Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion.

Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion.
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DOI:
10.1038/s41467-018-06701-4
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发表时间:
2018-10-10
影响因子:
16.6
通讯作者:
Roe AJ
Roe AJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Connolly JPR;Slater SL;O'Boyle N;Goldstone RJ;Crepin VF;Ruano-Gallego D;Herzyk P;Smith DGE;Douce GR;Frankel G;Roe AJ

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Niche-adaptation of a bacterial pathogen hinges on the ability to recognize the complexity of signals from the environment and integrate that information with the regulation of genes critical for infection. Here we report the transcriptome of the attaching and effacing pathogen Citrobacter rodentium during infection of its natural murine host. Pathogen gene expression in vivo was heavily biased towards the virulence factor repertoire and was found to be co-ordinated uniquely in response to the host. Concordantly, we identified the host-specific induction of a metabolic pathway that overlapped with the regulation of virulence. The essential type 3 secretion system and an associated suite of distinct effectors were found to be modulated co-ordinately through a unique mechanism involving metabolism of microbiota-derived 1,2-propanediol, which dictated the ability to colonize the host effectively. This study provides novel insights into how host-specific metabolic adaptation acts as a cue to fine-tune virulence. Infection of mice with Citrobacter rodentium is a common model of infection with attaching-and-effacing pathogens. Here, Connolly et al. analyse the transcriptome of C. rodentium during mouse infection, showing host-induced coordinated upregulation of virulence factors and 1,2-propanediol metabolism.
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