Occurrence and repair of alkylating stress in the intracellular pathogen Brucella abortus

Katy Poncin; Agnès Roba; Ravikumar Jimmidi; Georges Potemberg; Antonella Fioravanti; Nayla Francis; Kévin Willemart; Nicolas Zeippen; Arnaud Machelart; Emanuele G. Biondi; Eric Muraille; Stéphane P. Vincent; Xavier De Bolle

doi:10.1038/s41467-019-12516-8

Occurrence and repair of alkylating stress in the intracellular pathogen Brucella abortus

Katy Poncin, Agnès Roba, Ravikumar Jimmidi, Georges Potemberg, Antonella Fioravanti, Nayla Francis, Kévin Willemart, Nicolas Zeippen, Arnaud Machelart, Emanuele G. Biondi, Eric Muraille, Stéphane P. Vincent, Xavier De Bolle

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Abstract

It is assumed that intracellular pathogenic bacteria have to cope with DNA alkylating stress within host cells. Here we use single-cell reporter systems to show that the pathogen Brucella abortus does encounter alkylating stress during the first hours of macrophage infection. Genes encoding direct repair and base-excision repair pathways are required by B. abortus to face this stress in vitro and in a mouse infection model. Among these genes, ogt is found to be under the control of the conserved cell-cycle transcription factor GcrA. Our results highlight that the control of DNA repair in B. abortus displays distinct features that are not present in model organisms such as Escherichia coli.

Original language	English
Article number	4847
Pages (from-to)	4847
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12516-8
Publication status	Published - 24 Oct 2019

Funding

We thank members of the URBM and I. Matic for stimulating discussions. We also thank Y. Ashhab for his help regarding ChIP-seq analysis. We thank H. Lavender and C. M. Tang for their careful reading of our manuscript. We thank UNamur (https://www.unamur.be/) for financial and logistic support. This work was funded by The Fédération Wallonie-Bruxelles (ARC 17/22-087) and by the FRS-FNRS “Brucell-cycle” (PDR T.0060.15). K.P., A.M., and G.P. were supported by a FRIA Ph.D. fellowship. A.R. and N.F. held an Aspirant fellowship from FRS-FNRS. This work was also supported by the French Agence Nationale de Recherche (ANR-JCJC-2011-Castacc) (http://www.agence-nationale-recherche.fr/) and the Region Pas-De-Calais (http://www.nordpasdecalais.fr) CPER to A.F. and E.G.B.

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10.1038/s41467-019-12516-8

Poncin et al. 2019Final published version, 1.28 MB

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Poncin, K., Roba, A., Jimmidi, R., Potemberg, G., Fioravanti, A., Francis, N., Willemart, K., Zeippen, N., Machelart, A., Biondi, E. G., Muraille, E., Vincent, S. P., & De Bolle, X. (2019). Occurrence and repair of alkylating stress in the intracellular pathogen Brucella abortus. Nature Communications, 10(1), 4847. Article 4847. https://doi.org/10.1038/s41467-019-12516-8

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Occurrence and repair of alkylating stress in the intracellular pathogen Brucella abortus

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Biological Security Laboratory Level 3 (BL3)

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Occurrence and repair of alkylating stress in the intracellular pathogen Brucella abortus

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Biological Security Laboratory Level 3 (BL3)

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