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Additionally, the metabolic adaptation of\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    to nonrespiratory conditions encountered during infection (e.g., hypoxia, nitric oxide, iron chelation) has been implicated as contributing to\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    virulence. Specifically,\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    has been shown to ferment glycolytic substrates in nonrespiratory environments encountered within the host. Here, we show that\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    has acquired unique carbohydrate transporters that facilitate the maximal uptake of host sugars and serve to support nonrespiratory growth in inflamed tissue. The carbohydrate substrates of 11\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    transporters were identified, and at least four of their genes encode\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    glucose transporters (\n                    <jats:italic>glcA<\/jats:italic>\n                    ,\n                    <jats:italic>glcB<\/jats:italic>\n                    ,\n                    <jats:italic>glcC<\/jats:italic>\n                    , and\n                    <jats:italic>glcU<\/jats:italic>\n                    ). Moreover, two transporter genes (\n                    <jats:italic>glcA<\/jats:italic>\n                    and\n                    <jats:italic>glcC<\/jats:italic>\n                    ) are unique to\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    and contribute disproportionately to the nonrespiratory growth of\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    on glucose. Targeted inactivation of sugar transporters reduced glucose uptake and attenuated\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    in a murine model of skin and soft tissue infections. These data expand the evidence for metabolic adaptation of\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    to invasive infection and demonstrate the specific requirement for the fermentation of glucose over all other available carbohydrates. Ultimately, acquisition of foreign genes allows\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    to adopt a metabolic strategy resembling that of infiltrating host immune cells: high glycolytic flux coupled to lactate excretion.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    The bacterial pathogen\n                    <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n                    causes a wide range of human infections that are costly and difficult to treat.\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    differs from closely related commensal staphylococci in its ability to flourish following the invasion of deeper tissue from the skin surface. There,\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    primarily uses glucose to grow under respiration-limiting conditions imposed by the immune system. It was previously unclear how\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    thrives in this environment when other\n                    <jats:italic>Staphylococcus<\/jats:italic>\n                    species cannot. Our results provide evidence that\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    has acquired an expanded repertoire of carbohydrate transporters. In particular, four glucose transporters contribute to efficient\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    growth during infection. Thus,\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    has evolved to maximize its glucose uptake abilities for enhanced glycolytic flux during tissue invasion. This dependence on glucose acquisition for\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    virulence may also explain links between serious infectious complications associated with diabetic patients exhibiting elevated blood glucose levels.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00296-16","type":"journal-article","created":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T13:13:59Z","timestamp":1466687639000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":122,"title":["Expanded Glucose Import Capability Affords Staphylococcus aureus Optimized Glycolytic Flux during Infection"],"prefix":"10.1128","volume":"7","author":[{"given":"Nicholas P.","family":"Vitko","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda R.","family":"Grosser","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dal","family":"Khatri","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thurlow R.","family":"Lance","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-144-5-200603070-00006"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annemergmed.2010.11.024"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.22.2976"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2009.03.004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/143.4.509"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00109-13"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.9.4987-4996.2002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(98)01400-0"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2013.11.004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2010.06.016"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016957"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028824"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1155207"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.11.012"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020087"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00045-15"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-090110-102851"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-6-r63"},{"key":"e_1_3_2_20_2","first-page":"385","article-title":"Carbohydrate transport in bacteria","volume":"44","author":"Dills SS","year":"1980","unstructured":"Dills SS, Apperson A, Schmidt MR, Saier MH. 1980. 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