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Evidence of Cross-Regulation in Two Closely Related Pyruvate-Sensing Systems in Uropathogenic Escherichia coli

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Abstract

Two-component systems (TCSs) dictate many bacterial responses to environmental change via the activation of a membrane-embedded sensor kinase, which has molecular specificity for a cognate response regulator protein. However, although the majority of TCSs operate through seemingly strict cognate protein–protein interactions, there have been several reports of TCSs that violate this classical model of signal transduction. Our group has recently demonstrated that some of these cross-interacting TCSs function in a manner that imparts a fitness advantage to bacterial pathogens. In this study, we describe interconnectivity between the metabolite-sensing TCSs YpdA/YpdB and BtsS/BtsR in uropathogenic Escherichia coli (UPEC). The YpdA/YpdB and BtsS/BtsR TCSs have been previously reported to interact in K12 E. coli, where they alter the expression of putative transporter genes yhjX and yjiY, respectively. These target genes are both upregulated in UPEC during acute and chronic murine models of urinary tract infection, as well as in response to pyruvate and serine added to growth media in vitro. Here, we show that proper regulation of yhjX in UPEC requires the presence of all components from both of these TCSs. By utilizing plasmid-encoded luciferase reporters tracking the activity of the yhjX and yjiY promoters, we demonstrate that deletions in one TCS substantially alter transcriptional activity of the opposing system’s target gene. However, unlike in K12 E. coli, single gene deletions in the YpdA/YpdB system do not alter yjiY gene expression in UPEC, suggesting that niche and lifestyle-specific pressures may be selecting for differential cross-regulation of TCSs in pathogenic and non-pathogenic E. coli.

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Acknowledgements

The authors would like to thank the members of the Hadjifrangiskou laboratory for critical review of the manuscript. B.D.S. was supported by the NIH GM07628 T32 training grant. M.N.H. was supported by NIH 5T32GM008554-22 and NIH 2R25GM062459-14 training programs. Financial support for this work was provided by the NIDDK Diabetic Complications Consortium (DiaComp, http://www.diacomp.org), Grant DK076169.

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Author notes

  1. Hamilton D. Green & Stefan Behr

    Present address: Roche Diagnostics GmbH, Nonnenwald 2, 82377, Penzberg, Germany

Authors and Affiliations

  1. Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA

    Bradley D. Steiner

  2. Division of Molecular Pathogenesis, Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, 1161 21st Avenue South, MCN A5225A, Nashville, TN, 37232, USA

    Allison R. Eberly, Melanie N. Hurst, Ellisa W. Zhang & Maria Hadjifrangiskou

  3. Munich Center for Integrated Protein Science (CIPSM) at the Department of Microbiology, Ludwig-Maximilians-Universität München, Martinsried, Germany

    Stefan Behr & Kirsten Jung

  4. Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

    Maria Hadjifrangiskou

  5. Vanderbilt Institute for Infection, Immunology & Inflammation, Nashville, TN, USA

    Maria Hadjifrangiskou

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  1. Bradley D. Steiner
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Contributions

BDS, ARE, MNH, HDG, SB, KJ, MH: conceived and designed experiments. BDS, ARE, MNH, EZ, HDG, MH: performed the experiments. KJ, SB: provided technical advice and edited the manuscript. BDS, MH: analyzed the data. BDS, ARE, MNH, MH: wrote and edited the manuscript.

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Correspondence to Maria Hadjifrangiskou.

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Steiner, B.D., Eberly, A.R., Hurst, M.N. et al. Evidence of Cross-Regulation in Two Closely Related Pyruvate-Sensing Systems in Uropathogenic Escherichia coli. J Membrane Biol 251, 65–74 (2018). https://doi.org/10.1007/s00232-018-0014-2

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  • DOI: https://doi.org/10.1007/s00232-018-0014-2

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