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The facultative intracellular pathogen employs a bipartite metabolism, where the amino acid serine serves as the major energy supply, while glycerol and glucose are mainly utilized for anabolic processes. The\n            <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n            genome harbors the cluster\n            <jats:italic>lpg1653<\/jats:italic>\n            to\n            <jats:italic>lpg1649<\/jats:italic>\n            putatively involved in the metabolism of the abundant carbohydrate\n            <jats:italic>myo<\/jats:italic>\n            -inositol (here termed inositol). To assess inositol metabolism by\n            <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n            , we constructed defined mutant strains lacking\n            <jats:italic>lpg1653<\/jats:italic>\n            or\n            <jats:italic>lpg1652<\/jats:italic>\n            , which are predicted to encode the inositol transporter IolT or the inositol-2-dehydrogenase IolG, respectively. The mutant strains were not impaired for growth in complex or defined minimal media, and inositol did not promote extracellular growth. However, upon coinfection of\n            <jats:named-content content-type=\"genus-species\">Acanthamoeba castellanii<\/jats:named-content>\n            , the mutants were outcompeted by the parental strain, indicating that the intracellular inositol metabolism confers a fitness advantage to the pathogen. Indeed, inositol added to\n            <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n            -infected amoebae or macrophages promoted intracellular growth of the parental strain, but not of the \u0394\n            <jats:italic>iolT<\/jats:italic>\n            or \u0394\n            <jats:italic>iolG<\/jats:italic>\n            mutant, and growth stimulation by inositol was restored by complementation of the mutant strains. The expression of the P\n            <jats:sub>\n              <jats:italic>iol<\/jats:italic>\n            <\/jats:sub>\n            promoter and bacterial uptake of inositol required the alternative sigma factor RpoS, a key virulence regulator of\n            <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n            . Finally, the parental strain and \u0394\n            <jats:italic>iolG<\/jats:italic>\n            mutant bacteria but not the \u0394\n            <jats:italic>iolT<\/jats:italic>\n            mutant strain accumulated [U-\n            <jats:sup>14<\/jats:sup>\n            C\n            <jats:sub>6<\/jats:sub>\n            ]inositol, indicating that IolT indeed functions as an inositol transporter. Taken together, intracellular\n            <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n            metabolizes inositol through the\n            <jats:italic>iol<\/jats:italic>\n            gene products, thus promoting the growth and virulence of the pathogen.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            The environmental bacterium\n            <jats:named-content content-type=\"genus-species\">Legionella pneumophila<\/jats:named-content>\n            is the causative agent of a severe pneumonia termed Legionnaires' disease. The opportunistic pathogen replicates in protozoan and mammalian phagocytes in a unique vacuole. Amino acids are thought to represent the prime source of carbon and energy for\n            <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n            . However, genome, transcriptome, and proteome studies indicate that the pathogen not only utilizes amino acids as carbon sources but possesses broader metabolic capacities. In this study, we analyzed the metabolism of inositol by extra- and intracellularly growing\n            <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n            . By using genetic, biochemical, and cell biological approaches, we found that\n            <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n            accumulates and metabolizes inositol through the\n            <jats:italic>iol<\/jats:italic>\n            gene products, thus promoting the intracellular growth, virulence, and fitness of the pathogen. Our study significantly contributes to an understanding of the intracellular niche of a human pathogen.\n          <\/jats:p>","DOI":"10.1128\/aem.01018-16","type":"journal-article","created":{"date-parts":[[2016,6,11]],"date-time":"2016-06-11T05:20:17Z","timestamp":1465622417000},"page":"5000-5014","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Metabolism of\n            <i>myo<\/i>\n            -Inositol by Legionella pneumophila Promotes Infection of Amoebae and Macrophages"],"prefix":"10.1128","volume":"82","author":[{"given":"Christian","family":"Manske","sequence":"first","affiliation":[{"name":"Max von Pettenkofer Institute, Ludwig Maximilians University, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Schell","sequence":"additional","affiliation":[{"name":"Max von Pettenkofer Institute, Ludwig Maximilians University, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Hilbi","sequence":"additional","affiliation":[{"name":"Max von Pettenkofer Institute, Ludwig Maximilians University, Munich, Germany"},{"name":"Institute of Medical Microbiology, University of Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms141121660"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1758-2229.2011.00247.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.72.4.2885-2895.2006"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842X(96)10041-X"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12235"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00052-09"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1967"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100109-104034"},{"key":"e_1_3_3_10_2","first-page":"155","article-title":"Phosphoinositide lipids and the Legionella pathogen vacuole","volume":"376","author":"Haneburger I","year":"2013","unstructured":"Haneburger I, Hilbi H. 2013. 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