The PAS domain-containing protein HeuR regulates heme uptake in Campylobacter jejuni

Abstract

Campylobacter jejuni is a leading cause of bacterial-derived gastroenteritis. A previous mutant screen demonstrated that the heme uptake system (Chu) is required for full colonization of the chicken gastrointestinal tract. Subsequent work found identified a PAS domain containing regulator, termed HeuR, as required for chicken colonization. Here we confirm that both the heme uptake system and HeuR are required for full chicken gastrointestinal tract colonization, with the heuR mutant being particularly affected during competition with wild-type C. jejuni. Transcriptomic analysis identified the chu genes, and those encoding other iron uptake systems, as likely regulatory targets of HeuR. Purified HeuR specifically bound the chuZA promoter region in electrophoretic mobility shift assays. Consistent with a role for HeuR in chu expression, heuR mutants were unable to efficiently use heme as a source of iron in iron-limiting conditions and, mutants exhibited decreased levels of cell associated iron by mass spectrometry. Finally, we demonstrate that a heuR mutant of C. jejuni is resistant to hydrogen peroxide, and that this resistance correlates to elevated levels of catalase activity.