Xer Recombinase and Genome Integrity in Helicobacter pylori, a Pathogen without Topoisomerase IV

Aleksandra Debowski, C. Carnoy, Phebe Verbrugghe, H.O. Nilsson, J.C. Gauntlett, Alma Fulurija, T. Camilleri, D.E. Berg, Barry Marshall, Mohammed Benghezal

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Abstract

In the model organism E. coli, recombination mediated by the related XerC and XerD recombinases complexed with the FtsK translocase at specialized dif sites, resolves dimeric chromosomes into free monomers to allow efficient chromosome segregation at cell division. Computational genome analysis of Helicobacter pylori, a slow growing gastric pathogen, identified just one chromosomal xer gene (xerH) and its cognate dif site (difH). Here we show that recombination between directly repeated difH sites requires XerH, FtsK but not XerT, the TnPZ transposon associated recombinase. xerH inactivation was not lethal, but resulted in increased DNA per cell, suggesting defective chromosome segregation. The xerH mutant also failed to colonize mice, and was more susceptible to UV and ciprofloxacin, which induce DNA breakage, and thereby recombination and chromosome dimer formation. xerH inactivation and overexpression each led to a DNA segregation defect, suggesting a role for Xer recombination in regulation of replication. In addition to chromosome dimer resolution and based on the absence of genes for topoisomerase IV (parC, parE) in H. pylori, we speculate that XerH may contribute to chromosome decatenation, although possible involvement of H. pylori's DNA gyrase and topoisomerase III homologue are also considered. Further analyses of this system should contribute to general understanding of and possibly therapy development for H. pylori, which causes peptic ulcers and gastric cancer; for the closely related, diarrheagenic Campylobacter species; and for unrelated slow growing pathogens that lack topoisomerase IV, such as Mycobacterium tuberculosis.
Original languageEnglish
Pages (from-to)15pp
JournalPLoS One
Volume7
Issue number4
DOIs
Publication statusPublished - 2012

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    Debowski, A., Carnoy, C., Verbrugghe, P., Nilsson, H. O., Gauntlett, J. C., Fulurija, A., Camilleri, T., Berg, D. E., Marshall, B., & Benghezal, M. (2012). Xer Recombinase and Genome Integrity in Helicobacter pylori, a Pathogen without Topoisomerase IV. PLoS One, 7(4), 15pp. https://doi.org/10.1371/journal.pone.0033310