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首页> 外文期刊>Frontiers in Cellular and Infection Microbiology >RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity
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RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity

机译：RegA在持久性的氧依赖性建立和异柠檬酸裂合酶活性（体内布鲁氏菌病致病性的关键决定因素）中起关键作用

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For aerobic human pathogens, adaptation to hypoxia is a critical factor for the establishment of persistent infections, as oxygen availability is low inside the host. The two-component system RegB/A of Brucella suis plays a central role in the control of respiratory systems adapted to oxygen deficiency, and in persistence in vivo. Using an original "in vitro model of persistence" consisting in gradual oxygen depletion, we compared transcriptomes and proteomes of wild-type and ?regA strains to identify the RegA-regulon potentially involved in the set-up of persistence. Consecutive to oxygen consumption resulting in growth arrest, 12 % of the genes in B. suis were potentially controlled directly or indirectly by RegA, among which numerous transcriptional regulators were up-regulated. In contrast, genes or proteins involved in envelope biogenesis and in cellular division were repressed, suggesting a possible role for RegA in the set-up of a non-proliferative persistence state. Importantly, the greatest number of the RegA-repressed genes and proteins, including aceA encoding the functional IsoCitrate Lyase (ICL), were involved in energy production. A potential consequence of this RegA impact may be the slowing-down of the central metabolism as B. suis progressively enters into persistence. Moreover, ICL is an essential determinant of pathogenesis and long-term interactions with the host, as demonstrated by the strict dependence of B. suis on ICL activity for multiplication and persistence during in vivo infection. RegA regulates gene or protein expression of all functional groups, which is why RegA is a key regulator of B. suis in adaptation to oxygen depletion. This function may contribute to the constraint of bacterial growth, typical of chronic infection. Oxygen-dependent activation of two-component systems that control persistence regulons, shared by several aerobic human pathogens, has not been studied in Brucella sp. before. This work therefore contributes significantly to the unravelling of persistence mechanisms in this important zoonotic pathogen.
机译：对于有氧人类病原体，适应性低氧是建立持续感染的关键因素，因为宿主体内的氧气利用率较低。猪布鲁氏菌的两组分系统RegB / A在控制呼吸系统以适应缺氧和体内持久性方面起着中心作用。使用最初的“体外持久性模型”（包括逐步耗氧），我们比较了野生型和？regA菌株的转录组和蛋白质组，以确定可能参与持久性建立的RegA-regulon。与耗氧量导致生长停滞相伴，Reg.A可能直接或间接控制了猪双歧杆菌中12％的基因，其中许多转录调节因子均被上调。相比之下，参与包膜生物发生和细胞分裂的基因或蛋白质被抑制，表明RegA在建立非增殖性持久状态中可能发挥作用。重要的是，最大数量的RegA抑制基因和蛋白质，包括编码功能性异柠檬酸裂解酶（ICL）的aceA，都参与了能量产生。 RegA影响的潜在结果可能是随着猪芽孢杆菌逐渐进入持久性而降低中央代谢。此外，如在体内感染期间猪双歧杆菌对ICL活性的严格依赖性所证明的，ICL是发病机理和与宿主的长期相互作用的重要决定因素。 RegA调节所有功能基团的基因或蛋白质表达，这就是RegA是猪双歧杆菌对氧耗竭适应性的关键调节剂的原因。该功能可能有助于限制细菌的生长，这是典型的慢性感染。在布鲁氏菌属菌种中尚未研究控制由持久性调节因子控制的两组分系统的氧依赖性活化，该持久性调节因子由几种有氧人类病原体共享。之前。因此，这项工作大大有助于揭示这种重要的人畜共患病原体中的持久性机制。

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