Imperial College London


Faculty of MedicineDepartment of Infectious Disease

Research Associate







Flowers buildingSouth Kensington Campus





Publication Type

3 results found

Tabib-Salazar A, Mulvenna N, Severinov K, Matthews SJ, Wigneshweraraj Set al., 2019, Xenogeneic regulation of the bacterial transcription machinery, Journal of Molecular Biology, Vol: 431, Pages: 4078-4092, ISSN: 0022-2836

The parasitic life cycle of viruses involves the obligatory subversion of the host's macromolecular processes for efficient viral progeny production. Viruses that infect bacteria, bacteriophages (phages), are no exception and have evolved sophisticated ways to control essential biosynthetic machineries of their bacterial prey to benefit phage development. The xenogeneic regulation of bacterial cell function is a poorly understood area of bacteriology. The activity of the bacterial transcription machinery, the RNA polymerase (RNAP), is often regulated by a variety of mechanisms involving small phage-encoded proteins. In this review, we provide a brief overview of known phage proteins that interact with the bacterial RNAP and compare how two prototypical phages of Escherichia coli, T4 and T7, use small proteins to 'puppeteer' the bacterial RNAP to ensure a successful infection.

Journal article

Tabib-Salazar A, Liu B, Declan B, Burchell L, Qimron U, Matthews S, Wigneshweraraj Set al., 2018, T7 phage factor required for managing RpoS in Escherichia coli, Proceedings of the National Academy of Sciences, Vol: 115, Pages: E5353-E5362, ISSN: 0027-8424

T7 development in Escherichia coli requires the inhibition of the housekeepingform of the bacterial RNA polymerase (RNAP), Eσ70, by two T7 proteins: Gp2and Gp5.7. While the biological role of Gp2 is well understood, that of Gp5.7remains to be fully deciphered. Here, we present results from functional andstructural analyses to reveal that Gp5.7 primarily serves to inhibit EσS, thepredominant form of the RNAP in the stationary phase of growth, whichaccumulates in exponentially growing E. coli as a consequence of buildup ofguanosine pentaphosphate ((p)ppGpp) during T7 development. We furtherdemonstrate a requirement of Gp5.7 for T7 development in E. coli cells in thestationary phase of growth. Our finding represents a paradigm for how somelytic phages have evolved distinct mechanisms to inhibit the bacterialtranscription machinery to facilitate phage development in bacteria in theexponential and stationary phases of growth.

Journal article

Tabib-Salazar A, Liu B, Shadrin A, Burchell L, Wang Z, Wang Z, Goren MG, Yosef I, Qimron U, Severinov K, Matthews SJ, Wigneshweraraj Set al., 2017, Full shut-off of Escherichia coli RNA-polymerase by T7 phage requires a small phage-encoded DNA-binding protein, Nucleic Acids Research, Vol: 45, Pages: 7697-7707, ISSN: 1362-4962

Infection of Escherichia coli by the T7 phage leads to rapid and selective inhibition of the bacterial RNA polymerase (RNAP) by the 7 kDa T7 protein Gp2. We describe the identification and functional and structural characterisation of a novel 7 kDa T7 protein, Gp5.7, which adopts a winged helix-turn-helix-like structure and specifically represses transcription initiation from host RNAP-dependent promoters on the phage genome via a mechanism that involves interaction with DNA and the bacterial RNAP. Whereas Gp2 is indispensable for T7 growth in E. coli, we show that Gp5.7 is required for optimal infection outcome. Our findings provide novel insights into how phages fine-tune the activity of the host transcription machinery to ensure both successful and efficient phage progeny development.

Journal article

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