Reprogramming of bacterial virulence by lysine acetylation Article Swipe

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Michael Lammers , Ole Schmöker , Britta Girbardt , Sabrina Schulze , Gottfried J. Palm , Leona Berndt , Jens Hoppen , N. Kara , Xenia Schöps , Ruba Al‐Abdulla , Klara Garz , Heike Junker , Sophie Möller , Leif Steil , Christian Hentschker , Katrin Schoknecht , Lea-Maria Mayer , Vanessa Boll , Mark Doerr , Stefan Kemnitz , Kay Hofmann , Uwe T. Bornscheuer , Uwe Völker , Elke Krüger , Vera Kozjak‐Pavlovic , Leonie Speth ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.21203/rs.3.rs-6983025/v1

Gram-negative bacteria use a plethora of virulence factors to infect eukaryotic cells. CE-clan protease-related virulence factors were reported to act as deubiquitinases/ubiquitin-like specific proteases. Some have an additional acetyltransferase activity. The molecular mechanisms underlying this dual activity and the physiological consequences are only marginally understood. Here, we report crystal structures for the Simkania negevensis virulence factor SnCE1 in apo-states and in complex with SUMO1. We confirm SnCE1 acting as an efficient deSUMOylase and discover an intrinsic autoacetyltransferase activity. Acetylation impairs SnCE1 tetramer formation and as a consequence being structurally incompatible with SUMO1 binding. We provide a model for regulation of SnCE1-mediated virulence by lysine acetylation modulating autoproteolytic processing and subcellular distribution in the host cell. SnCE1 localizes to the endoplasmic reticulum in human cells and results in formation of fragmented mitochondria. Our data provide mechanistic insights how lysine acetylation of virulence factors is used to reprogram virulence adjusting it to the host cells’ metabolic state.

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Lysine Acetylation Reprogramming Virulence Microbiology Chemistry Biology Biochemistry Amino acid Gene

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Type: preprint
Language: en
Landing Page: https://doi.org/10.21203/rs.3.rs-6983025/v1
PDF: https://www.researchsquare.com/article/rs-6983025/latest.pdf
OA Status: gold
Related Works: 10
OpenAlex ID: https://openalex.org/W4411974401

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DOI: https://doi.org/10.21203/rs.3.rs-6983025/v1

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Title: Reprogramming of bacterial virulence by lysine acetylation

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Type: preprint

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Language: en

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Publication year: 2025

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Publication date: 2025-07-03

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Authors: Michael Lammers, Ole Schmöker, Britta Girbardt, Sabrina Schulze, Gottfried J. Palm, Leona Berndt, Jens Hoppen, N. Kara, Xenia Schöps, Ruba Al‐Abdulla, Klara Garz, Heike Junker, Sophie Möller, Leif Steil, Christian Hentschker, Katrin Schoknecht, Lea-Maria Mayer, Vanessa Boll, Mark Doerr, Stefan Kemnitz, Kay Hofmann, Uwe T. Bornscheuer, Uwe Völker, Elke Krüger, Vera Kozjak‐Pavlovic, Leonie Speth

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Landing page: https://doi.org/10.21203/rs.3.rs-6983025/v1

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Concepts: Lysine, Acetylation, Reprogramming, Virulence, Microbiology, Chemistry, Biology, Biochemistry, Amino acid, Gene

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