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      Resisting death by metal: metabolism and Cu/Zn homeostasis in bacteria

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          Abstract

          Metal ions such as zinc and copper play important roles in host–microbe interactions and their availability can drastically affect the survival of pathogenic bacteria in a host niche. Mechanisms of metal homeostasis protect bacteria from starvation, or intoxication, defined as when metals are limiting, or in excess, respectively. In this mini-review, we summarise current knowledge on the mechanisms of resistance to metal stress in bacteria, focussing specifically on the homeostasis of cellular copper and zinc. This includes a summary of the factors that subvert metal stress in bacteria, which are independent of metal efflux systems, and commentary on the role of small molecules and metabolic systems as important mediators of metal resistance.

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          ChEBI in 2016: Improved services and an expanding collection of metabolites

          Janna Hastings, Gareth S. Owen, Adriano Dekker … (2016)
          ChEBI is a database and ontology containing information about chemical entities of biological interest. It currently includes over 46 000 entries, each of which is classified within the ontology and assigned multiple annotations including (where relevant) a chemical structure, database cross-references, synonyms and literature citations. All content is freely available and can be accessed online at http://www.ebi.ac.uk/chebi. In this update paper, we describe recent improvements and additions to the ChEBI offering. We have substantially extended our collection of endogenous metabolites for several organisms including human, mouse, Escherichia coli and yeast. Our front-end has also been reworked and updated, improving the user experience, removing our dependency on Java applets in favour of embedded JavaScript components and moving from a monthly release update to a ‘live’ website. Programmatic access has been improved by the introduction of a library, libChEBI, in Java, Python and Matlab. Furthermore, we have added two new tools, namely an analysis tool, BiNChE, and a query tool for the ontology, OntoQuery.
          Article 0 comments Cited 416 times – based on 0 reviews     Review now
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            Metal ions in biological catalysis: from enzyme databases to general principles.

            Claudia Andreini, Ivano Bertini, Gabriele Cavallaro … (2008)
            We analysed the roles and distribution of metal ions in enzymatic catalysis using available public databases and our new resource Metal-MACiE (http://www.ebi.ac.uk/thornton-srv/databases/Metal_MACiE/home.html). In Metal-MACiE, a database of metal-based reaction mechanisms, 116 entries covering 21% of the metal-dependent enzymes and 70% of the types of enzyme-catalysed chemical transformations are annotated according to metal function. We used Metal-MACiE to assess the functions performed by metals in biological catalysis and the relative frequencies of different metals in different roles, which can be related to their individual chemical properties and availability in the environment. The overall picture emerging from the overview of Metal-MACiE is that redox-inert metal ions are used in enzymes to stabilize negative charges and to activate substrates by virtue of their Lewis acid properties, whereas redox-active metal ions can be used both as Lewis acids and as redox centres. Magnesium and zinc are by far the most common ions of the first type, while calcium is relatively less used. Magnesium, however, is most often bound to phosphate groups of substrates and interacts with the enzyme only transiently, whereas the other metals are stably bound to the enzyme. The most common metal of the second type is iron, which is prevalent in the catalysis of redox reactions, followed by manganese, cobalt, molybdenum, copper and nickel. The control of the reactivity of redox-active metal ions may involve their association with organic cofactors to form stable units. This occurs sometimes for iron and nickel, and quite often for cobalt and molybdenum.
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              Nutritional immunity: transition metals at the pathogen-host interface.

              M. Hood, Eric P. Skaar (2012)
              Transition metals occupy an essential niche in biological systems. Their electrostatic properties stabilize substrates or reaction intermediates in the active sites of enzymes, and their heightened reactivity is harnessed for catalysis. However, this heightened activity also renders transition metals toxic at high concentrations. Bacteria, like all living organisms, must regulate their intracellular levels of these elements to satisfy their physiological needs while avoiding harm. It is therefore not surprising that the host capitalizes on both the essentiality and toxicity of transition metals to defend against bacterial invaders. This Review discusses established and emerging paradigms in nutrient metal homeostasis at the pathogen-host interface.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Emerg Top Life Sci
                Journal ID (iso-abbrev): Emerg Top Life Sci
                Journal ID (publisher-id): ETLS
                Title: Emerging Topics in Life Sciences
                Publisher: Portland Press Ltd.
                ISSN (Print): 2397-8554
                ISSN (Electronic): 2397-8562
                Publication date Collection: 22 February 2024
                Publication date (Electronic): 16 February 2024
                Volume: 8
                Issue: 1
                Pages: 45-56
                Affiliations
                [1 ]School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, U.K.
                [2 ]School of Pharmacy and Medical Sciences, and Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, Gold Coast, QLD 4222, Australia
                Author notes
                Correspondence: Matthew J. Sullivan ( matthew.sullivan@ 123456uea.ac.uk )
                Author information
                https://orcid.org/0000-0003-2276-3132
                https://orcid.org/0000-0001-8347-2043
                https://orcid.org/0000-0002-9638-8091
                Article
                Publisher ID: ETLS-8-45
                DOI: 10.1042/ETLS20230115
                PMC ID: 10903455
                PubMed ID: 38362914
                SO-VID: 7d0f52d2-15d6-43eb-a19f-1e4847c33f7e
                Copyright © © 2024 The Author(s)
                License:

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and the Royal Society of Biology and distributed under the Creative Commons Attribution License 4.0 (CC BY). Open access for this article was enabled by the participation of University of East Anglia in an all-inclusive Read & Publish agreement with Portland Press and the Biochemical Society under a transformative agreement with JISC.

                History
                Date received : 16 October 2023
                Date revision received : 31 January 2024
                Date accepted : 4 February 2024
                Categories
                Subject: Microbiology
                Subject: Molecular Bases of Health & Disease
                Subject: Host-Microbe Interactions
                Subject: Review Articles

                Keywords: copper,homeostasis,metabolism,metal,small molecules,zinc
                Data availability:
                Keywords: copper, homeostasis, metabolism, metal, small molecules, zinc

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