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We applied multi-omics approaches (transcriptomics, proteomics and metabolomics) to study the effect of iron starvation on the Gram-positive human pathogen to elucidate global changes in the bacterium in a condition similar to what can be found in the host during an infectious episode. We treated the reference strain TIGR4 with the iron chelator deferoxamine mesylate. DNA microarrays revealed changes in the expression of operons involved in multiple biological processes, with a prevalence of genes coding for ion binding proteins. We also studied the changes in protein abundance by 2-DE followed by MALDI-TOF/TOF analysis of total cell extracts and secretome fractions. The main proteomic changes were found in proteins related to the primary and amino sugar metabolism, especially in enzymes with divalent cations as cofactors. Finally, the metabolomic analysis of intracellular metabolites showed altered levels of amino sugars involved in the cell wall peptidoglycan metabolism. This work shows the utility of multi-perspective studies that can provide complementary results for the comprehension of how a given condition can influence global physiological changes in microorganisms.
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http://dx.doi.org/10.7717/peerj.4966 | DOI Listing |
J Extracell Vesicles
September 2025
State Key Laboratory of Metabolism and Regulation in Complex Organisms, Hubei Provincial Research Center for Basic Biological Sciences, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, RNA Institute, Wuhan University, Wuhan, China.
Tumour progression depends on the bidirectional interactions between cancer and stroma in the heterogeneous tumour microenvironment (TME) partially through extracellular vesicles (EVs). However, the secretary mechanism and biological effect of cancer cell derived EVs on tumour survival under starvation is poorly defined. Here, we identify cancer cells selectively secrete miR-33a with the assistance of aconitase 1 (ACO1), an iron-responsive RNA binding protein, under glucose starvation and lower iron level, which affiliates the binding capability of miR-33a and ACO1.
View Article and Find Full Text PDFbioRxiv
August 2025
Biosciences Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom.
Iron is an essential element that can be growth-limiting in microbial communities, particularly those present within host organisms. To acquire iron, many bacteria secrete siderophores, secondary metabolites that chelate ferric iron. These iron chelates can be transported back into the cell via TonB-dependent transporters in the outer membrane, followed by intracellular liberation of the iron.
View Article and Find Full Text PDFbioRxiv
August 2025
Mcketta Department of Chemical Engineering, University of Texas at Austin, Austin TX.
Recent studies have demonstrated the importance of dynamic heterochromatin-like regions in bacterial gene regulation, particularly for adaptation to changing environments. Here, we have measured the dynamic regulatory protein-DNA landscape of the tuberculosis vaccine strain, BCG Pasteur, under the pathogenically-relevant condition of iron starvation. Our results capture for the first time the overall protein occupancy landscape of the genome of BCG, identifying extended protein occupancy domains likely composed of diverse sets of nucleoid-associated proteins and transcription factors.
View Article and Find Full Text PDFMicrobiol Spectr
September 2025
Department of Biological Sciences, Molecular and Computational Biology Section, University of Southern California, Los Angeles, California, USA.
expresses three ferritins that store acquired iron by oxidizing soluble Fe(II) to insoluble Fe(III), which can accumulate and later be utilized in cellular processes. Although bacterioferritin (Bfr) and ferritin (FtnA) sequester more Fe(III) atoms per multimeric complex, the abundance of the DNA-binding protein from starved cells (Dps), coupled with its preference for hydrogen peroxide as an oxidant in its ferroxidase activity, makes it a fundamental component in iron homeostasis and long-term stationary phase (LTSP) survival. To investigate the temporal role and mechanisms of action of Dps in parallel with the other ferritins, growth yield, survival, competitive fitness, and siderophore assays were performed under different conditions of iron availability.
View Article and Find Full Text PDFNucleic Acids Res
August 2025
Institute of Molecular Biology, Biocenter, Medical University Innsbruck, 6020 Innsbruck, Austria.
Accurate sensing of cellular iron levels is vital, as this metal is essential but toxic in excess. The iron-sensing transcription factor HapX is crucial for virulence of Aspergillus fumigatus, the predominant human mold pathogen. Its absence impairs growth under iron limitation and excess, but not under moderate iron availability, suggesting that HapX switches between three states to adapt to varying iron availability.
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