The BER necessities: the repair of DNA damage in human-adapted bacterial pathogens

Key Points Base excision repair (BER) is a highly conserved process that primarily repairs oxidative DNA damage, and human-adapted bacterial pathogens have evolved specialized mechanisms for BER. Mycobacterium tuberculosis displays striking redundancy in the enzymes that prevent incorporation of oxidized guanines into the DNA backbone and excise nucleotides mispaired with this damaged base. By contrast, Helicobacter pylori , which inhabits the gastric mucosa, has a minimal complement of BER enzymes. A network of enzymes recognize and repair DNA damage by BER in Neisseria meningitidis . Expression of the BER enzymes is constitutive in Neisseria meningitidis , which might reflect the high selective pressure of oxidative stress in its habitat in the aerobic upper airways. Further work is required to understand mechanisms of BER in other pathogens and related human commensal species, which should provide insights into whether specialization in BER contributes to colonization and/or human disease. The base excision repair (BER) pathway is the most important mechanism for the repair of oxidative DNA damage, which is frequently encountered by host-adapted bacterial pathogens. Here, van der Veen and Tang review DNA repair in the human pathogens Mycobacterium tuberculosis , Helicobacter pylori and Neisseria meningitidis , highlighting common and distinct mechanisms. During colonization and disease, bacterial pathogens must survive the onslaught of the host immune system. A key component of the innate immune response is the generation of reactive oxygen and nitrogen species by phagocytic cells, which target and disrupt pathogen molecules, particularly DNA, and the base excision repair (BER) pathway is the most important mechanism for the repair of such oxidative DNA damage. In this Review, we discuss how the human-specific pathogens Mycobacterium tuberculosis , Helicobacter pylori and Neisseria meningitidis have evolved specialized mechanisms of DNA repair, particularly their BER pathways, compared with model organisms such as Escherichia coli . This specialization in DNA repair is likely to reflect the distinct niches occupied by these important human pathogens in the host.