Brucella abortus Rough-Type Mutant Induces Ferroptosis and More Oxidative Stress in Infected Macrophages.
Brucella abortus Rough-Type Mutant Induces Ferroptosis and More Oxidative Stress in Infected Macrophages.
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DOI：
10.3390/pathogens12101189
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发表时间：
2023-09-23
期刊：
影响因子：
--
通讯作者：
Yu S
中科院分区：
文献类型：
--
作者：
Hu H;Zhang G;Tian M;Guan X;Yin Y;Ding C;Yu S
布鲁氏菌是一种细胞内寄生细菌，它使用多种策略来逃避宿主的防御机制。然而，布鲁氏菌如何操纵宿主诱导的氧化应激以及相关的生物学过程仍然知之甚少。本研究通过对感染布鲁氏菌S2308及其粗略突变株RB14的巨噬细胞进行比较转录组分析，寻找可能与布鲁氏菌致病机制相关的差异表达基因。我们的结果表明，在感染流产杆菌S2308和突变株RB14的巨噬细胞中，在感染后4、8、24和48h，大量的宿主促氧化和抗氧化应激基因有差异表达。有趣的是，我们发现了几个铁下垂相关基因在流产杆菌RB14感染过程中的差异表达。此外，我们发现粗略突变体RB14诱导的巨噬细胞死亡与宿主谷胱甘肽和谷胱甘肽过氧化物酶4水平的降低以及游离铁、脂质过氧化和ROS的增加有关，所有这些都是铁下垂的重要标志。在感染RB14期间发生的铁下垂可以通过抑制铁蛋白-1的治疗而减少。然而，流产杆菌S2308感染并没有引起这些铁性下垂的症状。综上所述，我们的结果表明铁性下垂与粗大的流产杆菌感染有关。研究布鲁氏菌如何调控宿主体内的氧化应激和铁下垂，将有助于阐明流产布鲁氏菌的致病性。
Brucella is an intracellular parasitic bacterium that uses multiple strategies to evade the host’s defense mechanisms. However, how Brucella manipulates the host-induced oxidative stress and relevant biological processes are still poorly understood. In this study, a comparative transcriptome assay of macrophages infected with Brucella abortus S2308 and its rough mutant RB14 was performed to investigate the differentially expressed genes which might be associated with the pathogenic mechanism of Brucella. Our results showed that numerous host pro-oxidative and antioxidative stress genes were differentially expressed in macrophages infected with B. abortus S2308 and mutant RB14 at 4, 8, 24, and 48 h post-infection. Interestingly, we found that several ferroptosis-associated genes were differentially expressed during B. abortus RB14 infection. Moreover, we found that the rough mutant RB14-induced macrophage death was associated with reduced levels of host glutathione and glutathione peroxidase 4, together with increased free iron, lipid peroxidation, and ROS, all of which are important hallmarks of ferroptosis. The ferroptosis occurring during infection with RB14 was reduced by treatment with the inhibitor ferrostatin-1. However, B. abortus S2308 infection did not induce these hallmarks of ferroptosis. Taken together, our results demonstrate that ferroptosis is involved in rough B. abortus infection. Investigating how Brucella manipulates oxidative stress and ferroptosis in its host will be helpful to clarify the pathogenicity of B. abortus.
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影响因子：
4.4
作者：
Hu, Hai;Tian, Mingxing;Yu, Shengqing
通讯作者：
Yu, Shengqing
ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
5.7
作者：
Pei J;Kahl-McDonagh M;Ficht TA
通讯作者：
Ficht TA
影响因子：
32.4
作者：
Bronner DN;Abuaita BH;Chen X;Fitzgerald KA;Nuñez G;He Y;Yin XM;O'Riordan MX
通讯作者：
O'Riordan MX