MOB rules: Antibiotic Exposure Reprograms Metabolism to Mobilize Bacillus subtilis in Competitive Interactions.
MOB rules: Antibiotic Exposure Reprograms Metabolism to Mobilize Bacillus subtilis in Competitive Interactions.
复制标题
MOB 规则：抗生素暴露会重新编程代谢，以在竞争性相互作用中动员枯草芽孢杆菌。
DOI：
10.1101/2024.03.20.585991
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Straight,PaulD
中科院分区：
文献类型：
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作者：
Liu,Yongjin;LaBonte,Sandra;Brake,Courtney;LaFayette,Carol;Rosebrock,AdamP;Caudy,AmyA;Straight,PaulD
抗生素对暴露的细菌具有剂量依赖性作用。抗生素的药用依赖于它们在足够浓度下的生长抑制活性。在亚抑菌浓度下，不同抗生素和细菌的暴露效应差异很大。枯草芽孢杆菌通过动员细胞群体（MOB动员芽孢杆菌）在表面上扩散来响应抑菌翻译抑制剂。怎么样B。枯草芽孢杆菌调节植物诱导的动员是未知的。在这项研究中，我们使用氯霉素，以确定调节功能，B。枯草芽孢杆菌需要在亚抑制暴露后协调细胞动员。我们测量了基因表达和代谢的变化，并将结果映射到指导移动的反应的调节蛋白网络。我们的数据显示，几个转录调节协调控制代谢的重编程，以支持动员。该网络调节糖酵解、核苷酸代谢和氨基酸代谢的变化，这些变化是动员群体的特征。在数百个表达变化的基因中，我们确定了两个，pdhA和pucA，其表达变化的幅度和相关代谢物的丰度，揭示了动员人群的标志性代谢特征。使用pdhA和pucA表达的报告者，我们可视化了动员群体的不同区域中代谢的主要分支的分离。我们的研究结果揭示了一个调节响应氯霉素暴露，使人口的细菌在不同的代谢状态，安装一个协调的移动的响应。
Antibiotics have dose-dependent effects on exposed bacteria. The medicinal use of antibiotics relies on their growth-inhibitory activities at sufficient concentrations. At subinhibitory concentrations, exposure effects vary widely among different antibiotics and bacteria. Bacillus subtilis responds to bacteriostatic translation inhibitors by mobilizing a population of cells (MOB-Mobilized Bacillus) to spread across a surface. How B. subtilis regulates the antibiotic-induced mobilization is not known. In this study, we used chloramphenicol to identify regulatory functions that B. subtilis requires to coordinate cell mobilization following subinhibitory exposure. We measured changes in gene expression and metabolism and mapped the results to a network of regulatory proteins that direct the mobile response. Our data reveal that several transcriptional regulators coordinately control the reprogramming of metabolism to support mobilization. The network regulates changes in glycolysis, nucleotide metabolism, and amino acid metabolism that are signature features of the mobilized population. Among the hundreds of genes with changing expression, we identified two, pdhA and pucA, where the magnitudes of their changes in expression, and in the abundance of associated metabolites, reveal hallmark metabolic features of the mobilized population. Using reporters of pdhA and pucA expression, we visualized the separation of major branches of metabolism in different regions of the mobilized population. Our results reveal a regulated response to chloramphenicol exposure that enables a population of bacteria in different metabolic states to mount a coordinated mobile response.