Divide and conquer: genetics, mechanism, and evolution of the ferrous iron transporter Feo in .

INTRODUCTION

Feo is the most widespread and conserved system for ferrous iron uptake in bacteria, and it is important for virulence in several gastrointestinal pathogens. However, its mechanism remains poorly understood. Hitherto, most studies regarding the Feo system were focused on Gammaproteobacterial models, which possess three (, , and ) clustered in an operon. We found that the human pathogen possesses a unique arrangement of the feo genes, in which only and are present and encoded in distant loci. In this study, we examined the functional significance of this arrangement.

METHODS

Requirement and regulation of the individual feo genes were assessed through assays and gene expression profiling. The evolutionary history of feo was inferred via phylogenetic reconstruction, and AlphaFold was used for predicting the FeoA-FeoB interaction.

RESULTS AND DISCUSSION

Both and are required for Feo function, and feoB is likely subjected to tight regulation in response to iron and nickel by Fur and NikR, respectively. Also, we established that is encoded in an operon that emerged in the common ancestor of most, but not all, helicobacters, and this resulted in transcription being controlled by two independent promoters. The Feo system offers a new model to understand ferrous iron transport in bacterial pathogens.