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内蒙农大:植物乳杆菌P-8适应抗生素时发生了什么变化

时间:2020-03-20 11:09来源:热心肠日报 作者:祁玉丽 浏览次数:
    1.在为期12个月的实验室适应性进化实验中,氨苄西林对植物乳杆菌P-8的最低抑菌浓度逐渐升高,最后达到细菌适应度的最大值;

    2.适应氨苄西林的菌株,在碳、氨基酸和细胞表面相关的代谢途径上发生了变化;

    3.基因敲除突变体证明6个基因的高表达有助于对氨苄西林耐药性;

    4.ATP-依赖性Clp蛋白酶/ ATP结合亚基ClpL、一个小的热休克蛋白等一些应激蛋白或有助于细菌适应抗生素;

    5.氨苄西林特异性差异表达基因均不位于可移动遗传元件附近。

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    内蒙古农业大学张文羿团队近期在mSystems发表研究,分析了植物乳杆菌P-8在对抗生素的适应中发生的变化,发现一些应激蛋白可能有助于细菌形成抗生素耐药表型,并表明相关基因通过可移动遗传元件传播给其它细菌的风险比较低。该研究为具有高耐药性的新型益生菌的生物安全性,提供了新的见解。

注:本研究的原文信息和链接出处,以及相关解读和评论文章。欢迎读者朋友们推荐!
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[IF:6.519]
Adaptation of Lactobacillus plantarum to Ampicillin Involves Mechanisms That Maintain Protein Homeostasis
植物乳杆菌对氨苄西林的适应涉及维持蛋白质稳态的机制
10.1128/mSystems.00853-19
01-28, Article
Abstract:收起
The widespread use of antibiotics has caused great concern in the biosafety of probiotics. In this study, we conducted a 12-month adaptive laboratory evolution (ALE) experiment to select for antibiotics-adapted Lactobacillus plantarum P-8, a dairy-originated probiotic bacterium. During the ALE process, the ampicillin MIC for the parental L. plantarum P-8 strain increased gradually and reached the maximum level of bacterial fitness. To elucidate the molecular mechanisms underlying the ampicillin-resistant phenotype, we comparatively analyzed the genomes and proteomes of the parental strain (L. plantarum P-8) and two adapted lines (L. plantarum 400g and L. plantarum 1600g). The adapted lines showed alterations in their carbon, amino acid, and cell surface-associated metabolic pathways. Then, gene disruption mutants were created to determine the role of six highly expressed genes in contributing to the enhanced ampicillin resistance. Inactivation of an ATP-dependent Clp protease/the ATP-binding subunit ClpL, a small heat shock protein, or a hypothetical protein resulted in partial but significant phenotypic reversion, confirming their necessary roles in the bacterial adaptation to ampicillin. Genomic analysis confirmed that none of the ampicillin-specific differential expressed genes were flanked by any mobile genetic elements; thus, even though long-term exposure to ampicillin upregulated their expression, there is low risk of spread of these genes and adapted drug resistance to other bacteria via horizontal gene transfer. Our study has provided evidence of the biosafety of probiotics even when used in the presence of antibiotics.
IMPORTANCE: Antibiotic resistance acquired by adaptation to certain antibiotics has led to growing public concerns. Here, a long-term evolution experiment was used together with proteomic analysis to identify genes/proteins responsible for the adaptive phenotype. This work has provided novel insights into the biosafety of new probiotics with high tolerance to antibiotics.

First Authors:
Chenxia Cao,Jicheng Wang
Correspondence Authors:
Wenyi Zhang
All Authors:
Chenxia Cao,Jicheng Wang,Yangshuo Liu,Lai-Yu Kwok,Heping Zhang,Wenyi Zhang


 



 
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