Cereija Tatiana Barros, Alarico Susana, Lourenço Eva C, Manso José António, Ventura M Rita, Empadinhas Nuno, Macedo-Ribeiro Sandra, Pereira Pedro José Barbosa
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
IUCrJ. 2019 May 8;6(Pt 4):572-585. doi: 10.1107/S2052252519005372. eCollection 2019 Jul 1.
Bacteria are challenged to adapt to environmental variations in order to survive. Under nutritional stress, several bacteria are able to slow down their metabolism into a nonreplicating state and wait for favourable conditions. It is almost universal that bacteria accumulate carbon stores to survive during this nonreplicating state and to fuel rapid proliferation when the growth-limiting stress disappears. Mycobacteria are exceedingly successful in their ability to become dormant under harsh circumstances and to be able to resume growth when conditions are favourable. Rapidly growing mycobacteria accumulate glucosylglycerate under nitrogen-limiting conditions and quickly mobilize it when nitrogen availability is restored. The depletion of intracellular glucosyl-glycerate levels in (basonym ) was associated with the up-regulation of the gene coding for glucosylglycerate hydrolase (GgH), an enzyme that is able to hydrolyse glucosylglycerate to glycerate and glucose, a source of readily available energy. Highly conserved among unrelated phyla, GgH is likely to be involved in bacterial reactivation following nitrogen starvation, which in addition to other factors driving mycobacterial recovery may also provide an opportunity for therapeutic intervention, especially in the serious infections caused by some emerging opportunistic pathogens of this group, such as (basonym ). Using a combination of biochemical methods and hybrid structural approaches, the oligomeric organization of GgH was determined and molecular determinants of its substrate binding and specificity were unveiled.
细菌为了生存需要适应环境变化。在营养应激下，一些细菌能够将新陈代谢减缓至非复制状态，等待有利条件。几乎所有细菌都会积累碳储存，以便在这种非复制状态下生存，并在生长限制应激消失时为快速增殖提供能量。分枝杆菌在恶劣环境下进入休眠状态并在条件有利时恢复生长的能力非常突出。快速生长的分枝杆菌在氮限制条件下积累葡糖甘油酸，并在氮供应恢复时迅速动员它。在（旧称）中，细胞内葡糖甘油酸水平的耗尽与编码葡糖甘油酸水解酶（GgH）的基因上调有关，该酶能够将葡糖甘油酸水解为甘油酸和葡萄糖，这是一种易于获取的能量来源。GgH在不相关的菌门中高度保守，可能参与氮饥饿后的细菌重新激活，这除了其他驱动分枝杆菌恢复的因素外，还可能为治疗干预提供机会，特别是在由该类一些新兴机会性病原体引起的严重感染中，如（旧称）。通过结合生化方法和混合结构方法，确定了GgH的寡聚结构，并揭示了其底物结合和特异性的分子决定因素。
