More Like this

1. Manganese transporters regulate the resumption of replication in hydrogen peroxide-stressed Escherichia coli

   https://doi.org/10.1007/s10534-023-00523-8  

   Wang, Natalie E.; Courcelle, Eleanor J.; Coltman, Samantha M.; Spolek, Raymond L.; Courcelle, Justin; Courcelle, Charmain T. (July 2023, BioMetals)

   Following hydrogen peroxide treatment, ferrous iron (Fe2+) is oxidized to its ferric form (Fe3+), stripping it from and inactivating iron-containing proteins. Many mononuclear iron enzymes can be remetallated by manganese to restore function, while other enzymes specifically utilize manganese as a cofactor, having redundant activities that compensate for iron-depleted counterparts. DNA replication relies on one or more iron-dependent protein(s) as synthesis abates in the presence of hydrogen peroxide and requires manganese in the medium to resume. Here, we show that manganese transporters regulate the ability to resume replication following oxidative challenge in Escherichia coli. The absence of the primary manganese importer, MntH, impairs the ability to resume replication; whereas deleting the manganese exporter, MntP, or transporter regulator, MntR, dramatically increases the rate of recovery. Unregulated manganese import promoted recovery even in the absence of Fur, which maintains iron homeostasis. Similarly, replication was not restored in oxyR mutants, which cannot upregulate manganese import following hydrogen peroxide stress. Taken together, the results define a central role for manganese transport in restoring replication following oxidative stress. 

   more » « less
2. Disentangling the Evolutionary History of Feo, the Major Ferrous Iron Transport System in Bacteria

   https://doi.org/10.1128/mbio.03512-21  

   Gómez-Garzón, Camilo; Barrick, Jeffrey E.; Payne, Shelley M. (February 2022, mBio)

   Ruby, Edward G. (Ed.)

   ABSTRACT Iron acquisition is essential for almost all living organisms. In certain environments, ferrous iron is the most prevalent form of this element. Feo is the most widespread system for ferrous iron uptake in bacteria and is critical for virulence in some species. The canonical architecture of Feo consists of a large transmembrane nucleoside triphosphatase (NTPase) protein, FeoB, and two accessory cytoplasmic proteins, FeoA and FeoC. The role of the latter components and the mechanism by which Feo orchestrates iron transport are unclear. In this study, we conducted a comparative analysis of Feo protein sequences to gain insight into the evolutionary history of this transporter. We identified instances of how horizontal gene transfer contributed to the evolution of Feo. Also, we found that FeoC, while absent in most lineages, is largely present in the Gammaproteobacteria group, although its sequence is poorly conserved. We propose that FeoC, which may couple FeoB NTPase activity with pore opening, was an ancestral element that has been dispensed with through mutations in FeoA and FeoB in some lineages. We provide experimental evidence supporting this hypothesis by isolating and characterizing FeoC-independent mutants of the Vibrio cholerae Feo system. Also, we confirmed that the closely related species Shewanella oneidensis does not require FeoC; thus, Vibrio FeoC sequences may resemble transitional forms on an evolutionary pathway toward FeoC-independent transporters. Finally, by combining data from our bioinformatic analyses with this experimental evidence, we propose an evolutionary model for the Feo system in bacteria. IMPORTANCE Feo, a ferrous iron transport system composed of three proteins (FeoA, -B, and -C), is the most prevalent bacterial iron transporter. It plays an important role in iron acquisition in low-oxygen environments and some host-pathogen interactions. The large transmembrane protein FeoB provides the channel for the transport of iron into the bacterial cell, but the functions of the two small, required accessory proteins FeoA and FeoC are not well understood. Analysis of the evolution of this transporter shows that FeoC is poorly conserved and has been lost from many bacterial lineages. Experimental evidence indicates that FeoC may have different functions in different species that retain this protein, and the loss of FeoC is promoted by mutations in FeoA or by the fusion of FeoA and FeoB. 

   more » « less
3. Iron cycling and isotopic fractionation in a ferruginous, seasonally ice-covered lake

   https://doi.org/10.1016/j.gca.2024.07.037  

   Heard, Andy W; Ostrander, Chadlin M; Swanner, Elizabeth D; Rico, Kathryn; Nielsen, Sune G (October 2024, Geochimica et Cosmochimica Acta)

   Ferruginous conditions, defined by anoxia and abundant dissolved ferrous iron (Fe2+aq), dominated the Precambrian oceans but are essentially non-existent in a modern, oxygenated world. Ferruginous meromictic lakes represent natural laboratories to ground truth our understanding of the stable Fe isotope proxy, which has been used extensively in interpreting the origins of Fe-rich sedimentary rocks like iron formations (IFs) and the interactions of early life with high-Fe2+aq conditions. Here we report comprehensive geochemical and Fe isotopic analyses of samples collected in May and August 2022, and March 2023, from Deming Lake, Minnesota, a ferruginous meromictic lake that undergoes surface freezing in winter and never becomes euxinic. Through chemical and Fe isotopic analyses of different putative Fe sources to Deming Lake; including eolian input trapped in winter ice cover, nearby bogs, and regional groundwaters sampled at surface springs; we find that a groundwater source provides the best chemical and Fe isotopic match for Deming Lake and can support Fe2+aq-rich waters at depth that maintain a permanent chemocline at ~12 m. The ice-free Deming Lake water column can be split into three layers dominated by distinct Fe cycling regimes. Layer (I) extends from the lake surface to the base of the oxycline at ~6 m, and its Fe cycling is dominated by isotopically light Fe uptake into biomass, likely from stabilized dissolved Fe3+, with variable eolian lithogenic influences. Layer (II) extends between the oxycline and the chemocline at ~12 m and is dominated by partial Fe2+aq oxidation on approach to the oxycline, with the formation of variably isotopically heavy Fe3+-bearing particles. Layer (III) underlies the chemocline and is defined by Fe2+ phosphate (vivianite) and carbonate saturation and precipitation under anoxic, Fe2+aq-rich conditions with little Fe isotopic fractionation. The ice-covered winter water column features more homogenous Fe chemistry above the chemocline, which we attribute to seasonal homogenization of Layers (I) and (II), with suppressed ferric particle formation. Authigenic Fe minerals with non-crustal (light) Fe isotopic compositions only appreciably accumulate in sediments in Deming Lake underlying the chemocline. All sediments deposited above 12 m appear crustal in their Fe isotopic, Mn/Fe, and Fe/Al ratios, likely revealing efficient reductive dissolution of Fe3+-bearing lake precipitates and remineralization of Fe-bearing biomass. We find limited fractionation of Fe isotopes in the ice-covered water column and suggest this provides evidence that substantial delivery of oxidants is required to generate highly fractionated Fe isotopic compositions in Sturtian Snowball era IFs. By comparing Fe isotopic and Mn/Fe fractionation trends in the different Deming Lake layers, we also suggest that correlations between these two parameters in giant early Paleoproterozoic IFs requires the simultaneous deposition of multiple authigenic phases on the ancient seafloor. Finally, high-precision triple Fe isotopic analyses of dissolved Fe impacted by extensive oxidation near the Deming Lake oxycline reveal that the slope of the mass fractionation law for natural, O2-mediated Fe2+aq oxidation is identical to those previously defined for both UV photo-oxidation, and for an array of highly fractionated Paleoproterozoic IFs. 

   more » « less
4. Dynamic Autoregressive Tensor Factorization for Pattern Discovery of Spatiotemporal Systems

   https://doi.org/10.1109/TPAMI.2025.3576719  

   Chen, Xinyu; Zhuang, Dingyi; Cai, HanQin; Wang, Shenhao; Zhao, Jinhua (June 2025, IEEE Transactions on Pattern Analysis and Machine Intelligence)

   Spatiotemporal systems are ubiquitous in a large number of scientific areas, representing underlying knowledge and patterns in the data. Here, a fundamental question usually arises as how to understand and characterize these spatiotemporal systems with a certain data-driven machine learning framework. In this work, we introduce an unsupervised pattern discovery framework, namely, dynamic autoregressive tensor factorization. Our framework is essentially built on the fact that the spatiotemporal systems can be well described by the time-varying autoregression on multivariate or even multidimensional data. In the modeling process, tensor factorization is seamlessly integrated into the time-varying autoregression for discovering spatial and temporal modes/patterns from the spatiotemporal systems in which the spatial factor matrix is assumed to be orthogonal. To evaluate the framework, we apply it to several real-world spatiotemporal datasets, including fluid flow dynamics, international import/export merchandise trade, and urban human mobility. On the international trade dataset with dimensions {country/region, product type, year}, our framework can produce interpretable import/export patterns of countries/regions, while the low-dimensional product patterns are also important for classifying import/export merchandise and understanding systematical differences between import and export. On the ridesharing mobility dataset with dimensions {origin, destination, time}, our framework is helpful for identifying the shift of spatial patterns of urban human mobility that changed between 2019 and 2022. Empirical experiments demonstrate that our framework can discover interpretable and meaningful patterns from the spatiotemporal systems that are both time-varying and multidimensional. 

   more » « less
5. Iron Oxidation by a Fused Cytochrome-Porin Common to Diverse Iron-Oxidizing Bacteria

   https://doi.org/10.1128/mBio.01074-21  

   Keffer, Jessica L.; McAllister, Sean M.; Garber, Arkadiy I.; Hallahan, Beverly J.; Sutherland, Molly C.; Rozovsky, Sharon; Chan, Clara S. (January 2021, mBio)

   Komeili, Arash (Ed.)

   Iron (Fe) oxidation is one of Earth’s major biogeochemical processes, key to weathering, soil formation, water quality, and corrosion. However, our understanding of microbial contribution is limited by incomplete knowledge of microbial iron oxidation mechanisms, particularly in neutrophilic iron oxidizers. The genomes of many diverse iron oxidizers encode a homolog to an outer membrane cytochrome (Cyc2) shown to oxidize iron in two acidophiles. Phylogenetic analyses show Cyc2 sequences from neutrophiles cluster together, suggesting a common function, though this function has not been verified in these organisms. Therefore, we investigated the iron oxidase function of heterologously expressed Cyc2 from a neutrophilic iron oxidizer Mariprofundus ferrooxydans PV-1. Cyc2 PV-1 is capable of oxidizing iron, and its redox potential is 208 ± 20 mV, consistent with the ability to accept electrons from Fe2+ at neutral pH. These results support the hypothesis that Cyc2 functions as an iron oxidase in neutrophilic iron-oxidizing organisms. The results of sequence analysis and modeling reveal that the entire Cyc2 family shares a unique fused cytochrome-porin structure, with a defining consensus motif in the cytochrome region. On the basis of results from structural analyses, we predict that the monoheme cytochrome Cyc2 specifically oxidizes dissolved Fe2+, in contrast to multiheme iron oxidases, which may oxidize solid Fe(II). With our results, there is now functional validation for diverse representatives of Cyc2 sequences. We present a comprehensive Cyc2 phylogenetic tree and offer a roadmap for identifying cyc2/Cyc2 homologs and interpreting their function. The occurrence of cyc2 in many genomes beyond known iron oxidizers presents the possibility that microbial iron oxidation may be a widespread metabolism. IMPORTANCE Iron is practically ubiquitous across Earth’s environments, central to both life and geochemical processes, which depend heavily on the redox state of iron. Although iron oxidation, or “rusting,” can occur abiotically at near-neutral pH, we find neutrophilic iron-oxidizing bacteria (FeOB) are widespread, including in aquifers, sediments, hydrothermal vents, pipes, and water treatment systems. FeOB produce highly reactive Fe(III) oxyhydroxides that bind a variety of nutrients and toxins; thus, these microbes are likely a controlling force in iron and other biogeochemical cycles. There has been mounting evidence that Cyc2 functions as an iron oxidase in neutrophiles, but definitive proof of its function has long eluded us. This work provides conclusive biochemical evidence of iron oxidation by Cyc2 from neutrophiles. Cyc2 is common to a wide variety of iron oxidizers, including acidophilic and phototrophic iron oxidizers, suggesting that this fused cytochrome-porin structure is especially well adapted for iron oxidation. 

   more » « less