Gómez-Garzón Camilo, Payne Shelley M
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, United States.
John Ring LaMontagne Center for Infectious Disease, The University of Texas at Austin, Austin, TX, United States.
Front Microbiol. 2023 Jul 4;14:1219359. doi: 10.3389/fmicb.2023.1219359. eCollection 2023.
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.
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.
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.
Feo是细菌中最广泛存在且保守的亚铁摄取系统，对几种胃肠道病原体的毒力很重要。然而，其机制仍知之甚少。迄今为止，大多数关于Feo系统的研究都集中在γ-变形菌模型上，它们在一个操纵子中具有三个基因（feoA、feoB和feoC）。我们发现人类病原体幽门螺杆菌具有独特的feo基因排列，其中仅存在feoA和feoB且在远距离位点编码。在本研究中，我们研究了这种排列的功能意义。
通过缺失分析和基因表达谱评估单个feo基因的需求和调控。通过系统发育重建推断feo的进化历史，并使用AlphaFold预测FeoA-FeoB相互作用。
Feo功能需要feoA和feoB，并且feoB可能分别受到Fur和NikR对铁和镍的严格调控。此外，我们确定feoA编码在一个操纵子中，该操纵子出现在大多数（但不是全部）螺杆菌的共同祖先中，这导致feoA转录由两个独立的启动子控制。幽门螺杆菌的Feo系统为理解细菌病原体中亚铁转运提供了一个新模型。
