Basu Thakur Poulami, Long Abagail R, Nelson Benjamin J, Kumar Ranjit, Rosenberg Alexander F, Gray Michael J
Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Auburn University, Auburn, Alabama, USA.
mSystems. 2019 Sep 3;4(5):e00453-19. doi: 10.1128/mSystems.00453-19.
Inflammatory diseases of the gut are associated with increased intestinal oxygen concentrations and high levels of inflammatory oxidants, including hydrogen peroxide (HO) and hypochlorous acid (HOCl), which are antimicrobial compounds produced by the innate immune system. This contributes to dysbiotic changes in the gut microbiome, including increased populations of proinflammatory enterobacteria ( and related species) and decreased levels of health-associated anaerobic and The pathways for HO and HOCl resistance in have been well studied, but little is known about how commensal and probiotic bacteria respond to inflammatory oxidants. In this work, we have characterized the transcriptomic response of the anti-inflammatory, gut-colonizing Gram-positive probiotic to both HO and HOCl. mounts distinct but overlapping responses to each of these stressors, and both gene expression and survival were strongly affected by the presence or absence of oxygen. Oxidative stress response in required several factors not found in enterobacteria, including the small heat shock protein Lo18, polyphosphate kinase 2, and RsiR, an -specific regulator of anti-inflammatory mechanisms. Reactive oxidants, including hydrogen peroxide and hypochlorous acid, are antimicrobial compounds produced by the immune system during inflammation. Little is known, however, about how many important types of bacteria present in the human microbiome respond to these oxidants, especially commensal and other health-associated species. We have now mapped the stress response to both HO and HOCl in the intestinal lactic acid bacterium .
肠道炎症性疾病与肠道氧浓度升高以及高水平的炎性氧化剂有关，这些氧化剂包括过氧化氢（H₂O₂）和次氯酸（HOCl），它们是先天免疫系统产生的抗菌化合物。这会导致肠道微生物群的生态失调变化，包括促炎性肠杆菌（及相关物种）数量增加以及与健康相关的厌氧菌水平降低。对大肠杆菌中H₂O₂和HOCl抗性的途径已有充分研究，但对于共生菌和益生菌如何应对炎性氧化剂却知之甚少。在这项研究中，我们已经对抗炎性、定殖于肠道的革兰氏阳性益生菌嗜酸乳杆菌对H₂O₂和HOCl的转录组反应进行了表征。嗜酸乳杆菌对每种应激源都呈现出不同但重叠的反应，并且基因表达和存活率都受到氧气存在与否的强烈影响。嗜酸乳杆菌中的氧化应激反应需要几种在肠杆菌中未发现的因子，包括小分子热休克蛋白Lo18、多磷酸激酶2以及RsiR（一种抗炎机制的嗜酸乳杆菌特异性调节因子）。活性氧化剂，包括过氧化氢和次氯酸，是免疫系统在炎症期间产生的抗菌化合物。然而，对于人类微生物群中存在的多种重要细菌类型如何应对这些氧化剂，尤其是共生菌和其他与健康相关的物种，我们知之甚少。我们现在已经绘制了肠道乳酸菌嗜酸乳杆菌对H₂O₂和HOCl的应激反应图谱。
