{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:05:05Z","timestamp":1788217505464,"version":"build-2803163510"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI153185"],"award-info":[{"award-number":["AI153185"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI172080"],"award-info":[{"award-number":["AI172080"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX002711"],"award-info":[{"award-number":["BX002711"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2025,10,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      is a Gram-positive opportunistic pathogen and a leading cause of skin and soft tissue infections (SSTIs).\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      colonizes approximately 20\u201330% of the population and transiently colonizes the skin. Although skin colonization is an SSTI risk factor, our understanding of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      requirements to persist in this environment is still developing. The human skin is acidic, with a ubiquitous distribution of eccrine glands, which secrete metabolites, such as urea onto the skin surface. Many pathogens break down urea into ammonia and carbon dioxide by the Ni(II)-dependent enzyme urease as an acid resistance mechanism.\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      relies on urea metabolism for pH homeostasis in the murine kidney, but a role for this process on skin has not been shown. Using an\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      model of the human skin surface environment, we investigated the role of urease in the methicillin-resistant USA300 strain\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      subsp.\n                      <jats:italic toggle=\"yes\">aureus<\/jats:italic>\n                      (MRSA) LAC. We observe that urease contributes to an increase in extracellular pH and production of extracellular ammonium, which results in ammonium becoming a shared good in a mixed culture. We also demonstrate that the putative urea transporter SAUSA300_2237 (\n                      <jats:italic toggle=\"yes\">ureT<\/jats:italic>\n                      ) is required for optimal extracellular ammonia generation. Finally, we show that the urease inhibitor fluorofamide effectively inhibits\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      urease activity. This work identifies a role for urea metabolism during\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      skin colonization and offers the first published characterization of the\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      putative urea transporter, UreT.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The human skin is a unique microbial environment that has been challenging to faithfully model in the laboratory. Here, we utilize a recently developed media recipe incorporating metabolites measured from healthy human skin to assess the role of urease in\n                        <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                        pH homeostasis in the skin environment. These data provide new insights into the role of urea metabolism in\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        pH homeostasis during skin colonization. We also describe the first characterization of transporter SAUSA300_2237 (\n                        <jats:italic toggle=\"yes\">ureT<\/jats:italic>\n                        ) and demonstrate its role in urea metabolism. These insights advance our understanding of this metabolic pathway in\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        .\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00208-25","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T13:00:37Z","timestamp":1757336437000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Urease promotes pH homeostasis and growth of\n                    <i>Staphylococcus aureus<\/i>\n                    in skin-like conditions"],"prefix":"10.1128","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7058-6009","authenticated-orcid":true,"given":"Flavia G.","family":"Costa","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wmf1y16","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5568-0096","authenticated-orcid":true,"given":"Alexander R.","family":"Horswill","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wmf1y16","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]},{"name":"Department of Veterans Affairs, Eastern Colorado Healthcare System","place":["Aurora, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012677530-3\/50258-0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200101043440102"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.10.3.505"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(05)70295-4"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25179165"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.14489"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-1531"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-2494.2006.00344.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/ics.12068"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2015.06.001"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108924"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00051-14"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.11.012"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-020-01808-w"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.57.1.110-116.1989"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007538"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/23328940.2019.1632145"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01049065"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/0300985811430511"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48226-z"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00453-24"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-54454-x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00028-25"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00537-12"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-52982-0"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02940-06"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010146"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1159\/000319909"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00125-16"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015520"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsle\/fnae100"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00767"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-5378.2001.00014.x"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.34218"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08558"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/lam.12153"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1023\/a:1018884322973"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.10.4832-4837.1998"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.000757"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14404"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ075"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00848-09"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1213344109"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115421"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01022-12"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0016-5085(96)70056-2"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01434-16"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.26512-0"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi200887a"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042244"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00277-11"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(66)90088-1"}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jb.00208-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jb.00208-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T13:21:30Z","timestamp":1761225690000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jb.00208-25"}},"subtitle":[],"editor":[{"given":"Tina M.","family":"Henkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":52,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10,23]]}},"alternative-id":["10.1128\/jb.00208-25"],"URL":"https:\/\/doi.org\/10.1128\/jb.00208-25","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]},"assertion":[{"value":"2025-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00208-25"}}