The Campylobacter jejuni MarR-like transcriptional regulators RrpA and RrpB both influence bacterial responses to oxidative and aerobic stresses.
The Campylobacter jejuni MarR-like transcriptional regulators RrpA and RrpB both influence bacterial responses to oxidative and aerobic stresses.
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DOI：
10.3389/fmicb.2015.00724
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发表时间：
2015
影响因子：
5.2
通讯作者：
Dorrell N
中科院分区：
文献类型：
--
作者：
Gundogdu O;da Silva DT;Mohammad B;Elmi A;Mills DC;Wren BW;Dorrell N
人类肠道病原体空肠弯曲杆菌对氧化应激的反应能力是细菌在体内感染期间和环境中生存的核心。对空肠弯曲菌NCTC11168基因组的重新注释揭示了两个Marr型转录调控因子Cj1546和Cj1556的存在，最初被注释为假设蛋白质，我们分别命名为RrpA和RrpB(过氧化反应调节因子)。以前，我们证明了RrpB在氧化和有氧(O2)应激中的作用，并且RrpB是一种具有自动调节活性的DNA结合蛋白，典型的Marr型转录调节因子。在这项研究中，我们发现RrpA也是一种DNA结合蛋白，并且菌株11168H中的rrpA突变体对过氧化氢氧化应激表现出更高的敏感性。RrpA或rrpB的突变降低了过氧化氢酶(KATA)的表达。然而，rrpAB双突变体对过氧化氢氧化胁迫表现出更高的抗性，其KATA表达水平与野生型菌株相似。RrpA或rrpB的突变也导致KATA表达水平下降，但在rrpAB双突变体中没有观察到这种下降。RrpA和rrpB突变体在对异丙苯过氧化氢或甲双酮氧化应激的敏感性方面都没有表现出明显的差异，但在Galeria mellonella感染模型中，这两个突变体都表现出在有氧(O2)胁迫下生存能力降低、生物膜形成增加和毒力降低。在G-mellonella感染模型中，rrpAB双重突变体显示出野生型生物膜形成和野生型毒力水平。总之，这些数据表明RrpA和RrpB在空肠弯曲菌过氧化氢氧化和好氧(O2)应激反应中都发挥了作用，从而提高了细菌在体内和环境中的生存。
The ability of the human intestinal pathogen Campylobacter jejuni to respond to oxidative stress is central to bacterial survival both in vivo during infection and in the environment. Re-annotation of the C. jejuni NCTC11168 genome revealed the presence of two MarR-type transcriptional regulators Cj1546 and Cj1556, originally annotated as hypothetical proteins, which we have designated RrpA and RrpB (regulator of response to peroxide) respectively. Previously we demonstrated a role for RrpB in both oxidative and aerobic (O2) stress and that RrpB was a DNA binding protein with auto-regulatory activity, typical of MarR-type transcriptional regulators. In this study, we show that RrpA is also a DNA binding protein and that a rrpA mutant in strain 11168H exhibits increased sensitivity to hydrogen peroxide oxidative stress. Mutation of either rrpA or rrpB reduces catalase (KatA) expression. However, a rrpAB double mutant exhibits higher levels of resistance to hydrogen peroxide oxidative stress, with levels of KatA expression similar to the wild-type strain. Mutation of either rrpA or rrpB also results in a reduction in the level of katA expression, but this reduction was not observed in the rrpAB double mutant. Neither the rrpA nor rrpB mutant exhibits any significant difference in sensitivity to either cumene hydroperoxide or menadione oxidative stresses, but both mutants exhibit a reduced ability to survive aerobic (O2) stress, enhanced biofilm formation and reduced virulence in the Galleria mellonella infection model. The rrpAB double mutant exhibits wild-type levels of biofilm formation and wild-type levels of virulence in the G mellonella infection model. Together these data indicate a role for both RrpA and RrpB in the C. jejuni peroxide oxidative and aerobic (O2) stress responses, enhancing bacterial survival in vivo and in the environment.