Bower Jean M, Mulvey Matthew A
Pathology Department, Division of Cell Biology and Immunology, University of Utah, 15 North Medical Dr. East, Salt Lake City, UT 84112-0565, USA.
J Bacteriol. 2006 Feb;188(3):928-33. doi: 10.1128/JB.188.3.928-933.2006.
During the course of a urinary tract infection, substantial levels of nitric oxide and reactive nitrogen intermediates are generated. We have found that many uropathogenic strains of Escherichia coli display far greater resistance to nitrosative stress than the K-12 reference strain MG1655. By selecting and screening for uropathogenic E. coli transposon mutants that are unable to grow in the presence of acidified nitrite, the cadC gene product was identified as a key facilitator of nitrosative stress resistance. Mutation of cadC, or its transcriptional targets cadA and cadB, results in loss of significant production of the polyamine cadaverine and increased sensitivity to acidified nitrite. Exogenous addition of cadaverine or other polyamines rescues growth of cad mutants under nitrosative stress. In wild-type cells, the concentration of cadaverine produced per cell is substantially increased by exposure to acidified nitrite. The mechanism behind polyamine-mediated rescue from nitrosative stress is unclear, but it is not attributable solely to chemical quenching of reactive nitrogen species or reduction in mutation frequency.
在尿路感染过程中，会产生大量的一氧化氮和活性氮中间体。我们发现，许多致病性大肠杆菌菌株对亚硝化应激的抗性远高于K-12参考菌株MG1655。通过选择和筛选在酸化亚硝酸盐存在下无法生长的致病性大肠杆菌转座子突变体，cadC基因产物被鉴定为亚硝化应激抗性的关键促进因子。cadC或其转录靶点cadA和cadB的突变会导致多胺尸胺的大量产生丧失，并增加对酸化亚硝酸盐的敏感性。在亚硝化应激下，外源添加尸胺或其他多胺可挽救cad突变体的生长。在野生型细胞中，暴露于酸化亚硝酸盐会使每个细胞产生的尸胺浓度大幅增加。多胺介导的亚硝化应激解救背后的机制尚不清楚，但这不仅仅归因于活性氮物种的化学淬灭或突变频率的降低。
