Abstract
Cronobacter sakazakii is an important neonatal pathogen frequently associated with powdered infant formula. However, the mechanisms by which C. sakazakii adapts to the host environment and establishes systemic dissemination remain poorly understood. Here, we reveal a signal transduction pathway centered on a novel sRNA, CsrN, which facilitates C. sakazakii in utilizing nitrate respiration in response to oxygen-limited environments within the host, thereby enhancing its virulence in vivo. C. sakazakii infection triggers an inflammatory response, leading to the accumulation of host-derived nitrate, a key alternative electron acceptor. The expression of CsrN is induced under anaerobic conditions via the ArcAB two-component regulation system. CsrN subsequently enhances the expression of the narGHJI operon, which encodes a nitrate reductase complex. This promotes the colonization of C. sakazakii in the gastrointestinal tract and benefits its survival within macrophages, ultimately leading to increased systemic bacterial dissemination and virulence in the host. We show that administration of tungstate, a specific inhibitor of nitrate respiration, significantly attenuates C. sakazakii virulence in animal experiments. This work provides novel insights into the survival and pathogenicity mechanisms employed by C. sakazakii in host environments and suggests nitrate respiration as a potential therapeutic target for combating C. sakazakii infections.
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Data availability
RNA-seq data have been deposited in the NCBI SRA database under accession code PRJNA1278892. The proteomics data were submitted to the iProX (integrated proteome resources) (project ID: IPX0012657000). The raw sequencing data of 16S rRNA have been deposited in the Genome Sequence Archive in BIG Data Center, Beijing Institute of Genomics (BIG), Chinese Academy of Sciences, under the accession number: CRA033865. Source data are provided with this paper.
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Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (82372267 to B.L., 82402643 to H.S., W2512084 to B.L., 82572591 to B.L., 32070133 to L.F., 32470111 to L.F., 32130003 to L.W., 32370194 to L.W.), grants from the Natural Science Foundation of Shenzhen Province of China (JCYJ20220530164604010 to B.L., JCYJ20230807151559009 to B.L.), a grant from Guangdong Basic and Applied Basic Research Foundation of China (2024A1515010588 to B.L.), a grant from Key Laboratory Major Project (Tianjin) (25ZXZSSS00710 to B.L.) and a grant from Fundamental Research Funds for Central Universities of China (63233172 to B.L.).
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Conceptualization, B.L., L.W., X.L. and H.S.; methodology, X.L., H.S., X.Y., L.F., Y.N., B.X., J.Q., J.W., Z.L., L.W. and L.F.; visualization, X.L. and H.S.; supervision, B.L.; writing–original draft, B.L., L.W., X.L. and H.S.; writing– review & editing, B.L., L.W., X.L., and H.S.
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Li, X., Sun, H., Yang, X. et al. sRNA centered signaling activates nitrate respiration and enhances Cronobacter sakazakii virulence in host environments. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70257-x
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DOI: https://doi.org/10.1038/s41467-026-70257-x
