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PLoS Pathog. 2015 Dec 4;11(12):e1005317. doi: 10.1371/journal.ppat.1005317. eCollection 2015 Dec.

The Extraintestinal Pathogenic Escherichia coli Factor RqlI Constrains the Genotoxic Effects of the RecQ-Like Helicase RqlH.

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University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, Utah, United States of America.


Extraintestinal pathogenic Escherichia coli colonize the human gut and can spread to other body sites to induce diseases such as urinary tract infections, sepsis, and meningitis. A complete understanding of the infection process is hindered by both the inherent genetic diversity of E. coli and the large number of unstudied genes. Here, we focus on the uncharacterized gene rqlI, which our lab recently uncovered in a Tn-seq screen for bacterial genes required within a zebrafish model of infection. We demonstrate that the ΔrqlI mutant experiences a growth defect and increased DNA stress in low oxygen conditions. In a genetic screen for suppressor mutations in the Δrql strain, we found that the shortcomings of the Δrql mutant are attributable to the activity of RqlH, which is known in other bacteria to be a helicase of the RecQ family that contains a phosphoribosyltransferase (PRTase) domain. Disruption of rqlH rescues the ΔrqlI strain in both in vivo and in vitro assays, while the expression of RqlH alone activates the SOS response coincident with bacterial filamentation, heightened sensitivity to DNA damage, and an increased mutation rate. The analysis of truncation mutants indicates that, in the absence of RqlI, RqlH toxicity is due to its PRTase domain. Complementary studies demonstrate that the toxicity of RqlH is modulated in a context-dependent fashion by overlapping domains within RqlI. This regulation is seemingly direct, given that the two proteins physically interact and form an operon. Interestingly, RqlH and RqlI orthologs are encoded by a diverse group of bacteria, but in many of these microbes, and especially in Gram-positive organisms, rqlH is found in the absence of rqlI. In total, this work shows that RqlH and RqlI can act in a strain-specific fashion akin to a toxin-antitoxin system in which toxicity is mediated by an atypical helicase-associated PRTase domain.

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