Preprint Article Version 1 This version is not peer-reviewed

Metalloproteomics Reveals Multi-Level Stress Response in Escherichia Coli When Exposed to Arsenite

Version 1 : Received: 8 August 2024 / Approved: 9 August 2024 / Online: 9 August 2024 (08:30:15 CEST)

How to cite: Larson, J.; Sather, B.; Wang, L.; Westrum, J.; Tokmina-Lukaszewska, M.; Pauley, J.; Copié, V.; McDermott, T. R.; Bothner, B. Metalloproteomics Reveals Multi-Level Stress Response in Escherichia Coli When Exposed to Arsenite. Preprints 2024, 2024080690. https://doi.org/10.20944/preprints202408.0690.v1 Larson, J.; Sather, B.; Wang, L.; Westrum, J.; Tokmina-Lukaszewska, M.; Pauley, J.; Copié, V.; McDermott, T. R.; Bothner, B. Metalloproteomics Reveals Multi-Level Stress Response in Escherichia Coli When Exposed to Arsenite. Preprints 2024, 2024080690. https://doi.org/10.20944/preprints202408.0690.v1

Abstract

The arsRBC operon encodes a 3-protein arsenic resistance system. ArsR regulates the transcription of the operon, while ArsB and ArsC are involved in exporting trivalent arsenic and reducing pentavalent arsenic respectively. Previous research in Agrobacterium tumefaciens 5A demonstrated ArsR has regulatory control over a wide range of metal related proteins and metabolic pathways. We hypothesized that ArsR has broad regulatory control in other Gram-negative bacteria and set out to test this. Here, we use differential proteomics to investigate changes caused by the presence of the arsR gene in human microbiome-relevant Escherichia coli during arsenite (AsIII) exposure. We show that ArsR has broad-ranging impacts such as the expression of TCA cycle enzymes during AsIII stress. Additionally, we found that the Isc [Fe-S] cluster and molybdenum cofactor assembly proteins are upregulated regardless of the presence of ArsR under these same conditions. An important finding from this differential proteomics analysis was the identification of response mechanisms that were strain, ArsR, and arsenic specific, providing new clarity to this complex regulon. Given the widespread occurrence of the arsRBC operon, these findings should have broad applicability across microbial genera, including sensitive environments such as the human gastrointestinal tract.

Keywords

arsenic; bacteria; metalloproteome; metal; TCA cycle; iron-sulfur cluster; molybdenum cofactor

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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