Induction of the reactive chlorine-responsive transcription factor RclR in Escherichia coli following ingestion by neutrophils.

Induction of the reactive chlorine-responsive transcription factor RclR in Escherichia coli following ingestion by neutrophils.
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中性粒细胞摄入后,大肠杆菌中活性氯反应转录因子 RclR 的诱导。

DOI:
10.1093/femspd/ftaa079
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发表时间:
2021
影响因子:
3.3
通讯作者:
Winterbourn,ChristineC
Winterbourn,ChristineC
中科院分区:
医学4区
文献类型:
--
作者:
Königstorfer,Andreas;Ashby,LouisaV;Bollar,GretchenE;Billiot,CaitlinE;Gray,MichaelJ;Jakob,Ursula;Hampton,MarkB;Winterbourn,ChristineC

文献摘要

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Neutrophils generate hypochlorous acid (HOCl) and related reactive chlorine species as part of their defence against invading microorganisms. In isolation, bacteria respond to reactive chlorine species by upregulating responses that provide defence against oxidative challenge. Key questions are whether these responses are induced when bacteria are phagocytosed by neutrophils, and whether this provides them with a survival advantage. We investigated RclR, a transcriptional activator of therclABCoperon inEscherichia colithat has been shown to be specifically activated by reactive chlorine species. We first measured induction by individual reactive chlorine species, and showed that HOCl itself activates the response, as do chloramines (products of HOCl reacting with amines) provided they are cell permeable. Strong RclR activation was seen inE. colifollowing phagocytosis by neutrophils, beginning within 5 min and persisting for 40 min. RclR activation was suppressed by inhibitors of NOX2 and myeloperoxidase, providing strong evidence that it was due to HOCl production in the phagosome. RclR activation demonstrates that HOCl, or a derived chloramine, enters phagocytosed bacteria in sufficient amount to induce this response. Although RclR was induced in wild-type bacteria following phagocytosis, we detected no greater sensitivity to neutrophil killing of mutants lacking genes in therclABCoperon.