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      A Pseudomonas T6SS effector recruits PQS-containing outer membrane vesicles for iron acquisition

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          Abstract

          Iron sequestration by host proteins contributes to the defence against bacterial pathogens, which need iron for their metabolism and virulence. A Pseudomonas aeruginosa mutant lacking all three known iron acquisition systems retains the ability to grow in media containing iron chelators, suggesting the presence of additional pathways involved in iron uptake. Here we screen P. aeruginosa mutants defective in growth in iron-depleted media and find that gene PA2374, proximal to the type VI secretion system H3 (H3-T6SS), functions synergistically with known iron acquisition systems. PA2374 (which we have renamed TseF) appears to be secreted by H3-T6SS and is incorporated into outer membrane vesicles (OMVs) by directly interacting with the iron-binding Pseudomonas quinolone signal (PQS), a cell–cell signalling compound. TseF facilitates the delivery of OMV-associated iron to bacterial cells by engaging the Fe(III)-pyochelin receptor FptA and the porin OprF. Our results reveal links between type VI secretion, cell–cell signalling and classic siderophore receptors for iron acquisition in P. aeruginosa.

          Abstract

          Pathogens require iron for their metabolism and virulence. Here the authors identify an iron acquisition system in Pseudomonas aeruginosa involving a protein secreted by a type VI secretion system, the PQS signalling compound and siderophore receptors.

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          Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions.

          Outer-membrane vesicles (OMVs) are spherical buds of the outer membrane filled with periplasmic content and are commonly produced by Gram-negative bacteria. The production of OMVs allows bacteria to interact with their environment, and OMVs have been found to mediate diverse functions, including promoting pathogenesis, enabling bacterial survival during stress conditions and regulating microbial interactions within bacterial communities. Additionally, because of this functional versatility, researchers have begun to explore OMVs as a platform for bioengineering applications. In this Review, we discuss recent advances in the study of OMVs, focusing on new insights into the mechanisms of biogenesis and the functions of these vesicles.
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            Iron and microbial infection.

            The use of iron as a cofactor in basic metabolic pathways is essential to both pathogenic microorganisms and their hosts. It is also a pivotal component of the innate immune response through its role in the generation of toxic oxygen and nitrogen intermediates. During evolution, the shared requirement of micro- and macroorganisms for this important nutrient has shaped the pathogen-host relationship. Here, we discuss how pathogens compete with the host for iron, and also how the host uses iron to counteract this threat.
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              Iron in infection and immunity.

              Iron is an essential nutrient for both humans and pathogenic microbes. Because of its ability to exist in one of two oxidation states, iron is an ideal redox catalyst for diverse cellular processes including respiration and DNA replication. However, the redox potential of iron also contributes to its toxicity; thus, iron concentration and distribution must be carefully controlled. Given the absolute requirement for iron by virtually all human pathogens, an important facet of the innate immune system is to limit iron availability to invading microbes in a process termed nutritional immunity. Successful human pathogens must therefore possess mechanisms to circumvent nutritional immunity in order to cause disease. In this review, we discuss regulation of iron metabolism in the setting of infection and delineate strategies used by human pathogens to overcome iron-withholding defenses. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group
                2041-1723
                28 March 2017
                2017
                : 8
                : 14888
                Affiliations
                [1 ]State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University , Yangling, Shaanxi 712100, China
                [2 ]Shaanxi Engineering & Technological Research Center for Conversation & Utilization of Regional Biological Resources, College of Life Sciences, Yan'an University , Yan'an, Shaanxi 716000, China
                [3 ]Division of Life Science, Hong Kong University of Science and Technology , Clear Water Bay, Hong Kong
                [4 ]Purdue Institute of Immunology, Inflammation and Infectious Diseases and the Department of Biological Sciences, Purdue University , 915 West State Street, West Lafayette, Indiana 47907, USA
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                ncomms14888
                10.1038/ncomms14888
                5379069
                28348410
                b343b122-6397-4d9c-8adb-29ec4ca7f59f
                Copyright © 2017, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 12 September 2016
                : 09 February 2017
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