Skip to main content
SpringerLink
Log in

ZntR positively regulates T6SS4 expression in Yersinia pseudotuberculosis

  • Microbial Genetics, Genomics and Molecular Biology
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

The type VI secretion system (T6SS) is a widespread and versatile protein secretion system found in most Gram-negative bacteria. Studies of T6SS have mainly focused on its role in virulence toward host cells and inter-bacterial interactions, but studies have also shown that T6SS4 in Yersinia pseudotuberculosis participates in the acquisition of zinc ions to alleviate the accumulation of hydroxyl radicals induced by multiple stressors. Here, by comparing the gene expression patterns of wild-type and zntR mutant Y. pseudotuberculosis cells using RNA-seq analysis, T6SS4 and 17 other biological processes were found to be regulated by ZntR. T6SS4 was positively regulated by ZntR in Y. pseudotuberculosis, and further investigation demonstrated that ZntR regulates T6SS4 by directly binding to its promoter region. T6SS4 expression is regulated by zinc via ZntR, which maintains intracellular zinc homeostasis and controls the concentration of reactive oxygen species to prevent bacterial death under oxidative stress. This study provides new insights into the regulation of T6SS4 by a zinc-dependent transcriptional regulator, and it provides a foundation for further investigation of the mechanism of zinc transport by T6SS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Basler, M., Pilhofer, M., Henderson, G.P., Jensen, G.J., and Mekalanos, J.J. 2012. Type VI secretion requires a dynamic contractile phage tail-like structure. Nature 483, 182–186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bingle, L.E., Bailey, C.M., and Pallen, M.J. 2008. Type VI secretion: a beginner’s guide. Curr. Opin. Microbiol. 11, 3–8.

    Article  CAS  PubMed  Google Scholar 

  • Bobrov, A.G., Kirillina, O., Fetherston, J.D., Miller, M.C., Burlison, J.A., and Perry, R.D. 2014. The Yersinia pestis siderophore, yersiniabactin, and the ZnuABC system both contribute to zinc acquisition and the development of lethal septicaemic plague in mice. Mol. Microbiol. 93, 759–775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boyer, F., Fichant, G., Berthod, J., Vandenbrouck, Y., and Attree, I. 2009. Dissecting the bacterial type VI secretion system by a genome wide in silico analysis: what can be learned from available microbial genomic resources? BMC Genom. 10, 104.

    Article  Google Scholar 

  • Brown, N.L., Stoyanov, J.V., Kidd, S.P., and Hobman, J.L. 2003. The MerR family of transcriptional regulators. FEMS Microbiol. Rev. 27, 145–163.

    Article  CAS  PubMed  Google Scholar 

  • Cascales, E. and Cambillau, C. 2012. Structural biology of type VI secretion systems. Philos. Trans. R Soc. Lond. B Biol. Sci. 367, 1102–1111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cornelis, P., Wei, Q., Andrews, S.C., and Vinckx, T. 2011. Iron homeostasis and management of oxidative stress response in bacteria. Metallomics 3, 540–549.

    Article  PubMed  Google Scholar 

  • Dong, T.G., Dong, S., Catalano, C., Moore, R., Liang, X., and Mekalanos, J.J. 2015. Generation of reactive oxygen species by lethal attacks from competing microbes. Proc. Natl. Acad. Sci. USA 112, 2181–2186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Faulkner, M.J. and Helmann, J.D. 2011. Peroxide stress elicits adaptive changes in bacterial metal ion homeostasis. Antioxid. Redox Signal. 15, 175–189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grass, G., Wong, M.D., Rosen, B.P., Smith, R.L., and Rensing, C. 2002. ZupT is a Zn(II) uptake system in Escherichia coli. J. Bacteriol. 184, 864–866.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guan, J., Xiao, X., Xu, S., Gao, F., Wang, J., Wang, T., Song, Y., Pan, J., Shen, X., and Wang, Y. 2015. Roles of RpoS in Yersinia pseudotuberculosis stress survival, motility, biofilm formation and type VI secretion system expression. J. Microbiol. 53, 633–642.

    Article  CAS  PubMed  Google Scholar 

  • Gueguen, E., Durand, E., Zhang, X.Y., d’Amalric, Q., Journet, L., and Cascales, E. 2013. Expression of a Type VI secretion system is responsive to envelope stresses through the OmpR transcriptional activator. PLoS One 8, e66615.

    Article  Google Scholar 

  • Holland, I.B. 2010. The extraordinary diversity of bacterial protein secretion mechanisms. Methods Mol. Biol. 619, 1–20.

    Article  CAS  PubMed  Google Scholar 

  • Ishikawa, T., Sabharwal, D., Broms, J., Milton, D.L., Sjostedt, A., Uhlin, B.E., and Wai, S.N. 2012. Pathoadaptive conditional regulation of the type VI secretion system in Vibrio cholerae O1 strains. Infect. Immun. 80, 575–584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jani, A.J. and Cotter, P.A. 2010. Type VI secretion: not just for pathogenesis anymore. Cell Host Microbe 8, 2–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanehisa, M., Araki, M., Goto, S., Hattori, M., Hirakawa, M., Itoh, M., Katayama, T., Kawashima, S., Okuda, S., Tokimatsu, T., et al. 2008. KEGG for linking genomes to life and the environment. Nucleic Acids Res. 36, D480–484.

    Article  CAS  PubMed  Google Scholar 

  • Khan, S., Brocklehurst, K.R., Jones, G.W., and Morby, A.P. 2002. The functional analysis of directed amino-acid alterations in ZntR from Escherichia coli. Biochem. Biophys. Res. Commun. 299, 438–445.

    Article  CAS  PubMed  Google Scholar 

  • Li, B. and Dewey, C.N. 2011. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform. 12, 323.

    Article  CAS  Google Scholar 

  • Li, H. and Durbin, R. 2009. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma, L.S., Hachani, A., Lin, J.S., Filloux, A., and Lai, E.M. 2014. Agrobacterium tumefaciens deploys a superfamily of type VI secretion DNase effectors as weapons for interbacterial competition in planta. Cell Host Microbe 16, 94–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma, A.T., McAuley, S., Pukatzki, S., and Mekalanos, J.J. 2009. Translocation of a Vibrio cholerae type VI secretion effector requires bacterial endocytosis by host cells. Cell Host Microbe 5, 234–243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller, J.H. 1992. A short course in bacterial genetics: a laboratory manual and handbook for Escherichia coli and related bacteria. Cold Spring Harbor Laboratory Press, Plainview, N.Y., USA.

    Google Scholar 

  • Mols, M. and Abee, T. 2011. Primary and secondary oxidative stress in Bacillus. Environ. Microbiol. 13, 1387–1394.

    Article  CAS  PubMed  Google Scholar 

  • Mortazavi, A., Williams, B.A., McCue, K., Schaeffer, L., and Wold, B. 2008. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nature Methods 5, 621–628.

    Article  CAS  PubMed  Google Scholar 

  • Mougous, J.D., Cuff, M.E., Raunser, S., Shen, A., Zhou, M., Gifford, C.A., Goodman, A.L., Joachimiak, G., Ordonez, C.L., Lory, S., et al. 2006. A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science 312, 1526–1530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mougous, J.D., Gifford, C.A., Ramsdell, T.L., and Mekalanos, J.J. 2007. Threonine phosphorylation post-translationally regulates protein secretion in Pseudomonas aeruginosa. Nature Cell Biol. 9, 797–803.

    Article  CAS  PubMed  Google Scholar 

  • Outten, C.E. and O’Halloran, T.V. 2001. Femtomolar sensitivity of metalloregulatory proteins controlling zinc homeostasis. Science 292, 2488–2492.

    Article  CAS  PubMed  Google Scholar 

  • Outten, C.E., Outten, F.W., and O’Halloran, T.V. 1999. DNA distortion mechanism for transcriptional activation by ZntR, a Zn(II)-responsive MerR homologue in Escherichia coli. J. Biol. Chem. 274, 37517–37524.

    Article  CAS  PubMed  Google Scholar 

  • Panina, E.M., Mironov, A.A., and Gelfand, M.S. 2003. Comparative genomics of bacterial zinc regulons: enhanced ion transport, pathogenesis, and rearrangement of ribosomal proteins. Proc. Natl. Acad. Sci. USA 100, 9912–9917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parsons, D.A. and Heffron, F. 2005. sciS, an icmF homolog in Salmonella enterica serovar Typhimurium, limits intracellular replication and decreases virulence. Infect. Immun. 73, 4338–4345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patzer, S.I. and Hantke, K. 1998. The ZnuABC high-affinity zinc uptake system and its regulator Zur in Escherichia coli. Mol. Microbiol. 28, 1199–1210.

    Article  CAS  PubMed  Google Scholar 

  • Permina, E.A., Kazakov, A.E., Kalinina, O.V., and Gelfand, M.S. 2006. Comparative genomics of regulation of heavy metal resistance in Eubacteria. BMC Microbiol. 6, 49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petrarca, P., Ammendola, S., Pasquali, P., and Battistoni, A. 2010. The Zur-regulated ZinT protein is an auxiliary component of the high-affinity ZnuABC zinc transporter that facilitates metal recruitment during severe zinc shortage. J. Bacteriol. 192, 1553–1564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pruteanu, M., Neher, S.B., and Baker, T.A. 2007. Ligand-controlled proteolysis of the Escherichia coli transcriptional regulator ZntR. J. Bacteriol. 189, 3017–3025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pukatzki, S., Ma, A.T., Sturtevant, D., Krastins, B., Sarracino, D., Nelson, W.C., Heidelberg, J.F., and Mekalanos, J.J. 2006. Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system. Proc. Natl. Acad. Sci. USA 103, 1528–1533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rensing, C., Mitra, B., and Rosen, B.P. 1997. The zntA gene of Escherichia coli encodes a Zn(II)-translocating P-type ATPase. Proc. Natl. Acad. Sci. USA 94, 14326–14331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Russell, A.B., Hood, R.D., Bui, N.K., LeRoux, M., Vollmer, W., and Mougous, J.D. 2011. Type VI secretion delivers bacteriolytic effectors to target cells. Nature 475, 343–347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Russell, A.B., Wexler, A.G., Harding, B.N., Whitney, J.C., Bohn, A.J., Goo, Y.A., Tran, B.Q., Barry, N.A., Zheng, H., Peterson, S.B., et al. 2014. A type VI secretion-related pathway in Bacteroidetes mediates interbacterial antagonism. Cell Host Microbe 16, 227–236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song, Y., Xiao, X., Li, C., Wang, T., Zhao, R., Zhang, W., Zhang, L., Wang, Y., and Shen, X. 2015. The dual transcriptional regulator RovM regulates the expression of AR3- and T6SS4-dependent acid survival systems in response to nutritional status in Yersinia pseudotuberculosis. Environ. Microbiol. 17, 4631–4645.

    Article  CAS  PubMed  Google Scholar 

  • Tarazona, S., Garcia-Alcalde, F., Dopazo, J., Ferrer, A., and Conesa, A. 2011. Differential expression in RNA-seq: a matter of depth. Genome Res. 21, 2213–2223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, D., Hosteen, O., and Fierke, C.A. 2012. ZntR-mediated transcription of zntA responds to nanomolar intracellular free zinc. J. Inorg. Biochem. 111, 173–181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, T.T., Si, M.R., Song, Y.H., Zhu, W.H., Gao, F., Wang, Y., Zhang, L., Zhang, W.P., Wei, G.H., Luo, Z.Q., et al. 2015. Type VI secretion system transports Zn2+ to combat multiple stresses and host immunity. PLoS Pathog. 11, e1005020.

    Article  Google Scholar 

  • Weber, B., Hasic, M., Chen, C., Wai, S.N., and Milton, D.L. 2009. Type VI secretion modulates quorum sensing and stress response in Vibrio anguillarum. Environ. Microbiol. 11, 3018–3028.

    Article  CAS  PubMed  Google Scholar 

  • Wu, C.F., Lin, J.S., Shaw, G.C., and Lai, E.M. 2012. Acid-induced type VI secretion system is regulated by ExoR-ChvG/ChvI signaling cascade in Agrobacterium tumefaciens. PLoS Pathog. 8, e1002938.

    Article  Google Scholar 

  • Zhang, W., Wang, Y., Song, Y., Wang, T., Xu, S., Peng, Z., Lin, X., Zhang, L., and Shen, X. 2013. A type VI secretion system regulated by OmpR in Yersinia pseudotuberculosis functions to maintain intracellular pH homeostasis. Environ. Microbiol. 15, 557–569.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, W., Xu, S., Li, J., Shen, X., Wang, Y., and Yuan, Z. 2011. Modulation of a thermoregulated type VI secretion system by AHLdependent quorum sensing in Yersinia pseudotuberculosis. Arch. Microbiol. 193, 351–363.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, P. R. China

    Tietao Wang, Keqi Chen, Fen Gao, Yiwen Kang, Zhuo Wang, Yao Wang & Xihui Shen

  2. Environmental Analytical Laboratory, National Physical and Standards Laboratory, PCSIR, Islamabad, Pakistan

    Muhammad Tausif Chaudhry

Authors
  1. Tietao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keqi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fen Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yiwen Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Muhammad Tausif Chaudhry
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhuo Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xihui Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yao Wang or Xihui Shen.

Additional information

These authors contributed equally to this work.

Supplemental material for this article may be found at http://www.springerlink.com/content/120956.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, T., Chen, K., Gao, F. et al. ZntR positively regulates T6SS4 expression in Yersinia pseudotuberculosis . J Microbiol. 55, 448–456 (2017). https://doi.org/10.1007/s12275-017-6540-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-017-6540-2

Keywords

Search

Navigation