Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages

TT Tran; CD Mathmann; M Gatica-Andrades; RF Rollo; M Oelker; JK Ljungberg; TTK Nguyen; A Zamoshnikova; LK Kummari; OJK Wyer; KM Irvine; J Melo-Bolívar; A Gross; D Brown; JYW Mak; DP Fairlie; KA Hansford; MA Cooper; R Giri; V Schreiber; SR Joseph; F Simpson; TC Barnett; J Johansson; W Dankers; J Harris; TJ Wells; O Kapetanovic; MJ Sweet; EA Latomanski; HJ Newton; RJR Guérillot; A Hachani; TP Stinear; SY Ong; Y Chandran; EL Hartland; B Kobe; JL Stow; AE Sauer-Eriksson; J Begun; JC Kling; A Blumenthal

Journal article

Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages

TT Tran, CD Mathmann, M Gatica-Andrades, RF Rollo, M Oelker, JK Ljungberg, TTK Nguyen, A Zamoshnikova, LK Kummari, OJK Wyer, KM Irvine, J Melo-Bolívar, A Gross, D Brown, JYW Mak, DP Fairlie, KA Hansford, MA Cooper, R Giri, V Schreiber Show all

Plos Pathogens | PUBLIC LIBRARY SCIENCE | Published : 2022

DOI: 10.1371/journal.ppat.1010166

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Abstract

A hallmark of Listeria (L.) monocytogenes pathogenesis is bacterial escape from maturing entry vacuoles, which is required for rapid bacterial replication in the host cell cytoplasm and cell-to-cell spread. The bacterial transcriptional activator PrfA controls expression of key virulence factors that enable exploitation of this intracellular niche. The transcriptional activity of PrfA within infected host cells is controlled by allosteric coactivation. Inhibitory occupation of the coactivator site has been shown to impair PrfA functions, but consequences of PrfA inhibition for L. monocytogenes infection and pathogenesis are unknown. Here we report the crystal structure of PrfA with a small m..

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University of Melbourne Researchers

Hayley Newton Author

Romain Guérillot Author

Abdou Hachani Author

Tim Stinear Author

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Awarded by National Health and Medical Research Council

Funding Acknowledgements

This work was supported by a project grant by the National Health and Medical Research Council (NHMRC) of Australia (1142456; AB), a Postgraduate Scholarship through the Australia Awards Scholarship Program (TTT), Chilean Government Postgraduate Scholarship Becas Chile and a University of Queensland Top-up Scholarship (MGA), Postdoctoral Research Fellowship by The University of Queensland (JCK), NHMRC Senior Principal Research Fellowship (1117017; DPF), Australian Research Council (ARC) Centre of Excellence for Advanced Molecular Imaging (CE140100011; DPF), NHMRC Senior Research Fellowship (1107914; MJS), NHMRC Leadership Research Fellowships (1194406; MJS; 1176209; JLS) Horizon 2020_MSCA Global Fellowship grant (657766; AH), NHMRC project grant (1066791; TPS), NHMRC Research Fellowship (1008549; TPS), NHMRC project grant (1098820; ELH), NHMRC project grant (1160570; BK) and ARC Laureate Fellowship (FL180100109; BK), and project grant by the Swedish Research Council (AES-E). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.