Nature Microbiology
Lukas Hafner, Enzo Gadin, Lei Huang, Arthur Frouin, Fabien Laporte, Charlotte Gaultier, Afonso Vieira, Claire Maudet, Hugo Varet , Alexandra Moura, Hélène Bracq-Dieye, Nathalie Tessaud-Rita, Mylène Maury, Melody Dazas, Rachel Legendre, Pauline Gastineau, Yu-Huan Tsai, Jean-Yves Coppée, Caroline Charlier, Etienne Patin, Rayan Chikhi, Eduardo P. C. Rocha, Alexandre Leclercq, Olivier Disson, Hugues Aschard & Marc Lecuit
Summary
Microbial pathogenesis is mediated by the expression of virulence genes. However, as microbes with identical virulence gene content can differ in their pathogenic potential, other virulence determinants must be involved. Here, by combining comparative genomics and transcriptomics of a large collection of isolates of the model pathogen Listeria monocytogenes, time-lapse microscopy, in vitro evolution and in vivo experiments, we show
that the individual stress responsiveness of L. monocytogenes isolates determines their respective levels of virulence in vivo and reflects their degree of host adaptation. The transcriptional signature that accounts for the heterogeneity in the virulence of L. monocytogenes species is mediated by the stress response regulator SigB and driven by differential stress responsiveness. The tuning of SigB pathway responsiveness is polygenic
and influenced by multiple, individually rare gene variations. This study reveals an overarching determinant of microbial virulence, challenging the paradigm of accessory virulence gene content as the major determinant of intraspecies virulence heterogeneity.
More information at DOI: https://doi.org/10.1038/s41564-024-01859-8
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