Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP
Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP
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镁将饥饿介导的抗生素持久性与 ATP 联系起来
DOI：
10.1128/msphere.00862-19
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发表时间：
2020-01
期刊：
影响因子：
4.8
通讯作者：
Wenhong Zhang
中科院分区：
文献类型：
--
作者：
Tao Xu;Xuyang Wang;Lu Meng;Mengqi Zhu;Jing Wu;Yuanyuan Xu;Ying Zhang;Wenhong Zhang
不同的基因参与细菌的持续体的形成，无论是否存在持续体基因。尽管最近发现了ATP和膜电位在持久形成中的作用，但触发ATP或膜电位变化的关键因素仍然难以捉摸。我们的工作表明，镁离子而不是其他离子或营养成分是持续存在的关键元素，它通过诱导细胞质ATP的减少，进而诱导持久形成。此外，我们还观察到金黄色葡萄球菌在不同生长阶段对镁离子转运基因的严格调控。这些发现表明，尽管镁是一种关键的营养物质，但在生长过程中，镁也是形成持续体的关键信号。摘要随着细菌培养从对数阶段发展到固定阶段，细菌持久菌随着时间的推移而出现和数量增加。然而，这一不可避免趋势的潜在基础尚不清楚。在这项研究中，我们研究了营养物质在饥饿介导的金黄色葡萄球菌持久形成中的作用。通过对营养成分的筛选，我们发现添加镁离子可以逆转饥饿诱导的对数相培养的持久形成，但不能通过添加氨基酸、核苷酸或其他盐来逆转。此外，剥夺胞外镁离子会降低细胞质中的三磷酸腺苷，从而在不影响胞内镁离子或膜电位的情况下诱导持续性。最后，我们发现，镁离子降低了固定细胞标记基因cap5A和arca的表达。这些发现表明，镁离子水平与代表新陈代谢状态并在生长过程中调节抗生素持久性的ATP之间存在联系。重要性各种基因已被确定参与细菌持续体的形成，无论是否存在持续体基因。尽管最近发现了ATP和膜电位在持久形成中的作用，但触发ATP或膜电位变化的关键因素仍然难以捉摸。我们的工作表明，镁离子而不是其他离子或营养成分是持续存在的关键元素，它通过诱导细胞质ATP的减少，进而诱导持久形成。此外，我们还观察到金黄色葡萄球菌在不同生长阶段对镁离子转运基因的严格调控。这些发现表明，尽管镁是一种关键的营养物质，但在生长过程中，镁也是形成持续体的关键信号。
Various genes have been identified to be involved in bacterial persister formation regardless of the presence or absence of persister genes. Despite recent discoveries of the roles of ATP and membrane potential in persister formation, the key element that triggers change of ATP or membrane potential remains elusive. Our work demonstrates that Mg2+ instead of other ions or nutrient components is the key element for persistence by inducing a decrease of cytoplasmic ATP, which subsequently induces persister formation. In addition, we observed tight regulation of genes for Mg2+ transport in different growth phases in S. aureus. These findings indicate that despite being a key nutrient, Mg2+ also served as a key signal in persister formation during growth. ABSTRACT Bacterial persisters emerge and increase in numbers over time as a bacterial culture grows from log phase to stationary phase. However, the underlying basis of the inevitable tendency is unclear. In this study, we investigated the role of nutrients in starvation-mediated persister formation of Staphylococcus aureus. By screening of nutrient components, we found that starvation-induced persister formation of log-phase cultures could be reversed by addition of magnesium (Mg2+) but not amino acids, nucleotides, or other salts. Further, deprivation of extracellular Mg2+ reduced cytoplasmic ATP, inducing persistence without affecting cytoplasmic Mg2+ or membrane potential. Finally, we showed that Mg2+ reduced expression of stationary cell marker genes, cap5A and arcA. These findings indicate a connection between Mg2+ levels and ATP, which represents metabolic status and mediates antibiotic persistence during growth. IMPORTANCE Various genes have been identified to be involved in bacterial persister formation regardless of the presence or absence of persister genes. Despite recent discoveries of the roles of ATP and membrane potential in persister formation, the key element that triggers change of ATP or membrane potential remains elusive. Our work demonstrates that Mg2+ instead of other ions or nutrient components is the key element for persistence by inducing a decrease of cytoplasmic ATP, which subsequently induces persister formation. In addition, we observed tight regulation of genes for Mg2+ transport in different growth phases in S. aureus. These findings indicate that despite being a key nutrient, Mg2+ also served as a key signal in persister formation during growth.
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影响因子：
5.6
作者：
Pontes MH;Sevostyanova A;Groisman EA
通讯作者：
Groisman EA
DOI：
10.1186/1757-1626-2-199
发表时间：
2009-11-18
期刊：
Cases journal
影响因子：
--
作者：
Corsello S;Fulgenzi A;Vietti D;Ferrero ME
通讯作者：
Ferrero ME
影响因子：
6.4
作者：
Monk IR;Shah IM;Xu M;Tan MW;Foster TJ
通讯作者：
Foster TJ
影响因子：
6.4
作者：
Shan Y;Brown Gandt A;Rowe SE;Deisinger JP;Conlon BP;Lewis K
通讯作者：
Lewis K
影响因子：
4.5
作者：
Bernier SP;Lebeaux D;DeFrancesco AS;Valomon A;Soubigou G;Coppée JY;Ghigo JM;Beloin C
通讯作者：
Beloin C