Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland.
J Virol. 2011 Nov;85(22):12032-42. doi: 10.1128/JVI.00275-11. Epub 2011 Aug 31.
In this study, whole-genome microarrays were used to gain insights into the global molecular response of Lactococcus lactis subsp. lactis IL1403 at an early stage of infection with the lytic phage c2. The bacterium differentially regulated the expression of 61 genes belonging to 14 functional categories, including cell envelope processes (12 genes), regulatory functions (11 genes), and carbohydrate metabolism (7 genes). The nature of these genes suggests a complex response involving four main mechanisms: (i) induction of membrane stress proteins, (ii) d-alanylation of cell wall lipoteichoic acids (LTAs), (iii) maintenance of the proton motive force (PMF), and (iv) energy conservation. The phage presence is sensed as a membrane stress in L. lactis subsp. lactis IL1403, which activated a cell wall-targeted response probably orchestrated by the concerted action of membrane phage shock protein C-like homologues, the global regulator SpxB, and the two-component system CesSR. The bacterium upregulated genes (ddl and dltABCD) responsible for incorporation of d-alanine esters into LTAs, an event associated with increased resistance to phage attack in Gram-positive bacteria. The expression of genes (yshC, citE, citF) affecting both PMF components was also regulated to restore the physiological PMF, which was disrupted following phage infection. While mobilizing the response to the phage-mediated stress, the bacterium activated an energy-saving program by repressing growth-related functions and switching to anaerobic respiration, probably to sustain the PMF and the overall cell response to phage. To our knowledge, this represents the first detailed description in L. lactis of the molecular mechanisms involved in the host response to the membrane perturbations mediated by phage infection.
在这项研究中，使用全基因组微阵列深入了解了乳酸乳球菌亚种 lactis IL1403 在早期感染溶菌噬菌体 c2 时的全局分子反应。细菌差异调节了属于 14 个功能类别的 61 个基因的表达，包括细胞包膜过程（12 个基因）、调节功能（11 个基因）和碳水化合物代谢（7 个基因）。这些基因的性质表明涉及四个主要机制的复杂反应：（i）诱导膜应激蛋白，（ii）细胞壁脂磷壁酸（LTAs）的 d-丙氨酸化，（iii）质子动力势（PMF）的维持，和（iv）能量守恒。噬菌体的存在被感知为乳酸乳球菌亚种 lactis IL1403 中的膜应激，这激活了细胞壁靶向反应，可能由膜噬菌体休克蛋白 C 样同源物、全局调节剂 SpxB 和双组分系统 CesSR 的协同作用协调。细菌上调了负责将 d-丙氨酸酯掺入 LTAs 的基因（ddl 和 dltABCD），这与革兰氏阳性菌对噬菌体攻击的抗性增加有关。影响 PMF 两个组成部分的基因（yshC、citE、citF）的表达也受到调节，以恢复生理 PMF，该 PMF在噬菌体感染后被破坏。在动员对噬菌体介导的应激的反应的同时，细菌通过抑制与生长相关的功能并切换到厌氧呼吸来激活节能程序，可能是为了维持 PMF 和细胞对噬菌体的整体反应。据我们所知，这是在乳酸乳球菌中首次详细描述宿主对噬菌体感染介导的膜扰动的分子机制。
