The Roles of the Two-Component System, MtrAB, in Response to Diverse Cell Envelope Stresses in Dietzia sp. DQ12-45-1b.
The Roles of the Two-Component System, MtrAB, in Response to Diverse Cell Envelope Stresses in Dietzia sp. DQ12-45-1b.
复制标题
DOI：
10.1128/aem.01337-22
复制
发表时间：
2022-10-26
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
作者：
双组分系统（TCS）作为一种常见的调节系统，允许细菌检测和响应多种环境刺激，包括细胞包膜应激。放线菌的MtrAB TCS对于细胞壁稳态、细胞增殖、细菌保护和抗生素抗性至关重要，因此发现其在该门中高度保守。然而，MtrAB TCS如何精确地调节细胞内稳态以响应环境应激仍不清楚。在这里，我们表明，MtrAB TCS在耐受不同类型的细胞包膜应力，包括环境应力（即，氧化应激、溶菌酶、SDS、渗透压和碱性pH应激）和靶向细菌的抗生素（即，异烟肼、乙胺丁醇、糖肽和β-内酰胺类抗生素）。与野生型菌株相比，mtrAB突变菌株表现出较慢的生长，并且当暴露于各种环境应力时，其特征在于异常的细胞形状。此外，mtrAB的缺失导致对异烟肼、乙胺丁醇和β-内酰胺类抗生素的耐药性降低。此外，靶下切割和标签化测序（CUT&Tag-seq）和电泳迁移率变动测定（EMSA）揭示了MtrA结合参与肽聚糖生物合成（ldtB、ldtA、murJ）、水解（GJR88_03483、GJR88_4713）和细胞分裂（ftsE）的基因的启动子。总之，我们的研究结果表明，MtrAB TCS对于迪茨氏菌DQ 12 -45-1b在各种细胞包膜应激下的存活至关重要，主要是通过控制多个下游细胞途径。我们的工作表明，TCS作为全球传感器和调节器，在维持细胞内稳态，如在各种环境压力的事件。本研究将有助于了解细菌对极端环境的适应机制。多层细胞被膜是细菌抵御各种极端环境的第一道防线。细菌利用大量的传感和调节系统在多种应激条件下维持细胞被膜稳态。双组分系统（TCS）是环境适应的主要感知和响应装置。在放线菌中高度保守的MtrAB TCS对于细胞壁稳态、细胞增殖、细菌保护和抗生素抗性至关重要。然而，MtrAB如何与影响细胞包络变化的信号有关，尚未完全了解。在此，我们发现在放线杆菌Dietzia sp. DQ 12 -45-1b中，一种名为MtrAB的TCS对于确保正常细胞生长以及维持适当的细胞形态以响应各种细胞被膜应力是关键的，即，通过调节细胞凋亡相关基因的表达。我们的研究结果将大大推进我们对在持续环境冲击下维持细胞完整性的适应机制的理解。
Two-component systems (TCSs) act as common regulatory systems allowing bacteria to detect and respond to multiple environmental stimuli, including cell envelope stress. The MtrAB TCS of Actinobacteria is critical for cell wall homeostasis, cell proliferation, osmoprotection, and antibiotic resistance, and thus is found to be highly conserved across this phylum. However, how precisely the MtrAB TCS regulates cellular homeostasis in response to environmental stress remains unclear. Here, we show that the MtrAB TCS plays an important role in the tolerance to different types of cell envelope stresses, including environmental stresses (i.e., oxidative stress, lysozyme, SDS, osmotic pressure, and alkaline pH stresses) and envelope-targeting antibiotics (i.e., isoniazid, ethambutol, glycopeptide, and β-lactam antibiotics) in Dietzia sp. DQ12-45-1b. An mtrAB mutant strain exhibited slower growth compared to the wild-type strain and was characterized by abnormal cell shapes when exposed to various environmental stresses. Moreover, deletion of mtrAB resulted in decreased resistance to isoniazid, ethambutol, and β-lactam antibiotics. Further, Cleavage under targets and tagmentation sequencing (CUT&Tag-seq) and electrophoretic mobility shift assays (EMSAs) revealed that MtrA binds the promoters of genes involved in peptidoglycan biosynthesis (ldtB, ldtA, murJ), hydrolysis (GJR88_03483, GJR88_4713), and cell division (ftsE). Together, our findings demonstrated that the MtrAB TCS is essential for the survival of Dietzia sp. DQ12-45-1b under various cell envelope stresses, primarily by controlling multiple downstream cellular pathways. Our work suggests that TCSs act as global sensors and regulators in maintaining cellular homeostasis, such as during episodes of various environmental stresses. The present study should shed light on the understanding of mechanisms for bacterial adaptivity to extreme environments. IMPORTANCE The multilayered cell envelope is the first line of bacterial defense against various extreme environments. Bacteria utilize a large number of sensing and regulatory systems to maintain cell envelope homeostasis under multiple stress conditions. The two-component system (TCS) is the main sensing and responding apparatus for environmental adaptation. The MtrAB TCS highly conserved in Actinobacteria is critical for cell wall homeostasis, cell proliferation, osmoprotection, and antibiotic resistance. However, how MtrAB works with regard to signals impacting changes to the cell envelope is not fully understood. Here, we found that in the Actinobacterium Dietzia sp. DQ12-45-1b, a TCS named MtrAB is pivotal for ensuring normal cell growth as well as maintaining proper cell morphology in response to various cell envelope stresses, namely, by regulating the expression of cell envelope-related genes. Our findings should greatly advance our understanding of the adaptive mechanisms responsible for maintaining cell integrity in times of sustained environmental shocks.
登录
查看更多内容
影响因子：
4.8
作者：
Banerjee, Srijon;Lata, Suruchi;Kundu, Manikuntala
通讯作者：
Kundu, Manikuntala
影响因子：
3.2
作者：
Brocker, Melanie;Mack, Christina;Bott, Michael
通讯作者：
Bott, Michael
影响因子：
3.6
作者：
Dubrac, Sarah;Bisicchia, Paola;Msadek, Tarek
通讯作者：
Msadek, Tarek
影响因子：
11.8
作者：
Bemer-Melchior, P;Haloun, A;Drugeon, HB
通讯作者：
Drugeon, HB
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS