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Regulator of ribonuclease activity modulates the pathogenicity of Vibrio vulnificus

  • Microbial Pathogenesis and Host-Microbe Interaction
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Abstract

RraA, a protein regulator of RNase E activity, plays a unique role in modulating the mRNA abundance in Escherichia coli. The marine pathogenic bacterium Vibrio vulnificus also possesses homologs of RNase E (VvRNase E) and RraA (VvRraA1 and VvRraA2). However, their physiological roles have not yet been investigated. In this study, we demonstrated that VvRraA1 expression levels affect the pathogenicity of V. vulnificus. Compared to the wild-type strain, the VvrraA1-deleted strain (ΔVvrraA1) showed decreased motility, invasiveness, biofilm formation ability as well as virulence in mice; these phenotypic changes of ΔVvrraA1 were restored by the exogenous expression of VvrraA1. Transcriptomic analysis indicated that VvRraA1 expression levels affect the abundance of a large number of mRNA species. Among them, the half-lives of mRNA species encoding virulence factors (e.g., smcR and htpG) that have been previously shown to affect VvrraA1 expression-dependent phenotypes were positively correlated with VvrraA1 expression levels. These findings suggest that VvRraA1 modulates the pathogenicity of V. vulnificus by regulating the abundance of a subset of mRNA species.

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References

  • Aït-Bara, S., Carpousis, A.J., and Quentin, Y. 2015. RNase E in the γ-Proteobacteria: conservation of intrinsically disordered non-catalytic region and molecular evolution of microdomains. Mol. Genet. Genomics 290, 847–862.

    Article  PubMed  Google Scholar 

  • Blomfield, I.C., Vaughn, V., Rest, R.F., and Eisenstein, B.I. 1991. Allelic exchange in Escherichia coli using the Bacillus subtilis sacB gene and a temperature-sensitive pSC101 replicon. Mol. Microbiol. 5, 1447–1457.

    Article  CAS  PubMed  Google Scholar 

  • Costerton, J.W., Stewart, P.S., and Greenberg, E.P. 1999. Bacterial biofilms: a common cause of persistent infections. Science 284, 1318–1322.

    Article  CAS  PubMed  Google Scholar 

  • Donlan, R.M. 2001. Biofilm formation: a clinically relevant microbiological process. Clin. Infect. Dis. 33, 1387–1392.

    Article  CAS  PubMed  Google Scholar 

  • Grudniak, A.M., Klecha, B., and Wolska, K.I. 2018. Effects of null mutation of the heat-shock gene htpG on the production of virulence factors by Pseudomonas aeruginosa. Future Microbiol. 13, 69–80.

    Article  CAS  PubMed  Google Scholar 

  • Gulig, P.A., Bourdage, K.L., and Starks, A.M. 2005. Molecular pathogenesis of Vibrio vulnificus. J. Microbiol. 43, 118–131.

    CAS  PubMed  Google Scholar 

  • Han, Y. and Lee, E.J. 2020. Detecting Salmonella type II flagella production by transmission electron microscopy and immunocytochemistry. J. Microbiol. 58, 245–251.

    Article  CAS  PubMed  Google Scholar 

  • Heo, J., Kim, D., Joo, M., Lee, B., Seo, S., Lee, J., Song, S., Yeom, J.H., Ha, N.C., and Lee, K. 2016. RraAS2 requires both scaffold domains of RNase ES for high-affinity binding and inhibitory action on the ribonucleolytic activity. J. Microbiol. 54, 660–666.

    Article  CAS  PubMed  Google Scholar 

  • Jones, M.K. and Oliver, J.D. 2009. Vibrio vulnificus: disease and pathogenesis. Infect. Immun. 77, 1723–1733.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung, S., Park, O.J., Kim, A.R., Ahn, K.B., Lee, D., Kum, K.Y., Yun, C.H., and Han, S.H. 2019. Lipoteichoic acids of lactobacilli inhibit Enterococcus faecalis biofilm formation and disrupt the preformed biofilm. J. Microbiol. 57, 310–315.

    Article  CAS  PubMed  Google Scholar 

  • Keen, N.T., Tamaki, S., Kobayashi, D., and Trollinger, D. 1988. Improved broad-host-range plasmids for DNA cloning in Gramnegative bacteria. Gene 70, 191–197.

    Article  CAS  PubMed  Google Scholar 

  • Kim, D., Kim, Y.H., Jang, J., Yeom, J.H., Jun, J.W., Hyun, S., and Lee, K. 2016. Functional analysis of Vibrio vulnificus orthologs of Escherichia coli RraA and RNase E. Curr. Microbiol. 72, 716–722.

    Article  CAS  PubMed  Google Scholar 

  • Kim, S.Y. and Ko, K.S. 2020. Cryptic prophages in a blaNDM-1-bearing plasmid increase bacterial survival against high NaCl concentration, high and low temperatures, and oxidative and immunological stressors. J. Microbiol. 58, 483–488.

    Article  CAS  PubMed  Google Scholar 

  • Kim, S.M., Lee, D.H., and Choi, S.H. 2012. Evidence that the Vibrio vulnificus flagellar regulator FlhF is regulated by a quorum sensing master regulator SmcR. Microbiology 158, 2017–2025.

    Article  CAS  PubMed  Google Scholar 

  • Kim, H.S., Lee, M.A., Chun, S.J., Park, S.J., and Lee, K.H. 2007. Role of NtrC in biofilm formation via controlling expression of the gene encoding an ADP-glycero-manno-heptose-6-epimerase in the pathogenic bacterium, Vibrio vulnificus. Mol. Microbiol. 63, 559–574.

    Article  CAS  PubMed  Google Scholar 

  • Kim, S.Y., Lee, S.E., Kim, Y.R., Kim, C.M., Ryu, P.Y., Choy, H.E., Chung, S.S., and Rhee, J.H. 2003. Regulation of Vibrio vulnificus virulence by the LuxS quorum-sensing system. Mol. Microbiol. 48, 1647–1664.

    Article  CAS  PubMed  Google Scholar 

  • Kim, H.S., Park, S.J., and Lee, K.H. 2009. Role of NtrC-regulated exopolysaccharides in the biofilm formation and pathogenic interaction of Vibrio vulnificus. Mol. Microbiol. 74, 436–453.

    Article  CAS  PubMed  Google Scholar 

  • Kim, S.M., Park, J.H., Lee, H.S., Kim, W.B., Ryu, J.M., Han, H.J., and Choi, S.H. 2013a. LuxR homologue SmcR is essential for Vibrio vulnificus pathogenesis and biofilm detachment, and its expression is induced by host cells. Infect. Immun. 81, 3721–3730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, I.H., Wen, Y., Son, J.S., Lee, K.H., and Kim, K.S. 2013b. The fur-iron complex modulates expression of the quorum-sensing master regulator, SmcR, to control expression of virulence factors in Vibrio vulnificus. Infect. Immun. 81, 2888–2898.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, J., Lee, D.H., Jeon, C.O., and Lee, K. 2019. RNase G controls tpiA mRNA abundance in response to oxygen availability in Escherichia coli. J. Microbiol. 57, 910–917.

    Article  CAS  PubMed  Google Scholar 

  • Lee, J.H., Rhee, J.E., Park, U., Ju, H.M., Lee, B.C., Kim, T.S., Jeong, H.S., and Choi, S.H. 2007. Identification and functional analysis of Vibrio vulnificus SmcR, a novel global regulator. J. Microbiol. Biotechnol. 17, 325–334.

    CAS  PubMed  Google Scholar 

  • Lee, M., Ryu, M., Joo, M., Seo, Y.J., Lee, J., Kim, H.M., Shin, E., Yeom, J.H., Kim, Y.H., Bae, J., et al. 2021. Endoribonuclease-mediated control of hns mRNA stability constitutes a key regulatory pathway for Salmonella Typhimurium pathogenicity island 1 expression. PLoS Pathog. 17, e1009263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, M., Yeom, J.H., Jeon, C.O., and Lee, K. 2011. Studies on a Vibrio vulnificus functional ortholog of Escherichia coli RNase E imply a conserved function of RNase E-like enzymes in bacteria. Curr. Microbiol. 62, 861–865.

    Article  CAS  PubMed  Google Scholar 

  • Lee, M., Yeom, J.H., Sim, S.H., Ahn, S., and Lee, K. 2009. Effects of Escherichia coli RraA orthologs of Vibrio vulnificus on the ribonucleolytic activity of RNase E in vivo. Curr. Microbiol. 58, 349–353.

    Article  CAS  PubMed  Google Scholar 

  • Lee, K., Zhan, X., Gao, J., Qiu, J., Feng, Y., Meganathan, R., Cohen, S.N., and Georgiou, G. 2003. RraA: a protein inhibitor of RNase E activity that globally modulates RNA abundance in E. coli. Cell 114, 623–634.

    CAS  PubMed  Google Scholar 

  • Li, G. and Wang, M.Y. 2020. The role of Vibrio vulnificus virulence factors and regulators in its infection-induced sepsis. Folia Microbiol. 65, 265–274.

    Article  CAS  Google Scholar 

  • Li, X., Zhou, Y., Jiang, Q., Yang, H., Pi, D., Liu, X., Gao, X., Chen, N., and Zhang, X. 2019. Virulence properties of Vibrio vulnificus isolated from diseased zoea of freshness shrimp Macrobrachium rosenbergii. Microb. Pathog. 127, 166–171.

    Article  CAS  PubMed  Google Scholar 

  • López-Pérez, M., Jayakumar, J.M., Haro-Moreno, J.M., Zaragoza-Solas, A., Reddi, G., Rodriguez-Valera, F., Shapiro, O.H., Alam, M., and Almagro-Moreno, S. 2019. Evolutionary model of cluster divergence of the emergent marine pathogen Vibrio vulnificus: from genotype to ecotype. mBio 10, e02852-18.

  • Milton, D.L., O’Toole, R., Horstedt, P., and Wolf-Watz, H. 1996. Flagellin A is essential for the virulence of Vibrio anguillarum. J. Bacteriol. 178, 1310–1319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monzingo, A.F., Gao, J., Qiu, J., Georgiou, G., and Robertus, J.D. 2003. The X-ray structure of Escherichia coli RraA (MenG), A protein inhibitor of RNA processing. J. Mol. Biol. 332, 1015–1024.

    Article  CAS  PubMed  Google Scholar 

  • Moore, C.J., Go, H., Shin, E., Ha, H.J., Song, S., Ha, N.C., Kim, Y.H., Cohen, S.N., and Lee, K. 2021. Substrate-dependent effects of quaternary structure on RNase E activity. Genes Dev. 35, 286–299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Na, D. 2020. User guides for biologists to learn computational methods. J. Microbiol. 58, 173–175.

    Article  PubMed  Google Scholar 

  • Oliver, J.D. 2015. The biology of Vibrio vulnificus. Microbiol. Spectr. 3, 3.3.01.

    Article  Google Scholar 

  • Park, S.J., Lim, S., and Choi, J.I. 2020. Improved tolerance of Escherichia coli to oxidative stress by expressing putative response regulator homologs from Antarctic bacteria. J. Microbiol. 58, 131–141.

    Article  CAS  PubMed  Google Scholar 

  • Perwez, T. and Kushner, S.R. 2006. RNase Z in Escherichia coli plays a significant role in mRNA decay. Mol. Microbiol. 60, 723–737.

    Article  CAS  PubMed  Google Scholar 

  • Raz, N., Danin-Poleg, Y., Hayman, R.B., Bar-On, Y., Linetsky, A., Shmoish, M., Sanjuán, E., Amaro, C., Walt, D.R., and Kashi, Y. 2014. Genome-wide SNP-genotyping array to study the evolution of the human pathogen Vibrio vulnificus biotype 3. PLoS ONE 9, e114576.

    Article  PubMed  PubMed Central  Google Scholar 

  • Seo, S., Kim, D., Song, W., Heo, J., Joo, M., Lim, Y., Yeom, J.H., and Lee, K. 2017. RraAS1 inhibits the ribonucleolytic activity of RNase ES by interacting with its catalytic domain in Streptomyces coelicolor. J. Microbiol. 55, 37–43.

    Article  CAS  PubMed  Google Scholar 

  • Sheehan, L.M., Budnick, J.A., Fyffe-Blair, J., King, K.A., Settlage, R.E., and Caswell, C.C. 2020. The endoribonuclease RNase E coordinates expression of mRNAs and small regulatory RNAs and is critical for the virulence of Brucella abortus. J. Bacteriol. 202, e00240–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simon, R., Priefer, U., and Pühler, A. 1983. A broad host range mobilization system for in vivo genetic engineering: transposon mutagenesis in Gram negative bacteria. Nat. Biotechnol. 1, 784–791.

    Article  CAS  Google Scholar 

  • Song, S., Hong, S., Jang, J., Yeom, J.H., Park, N., Lee, J., Lim, Y., Jeon, J.Y., Choi, H.K., Lee, M., et al. 2017. Functional implications of hexameric assembly of RraA proteins from Vibrio vulnificus. PLoS ONE 12, e0190064.

    Article  PubMed  PubMed Central  Google Scholar 

  • Song, W., Joo, M., Yeom, J.H., Shin, E., Lee, M., Choi, H.K., Hwang, J., Kim, Y.I., Seo, R., Lee, J.E., et al. 2019. Divergent rRNAs as regulators of gene expression at the ribosome level. Nat. Microbiol. 4, 515–526.

    Article  CAS  PubMed  Google Scholar 

  • Stead, M.B., Marshburn, S., Mohanty, B.K., Mitra, J., Pena Castillo, L., Ray, D., van Bakel, H., Hughes, T.R., and Kushner, S.R. 2011. Analysis of Escherichia coli RNase E and RNase III activity in vivo using tiling microarrays. Nucleic Acids Res. 39, 3188–3203.

    Article  CAS  PubMed  Google Scholar 

  • Thuraisamy, T. and Lodato, P.B. 2018. Influence of RNase E deficiency on the production of stx2-bearing phages and Shiga toxin in an RNase E-inducible strain of enterohaemorrhagic Escherichia coli (EHEC) O157:H7. J. Med. Microbiol. 67, 724–732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whon, T.W., Shin, N.R., Kim, J.Y., and Roh, S.W. 2021. Omics in gut microbiome analysis. J. Microbiol. 59, 292–297.

    Article  PubMed  Google Scholar 

  • Wright, A.C., Simpson, L.M., Oliver, J.D., and Morris, J.G. Jr. 1990. Phenotypic evaluation of acapsular transposon mutants of Vibrio vulnificus. Infect. Immun. 58, 1769–1773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang, J., Jain, C., and Schesser, K. 2008. RNase E regulates the Yersinia type 3 secretion system. J. Bacteriol. 190, 3774–3778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yeom, J.H., Lee, B., Kim, D., Lee, J.K., Kim, S., Bae, J., Park, Y., and Lee, K. 2016. Gold nanoparticle-DNA aptamer conjugate-assisted delivery of antimicrobial peptide effectively eliminates intracellular Salmonella enterica serovar Typhimurium. Biomaterials 104, 43–51.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, M., Zhou, L., Kawarasaki, Y., and Georgiou, G. 2006. Regulation of RraA, a protein inhibitor of RNase E-mediated RNA decay. J. Bacteriol. 188, 3257–3263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhi, Y., Lin, S.M., Jang, A.Y., Ahn, K.B., Ji, H.J., Guo, H.C., Lim, S., and Seo, H.S. 2019. Effective mucosal live attenuated Salmonella vaccine by deleting phosphotransferase system component genes ptsI and crr. J. Microbiol. 57, 64–73.

    Article  CAS  PubMed  Google Scholar 

  • Ziolo, K.J., Jeong, H.G., Kwak, J.S., Yang, S., Lavker, R.M., and Satchell, K.J. 2014. Vibrio vulnificus biotype 3 multifunctional auto-processing RTX toxin is an adenylate cyclase toxin essential for virulence in mice. Infect. Immun. 82, 2148–2157.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This research was supported by the Chung-Ang University Graduate Research Scholarship in 2020 and the National Research Foundation of Korea (grant no. NRF-2021R1A2-C3008934 to K. L.).

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Correspondence to Minho Lee or Kangseok Lee.

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Conflict of Interest The authors have declared that no competing interests exist.

Ethical Statements All animal experiments were performed in accordance with the National Guidelines for the Use of Animals in Scientific Research and were approved by the Chung-Ang University Support Center (Approval No. CAU2012-0044).

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Lee, J., Shin, E., Park, J. et al. Regulator of ribonuclease activity modulates the pathogenicity of Vibrio vulnificus. J Microbiol. 59, 1133–1141 (2021). https://doi.org/10.1007/s12275-021-1518-5

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