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ORIGINAL RESEARCH article
Front. Chem.
Sec. Chemical Biology
Volume 13 - 2025 | doi: 10.3389/fchem.2025.1562189
This article is part of the Research Topic Exploration of the Role of Heme Proteins in Biology with Experimental and Computational Methods View all 6 articles
Heme and iron limitation in a GI-tract foundation species leads to a reshuffling of the metalloproteome and a shift toward manganese usage
Provisionally accepted- Montana State University, Bozeman, United States
The metal-binding complement of the cellular proteome (the metalloproteome) depends on metal availability in the cellular environment and drives cellular metabolism.Bacteroides thetaiotaomicron (B. theta) is a foundational species in the anaerobic gut microbiome and a heme auxotroph, though little is known about why it requires heme.We hypothesized that B. theta would overproduce heme-binding proteins in response to limitations in non-heme iron, and reciprocally, activate non-heme iron pathways when heme was growth limiting. Here we showed that heme and/or non-heme iron scarcity triggers a more holistic reorganization of its metallome and metalloproteome. Under non-heme iron limitation induced by an Fe(II)-specific chelator, manganese supplementation restored growth, suggesting manganese can partly compensate for non-heme iron. Metalloproteomic analyses using tandem HPLC-ICP-MS revealed significant changes in the distribution of zinc, manganese, and iron in response to varying iron or heme availability. These findings highlight the interplay between heme/non-heme iron and the metallome in bacterial growth regulation, and they underscore a role for manganese under iron scarcity.
Keywords: Bacteroides thetaiotaomicron, Heme, Hemeprotein, Iron, Manganese, metalloproteome, microbiome, Mass Spectrometry
Received: 17 Jan 2025; Accepted: 17 Mar 2025.
Copyright: © 2025 DuBois, Rodrigues Da Silva, Larson and Bothner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jennifer L DuBois, Montana State University, Bozeman, United States
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