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ABSTRACT: Whole-genome sequencing of hypervirulent and carbapenem-resistant Klebsiella pneumonia

PROVIDER: PRJNA1043403 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26895500_1.fastq.gz	Fastqsanger.gz
	SRR26895501_1.fastq.gz	Fastqsanger.gz
	SRR26895502_1.fastq.gz	Fastqsanger.gz
	SRR26895503_1.fastq.gz	Fastqsanger.gz
	SRR26895504_1.fastq.gz	Fastqsanger.gz

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RNA interactome profiling in hypervirulent Klebsiella pneumoniae reveals small RNA ArcZ as an inhibitor of mucoviscosity and virulence

Project description:Hypervirulent Klebsiella pneumoniae (HvKP) is an emerging human pathogen causing invasive infection in immune-competent hosts. The hypervirulence is strongly linked to the overproduction of hypermucovisous capsule, but the underlining regulatory mechanism of hypermucoviscosity (HMV) has been elusive, especially at the post-transcriptional level mediated by small RNAs (sRNAs). Using a recently developed RNA interactome profiling approach, we have investigated the Hfq-associated sRNA regulatory network and established the first in vivo RNA-RNA interactome in HvKP. Our data reveal numerous interactions between sRNAs and HMV-related mRNAs, and identify a plethora of sRNA that inhibit or promote HMV. One of the strongest repressors of HMV was ArcZ, a conserved sRNA in the Enterobacteriaceae family. We found that ArcZ is activated by the master regulator of catabolite repression Crp, and down-regulates the expression of mlaA encoding an outer-membrane lipoprotein, leading to decreased HMV and virulence attenuation in mice. ArcZ significantly reduced HMV in several carbapenem-resistant and hypervirulent clinical isolates with diverse genetic background, suggesting it is an antisense RNA inhibitor of HMV with therapeutic potential. In summary, our work provides a comprehensive map of the RNA-RNA interaction network of HvKP and identifies ArcZ as a conserved repressor of HMV, providing novel insights into the mechanisms of posttranscriptional regulations of virulence.

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