Thioredoxin reductase is essential for Thiol/Disulfide redox control and oxidative stress survival of the anaerobe Bacteroides fragilis
Thioredoxin reductase is essential for Thiol/Disulfide redox control and oxidative stress survival of the anaerobe Bacteroides fragilis
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DOI：
10.1128/jb.00714-07
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发表时间：
2007-11-01
影响因子：
3.2
通讯作者：
Smith, C. Jeffrey
中科院分区：
文献类型：
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作者：
Rocha, Edson R.;Tzianabos, Arthur O.;Smith, C. Jeffrey
这项研究的结果表明，厌氧条件下的脆弱类杆菌缺乏谷胱甘肽/谷氧还蛋白氧化还原系统，并具有大量推测的硫氧还蛋白(TRX)同源物。对基因组序列的分析显示，有6个Trx同源基因，但没有合成谷胱甘肽和谷氧还蛋白所需的基因。此外，硫氧还蛋白还原酶(TrxB)/Trx系统是该厌氧细菌中主要或唯一的硫醇/二硫化物细胞动态平衡的氧化还原系统。脆弱芽孢杆菌trxB基因的表达在联胺或过氧化氢处理或暴露在氧气中后被诱导。这种可诱导的trxB表达不依赖于OxyR。Northern杂交分析表明，trxB基因与LOLA以双顺反子形式共转录或以单顺反子形式存在，在相同条件下也有较高的诱导。LOLA是原核生物周质内脂蛋白特异的分子伴侣，在硫醇/二硫化物氧化还原系统中的作用尚不清楚。TrxB缺失突变体对联胺和氧气的影响比亲本菌株更敏感。此外，trxB突变体在没有添加还原剂的情况下不能在培养基中生长。此外，trxB突变体不能在小鼠模型中诱导腹内脓肿的形成，而亲本菌株则是。综上所述，这些数据有力地表明，TrxB/Trx是这种厌氧菌中主要的(如果不是唯一的)硫醇/二硫化物氧化还原系统，在腹膜腔感染模型中是生存和形成脓肿所必需的。
Results of this study showed that the anaerobic, opportunistic pathogen Bacteroides fragilis lacks the glutathione/glutaredoxin redox system and possesses an extensive number of putative thioredoxin (Trx) orthologs. Analysis of the genome sequence revealed six Trx orthologs and an absence of genes required for synthesis of glutathione and glutaredoxins. In addition, it was shown that the thioredoxin reductase (TrxB)/Trx system is the major or sole redox system for thiol/disulfide cellular homeostasis in this anaerobic bacterium. Expression of the B. fragilis trxB gene was induced following treatment with diamide or H2O2 or exposure to oxygen. This inducible trxB expression was OxyR independent. Northern blot hybridization analysis showed that the trxB mRNA was cotranscribed with lolA as a bicistronic transcript or was present as a monocistronic transcript that was also highly induced under the same conditions. The role of LolA, a prokaryotic periplasmic lipoprotein-specific molecular chaperone in the thiol/disulfide redox system, is unknown. A trxB deletion mutant was more sensitive to the effects of diamide and oxygen than the parent strain. In addition, the trxB mutant was unable to grow in culture media without addition of a reductant. Furthermore, the trxB mutant was not able to induce intraabdominal abscess formation in a mouse model, whereas the parent strain was. Taken together, these data strongly suggest that TrxB/Trx is the major, if not the sole, thiol/disulfide redox system in this anaerobe required for survival and abscess formation in a peritoneal cavity infection model.