SPP 2330

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GROUP BERGER & BERGER / ASSOCIATED PROJECT

Bacterial host-dependent Stx2 phage stability: molecular mechanisms and impact on virulence potential

Enterohemorrhagic Escherichia coli (EHEC) are intestinal pathogenic bacteria that can lead to the life-threatening haemolytic uremic syndrome. The EHEC cardinal virulence factor is the highly potent Shiga toxin (Stx), which is encoded on lambdoid prophages. In this project, we aim to analyze the crosstalk between the Stx2 phage (fStx2) and its E. coli host with a focus on host background-dependent fStx2 stability. Preliminary data indicate that the stability of fStx2 in E. coli K-12 MG1655 lysogens is sensitive to environmental factors and partially to genetic factors. This suggests that the auto-activation of fStx2 in MG1655 is a regulated process, however different from the respective wild type backgrounds, in which the lysogenic state is much more stable. We, therefore, aim to identify so far unknown genetic factor(s) in wild type EHEC strains that stabilize(s) these phages. Furthermore, our preliminary data indicates that fStx2 carriage affects both SOS response and metabolism in bacterial host background-dependent manner. Stx production, the hallmark of EHEC pathogenicity, is dependent on the phage activation, which is SOS response-mediated, while the metabolism is an important determinant for bacteria fitness and colonization. We therefore aim to further characterize the link between fStx2 stability and virulence potential of the bacterial host.

Figure 1. The instability of the enterohemorrhagic E. coli O104:H4 Stx2 phage in E. coli K-12 MG1655 results in competitive disadvantages. Shown is a scan of a mixed colony of E. coli K-12 MG1655 rose* and E. coli K-12 MG1655 blue* (A, scale bar is 1 mm) and a mixed colony of E. coli K-12 MG1655 rose* and E. coli 12 MG1655 K-12 blue* fO104 stx2::yfp (B, scale bar is 1 mm). The lysogenisation of E. coli K-12 MG1655 blue* with the Stx2 phage of E. coli O104:H4 results in a competitive disadvantage (compare A and B). This is largely due to auto-induction of the phage in the E. coli K-12 MG1655 background, as indicated by the expression of the late phage gene stx2 by a substantial fraction of cells (YFP positive) within the patch of the lysogen E. coli 12 MG1655 blue* fO104 stx2::yfp (C, scale bar is 10 µm).

Principal Investigator(s)

Dr. Petya Berger & Dr. Michael Berger
Institut für Hygiene, Universität Münster

E-Mail: petya.berger@ukmuenster.de; michael.berger@ukmuenster.de
Homepage: https://www.medizin.uni-muenster.de/hygiene/start.html

PhD student(s)

NA

Publications

  • Peng L, Dumevi RM, Chitto M, Haarmann N, Berger P, Koudelka G, Schmidt H, Mellmann A, Dobrindt U, Berger M. A robust one-step recombineering system for enterohemorrhagic Escherichia coli. Microorganisms 2022; 10. https://doi.org/10.3390/microorganisms10091689
  • Berger P, Kouzel IU, Berger M, Haarmann N, Dobrindt U, Koudelka GB, Mellmann A. Carriage of Shiga toxin phage profoundly affects Escherichia coli gene expression and carbon source utilization. BMC Genomics 2019; 20:504. https://doi.org/10.1186/s12864-019-5892-x
  • Berger M, Aijaz I, Berger P, Dobrindt U, Koudelka G. Transcriptional and translational inhibitors block SOS response and Shiga toxin expression in enterohemorrhagic Escherichia coli. Sci Rep 2019; 9:18777. https://doi.org/10.1038/s41598-019-55332-2