Biochemistry and evolution of Feo, the major ferrous iron transport system of Vibrio cholerae




Gómez Garzón, Camilo Andrés

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Iron is an essential element for life, and its acquisition entails a challenge for pathogens as they compete with their host and associated microbiota for this element. A major mechanism used by bacterial pathogens to obtain iron from their host is Feo, a widespread prokaryotic system dedicated to the transport of ferrous iron (Fe²⁺), which represents the prevalent form of this metal in the human gut. Despite of the importance of Feo for bacterial pathogens, the mechanism for Feo-mediated iron transport remains poorly understood. In this work, I used the human pathogen Vibrio cholerae as a model organism to study Feo. In V. cholerae, Feo is made up of three components: FeoB, a large transmembrane protein with NTPase activity; and FeoA and FeoC, two small cytoplasmic proteins with unknown function. Current evidence indicate that Feo works as a multimeric complex embedded in the inner membrane and the FeoB NTPase activity is critical for iron transport. In section 1 of Results, I evaluated how different factors affect the enzymatic activity of full-length FeoB in vitro. I found that FeoA, FeoC, Fe²⁺, or K⁺ do not modulate the activity of FeoB. Therefore, FeoB is independent of stimulatory factors, and the roles of FeoA and FeoC might be other than regulation. In section 2, I studied the functional significance specific residues and domains of the Feo proteins for complex formation and iron uptake. According to my results, both the cytoplasmic and transmembrane domains of FeoB are necessary for protein-protein interactions and assembly of the large complex. Also, it may be possible that FeoA and FeoC interact, but this interaction would require the presence of FeoB. Finally, in section 3, I conducted a comprehensive bioinformatic analysis of the Feo protein sequences in bacteria. Complementing the findings from this analysis with in vivo assessments in V. cholerae, I proposed an evolutionary model of the Feo system, focusing on how FeoC might have been lost in several lineages. In summary, this work contributes to the understanding of the Feo system by providing insight into the relationship between its structural organization of and its function.


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