酶的 ugtP 过表达会诱导革兰氏阳性菌模型--枯草杆菌产生达托霉素耐药性。UgtP 的过表达增加了二葡糖基二乙酰甘油的水平,导致磷脂组成改变和达托霉素抗性。这些发现对于制定针对耐达托霉素细菌的临床策略,包括检测和管理这些细菌非常重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Overexpression of diglucosyldiacylglycerol synthase leads to daptomycin resistance in Bacillus subtilis.

The lipopeptide antibiotic daptomycin exhibits bactericidal activity against Gram-positive bacteria by forming a complex with phosphatidylglycerol (PG) and lipid II in the cell membrane, causing membrane perforation. With the emergence of daptomycin-resistant bacteria, understanding the mechanisms of bacterial resistance to daptomycin has gained great importance. In this study, we aimed to identify the genetic factors contributing to daptomycin resistance in Bacillus subtilis, a model Gram-positive bacterium. Our findings demonstrated that overexpression of ugtP, which encodes diglucosyldiacylglycerol synthase, induces daptomycin resistance in B. subtilis. Specifically, overexpression of ugtP resulted in increased levels of diglucosyldiacylglycerol (Glc2DAG) and decreased levels of acidic phospholipids cardiolipin and PG, as well as the basic phospholipid lysylphosphatidylglycerol. However, ugtP overexpression did not alter the cell surface charge and the susceptibility to the cationic antimicrobial peptide nisin or the cationic surfactant hexadecyltrimethylammonium bromide. Furthermore, by serial passaging in the presence of daptomycin, we obtained daptomycin-resistant mutants carrying ugtP mutations. These mutants showed increased levels of Glc2DAG and a >4-fold increase in the minimum inhibitory concentration of daptomycin. These results suggest that increased Glc2DAG levels, driven by ugtP overexpression, modify the phospholipid composition and confer daptomycin resistance in B. subtilis without altering the cell surface charge of the bacteria.IMPORTANCEDaptomycin is one of the last-resort drugs for the treatment of methicillin-resistant Staphylococcus aureus infections, and the emergence of daptomycin-resistant bacteria has become a major concern. Understanding the mechanism of daptomycin resistance is important for establishing clinical countermeasures against daptomycin-resistant bacteria. In the present study, we found that overexpression of ugtP, which encodes diglucosyldiacylglycerol synthase, induces daptomycin resistance in B. subtilis, a model Gram-positive bacteria. The overexpression of UgtP increased diglucosyldiacylglycerol levels, resulting in altered phospholipid composition and daptomycin resistance. These findings are important for establishing clinical strategies against daptomycin-resistant bacteria, including their detection and management.

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来源期刊
Journal of Bacteriology
Journal of Bacteriology 生物-微生物学
CiteScore
6.10
自引率
9.40%
发文量
324
审稿时长
1.3 months
期刊介绍: The Journal of Bacteriology (JB) publishes research articles that probe fundamental processes in bacteria, archaea and their viruses, and the molecular mechanisms by which they interact with each other and with their hosts and their environments.
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