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

Over the last decades, many in vitro studies led to a better understanding of the causes and consequences of alkylating stress on DNA, as well as to the repair mechanisms selected by prokaryotic cells to face it. It has been proposed that pathogenic bacteria have to cope with alkylating stress inside host cells, but this assumption has never been demonstrated. Here, using single cell reporter systems, we show that the class III pathogen Brucella abortus does encounter alkylating stress during the first hours of macrophages infection. Direct repair and base excision repair pathways were identified to be needed by B. abortus to face this stress in vitro and in a mice infection model. In addition, B. abortus relies on distinct strategies than Escherichia coli to control DNA repair gene expression, since we found that some of these genes are under the control of the conserved cell-cycle transcription factor GcrA.