Legionella para-effectors target chromatin and promote bacterial replication

Daniel Schator, Sonia Mondino, Jérémy Berthelet, Cristina Silvestre, Mathilde Assaya, Christophe Rusniok, Fernando Rodrigues-Lima, Annemarie Wehenkel, Carmen Buchrieser () and Monica Rolando ()
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Daniel Schator: Université Paris Cité, CNRS UMR 6047, Biologie des Bactéries Intracellulaires
Sonia Mondino: Université Paris Cité, CNRS UMR 6047, Biologie des Bactéries Intracellulaires
Jérémy Berthelet: Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative
Cristina Silvestre: Université Paris Cité, CNRS UMR 6047, Biologie des Bactéries Intracellulaires
Mathilde Assaya: Université Paris Cité, CNRS UMR 3528, Unité de Microbiologie Structurale
Christophe Rusniok: Université Paris Cité, CNRS UMR 6047, Biologie des Bactéries Intracellulaires
Fernando Rodrigues-Lima: Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative
Annemarie Wehenkel: Université Paris Cité, CNRS UMR 3528, Unité de Microbiologie Structurale
Carmen Buchrieser: Université Paris Cité, CNRS UMR 6047, Biologie des Bactéries Intracellulaires
Monica Rolando: Université Paris Cité, CNRS UMR 6047, Biologie des Bactéries Intracellulaires

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Legionella pneumophila replicates intracellularly by secreting effectors via a type IV secretion system. One of these effectors is a eukaryotic methyltransferase (RomA) that methylates K14 of histone H3 (H3K14me3) to counteract host immune responses. However, it is not known how L. pneumophila infection catalyses H3K14 methylation as this residue is usually acetylated. Here we show that L. pneumophila secretes a eukaryotic-like histone deacetylase (LphD) that specifically targets H3K14ac and works in synergy with RomA. Both effectors target host chromatin and bind the HBO1 histone acetyltransferase complex that acetylates H3K14. Full activity of RomA is dependent on the presence of LphD as H3K14 methylation levels are significantly decreased in a ∆lphD mutant. The dependency of these two chromatin-modifying effectors on each other is further substantiated by mutational and virulence assays revealing that the presence of only one of these two effectors impairs intracellular replication, while a double knockout (∆lphD∆romA) can restore intracellular replication. Uniquely, we present evidence for “para-effectors”, an effector pair, that actively and coordinately modify host histones to hijack the host response. The identification of epigenetic marks modulated by pathogens has the potential to lead to the development of innovative therapeutic strategies to counteract bacterial infection and strengthening host defences.

Date: 2023
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DOI: 10.1038/s41467-023-37885-z

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