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      Staphylococcus aureus host interactions and adaptation

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          Abstract

          Invasive Staphylococcus aureus infections are common, causing high mortality, compounded by the propensity of the bacterium to develop drug resistance. S. aureus is an excellent case study of the potential for a bacterium to be commensal, colonizing, latent or disease-causing; these states defined by the interplay between S. aureus and host. This interplay is multidimensional and evolving, exemplified by the spread of S. aureus between humans and other animal reservoirs and the lack of success in vaccine development. In this Review, we examine recent advances in understanding the S. aureus–host interactions that lead to infections. We revisit the primary role of neutrophils in controlling infection, summarizing the discovery of new immune evasion molecules and the discovery of new functions ascribed to well-known virulence factors. We explore the intriguing intersection of bacterial and host metabolism, where crosstalk in both directions can influence immune responses and infection outcomes. This Review also assesses the surprising genomic plasticity of S. aureus, its dualism as a multi-mammalian species commensal and opportunistic pathogen and our developing understanding of the roles of other bacteria in shaping S. aureus colonization.

          Abstract

          In this Review, Howden and co-workers examine and integrate recent key advances in understanding the mechanisms that Staphylococcus aureus uses to cause infections.

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          Most cited references177

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          Myeloid-derived suppressor cells as regulators of the immune system.

          Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that expand during cancer, inflammation and infection, and that have a remarkable ability to suppress T-cell responses. These cells constitute a unique component of the immune system that regulates immune responses in healthy individuals and in the context of various diseases. In this Review, we discuss the origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit.
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            Succinate is an inflammatory signal that induces IL-1β through HIF-1α.

            Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation.
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              A guide to immunometabolism for immunologists.

              In recent years a substantial number of findings have been made in the area of immunometabolism, by which we mean the changes in intracellular metabolic pathways in immune cells that alter their function. Here, we provide a brief refresher course on six of the major metabolic pathways involved (specifically, glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, fatty acid oxidation, fatty acid synthesis and amino acid metabolism), giving specific examples of how precise changes in the metabolites of these pathways shape the immune cell response. What is emerging is a complex interplay between metabolic reprogramming and immunity, which is providing an extra dimension to our understanding of the immune system in health and disease.
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                Author and article information

                Contributors
                bhowden@unimelb.edu.au
                Journal
                Nat Rev Microbiol
                Nat Rev Microbiol
                Nature Reviews. Microbiology
                Nature Publishing Group UK (London )
                1740-1526
                1740-1534
                27 January 2023
                : 1-16
                Affiliations
                [1 ]GRID grid.1008.9, ISNI 0000 0001 2179 088X, Centre for Pathogen Genomics, , The University of Melbourne, ; Melbourne, Victoria Australia
                [2 ]GRID grid.1008.9, ISNI 0000 0001 2179 088X, Department of Microbiology and Immunology, , The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, ; Melbourne, Victoria Australia
                [3 ]GRID grid.410678.c, ISNI 0000 0000 9374 3516, Department of Infectious Diseases, , Austin Health, ; Heidelberg, Victoria Australia
                [4 ]GRID grid.416153.4, ISNI 0000 0004 0624 1200, Microbiology Department, , Royal Melbourne Hospital, ; Melbourne, Victoria Australia
                [5 ]GRID grid.416153.4, ISNI 0000 0004 0624 1200, Victorian Infectious Diseases Service, , Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, ; Melbourne, Victoria Australia
                [6 ]GRID grid.21729.3f, ISNI 0000000419368729, Department of Paediatrics, , Columbia University, ; New York, NY USA
                [7 ]GRID grid.419789.a, ISNI 0000 0000 9295 3933, Department of Infectious Diseases, , Monash Health, ; Clayton, Victoria Australia
                Author information
                http://orcid.org/0000-0003-0237-1473
                http://orcid.org/0000-0001-5366-1943
                http://orcid.org/0000-0002-9318-9572
                http://orcid.org/0000-0002-0557-0518
                http://orcid.org/0000-0001-9324-8678
                http://orcid.org/0000-0001-5751-8503
                http://orcid.org/0000-0001-8032-2154
                http://orcid.org/0000-0001-6982-8074
                http://orcid.org/0000-0003-0150-123X
                Article
                852
                10.1038/s41579-023-00852-y
                9882747
                36707725
                7bcd8be2-1a97-4ed8-ac95-f00880008f7d
                © Springer Nature Limited 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 4 January 2023
                Categories
                Review Article

                bacteriology,bacterial infection
                bacteriology, bacterial infection

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