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.
Highlights
It is assumed that intracellular pathogenic bacteria have to cope with DNA alkylating stress within host cells
We found that many intracellular bacteria, including obligate pathogens such as Chlamydia pneumoniae and Coxiella burnettii, have genes homologous to some of known DNA repair genes (Fig. 1)
A mutated version of the reporter system was used as a negative control, in which a C38A mutation was introduced in Ada to prevent the protein from capturing meP3ester groups
Summary
It is assumed that intracellular pathogenic bacteria have to cope with DNA alkylating stress within host cells. 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. Three main endogenous sources of alkylating agents are reported in living organisms: (1) the ubiquitous methyl-donor Sadenosylmethionine (SAM)[5], (2) lipid peroxidation-derived alkylating agents[6], and (3) N-nitroso compounds resulting from the nitrosation of metabolites and being either direct alkylating agents or requiring metabolic activation[7,8,9]. In E. coli, the majority of the spontaneous mutations resulting from alkylating stress was found to be generated via the endogenous formation of N-nitroso compounds[7,14]
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