{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:21:12Z","timestamp":1791512472994,"version":"4.3.4"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"17","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["RO1AI069233"],"award-info":[{"award-number":["RO1AI069233"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["RO1AI073843"],"award-info":[{"award-number":["RO1AI073843"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["NOTO15D0"],"award-info":[{"award-number":["NOTO15D0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n                    and\n                    <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n                    are commonly isolated from polymicrobial infections, such as wound infections and chronic respiratory infections of persons with cystic fibrosis. Despite their coisolation,\n                    <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n                    produces substances toxic to\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    , including pyocyanin, a blue-pigmented molecule that functions in\n                    <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n                    virulence. Pyocyanin inhibits\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    respiration, forcing it to derive energy from fermentation and adopt a small-colony variant (SCV) phenotype. The mechanisms by which\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    sustains infection in the presence of pyocyanin are not clear. We sought to clarify the mechanisms of pyocyanin toxicity in\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    as well as identify the staphylococcal factors involved in its resistance to pyocyanin toxicity. Nonrespiring\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    SCVs are inhibited by pyocyanin through pyocyanin-dependent reactive oxygen species (ROS) production, indicating that pyocyanin toxicity is mediated through respiratory inhibition and ROS generation. Selection on pyocyanin yielded a menadione auxotrophic SCV capable of growth on high concentrations of pyocyanin. Genome sequencing of this isolate identified mutations in four genes, including\n                    <jats:italic>saeS<\/jats:italic>\n                    ,\n                    <jats:italic>menD<\/jats:italic>\n                    , NWMN_0006, and\n                    <jats:italic>qsrR<\/jats:italic>\n                    . QsrR is a quinone-sensing repressor of quinone detoxification genes. Inactivation of\n                    <jats:italic>qsrR<\/jats:italic>\n                    resulted in significant pyocyanin resistance, and additional pyocyanin resistance was achieved through combined inactivation of\n                    <jats:italic>qsrR<\/jats:italic>\n                    and menadione biosynthesis. Pyocyanin-resistant\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    has an enhanced capability to inactivate pyocyanin, suggesting QsrR-regulated gene products may degrade pyocyanin to alleviate toxicity. These findings demonstrate pyocyanin-mediated ROS generation as an additional mechanism of pyocyanin toxicity and define QsrR as a key mediator of pyocyanin resistance in\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    .\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    Many bacterial infections occur in the presence of other microbes, where interactions between different microbes and the host impact disease. In patients with cystic fibrosis, chronic lung infection with multiple microbes results in the most severe disease manifestations.\n                    <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n                    and\n                    <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n                    are prevalent cystic fibrosis pathogens, and infection with both is associated with worse outcomes. These organisms have evolved mechanisms of competing with one another. For example,\n                    <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n                    produces pyocyanin, which inhibits\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    growth. Our research has identified how pyocyanin inhibits\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    growth and how\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    can adapt to survive in the presence of pyocyanin. Understanding how\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    sustains infection in the presence of\n                    <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n                    may identify means of disrupting these microbial communities.\n                  <\/jats:p>","DOI":"10.1128\/jb.00221-17","type":"journal-article","created":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T20:40:12Z","timestamp":1497300012000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":82,"title":["Mechanisms of Pyocyanin Toxicity and Genetic Determinants of Resistance in Staphylococcus aureus"],"prefix":"10.1128","volume":"199","author":[{"given":"Michael J.","family":"Noto","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William N.","family":"Beavers","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P.","family":"Skaar","sequence":"additional","affiliation":[{"name":"Tennessee Valley Healthcare System, U.S. Department of Veterans Affairs, Nashville, Tennessee, USA"},{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00081-09"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu410"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043252"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/587893"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-8-43"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-016-2621-0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.791"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.15.1787"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.11.064"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.10127"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1214550110"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-016-7596-3"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11951"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53203-8"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00059-15"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606756104"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01211-09"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00858-06"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1139\/m75-088"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.141.1.156-163.1980"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1384"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00361-08"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit270"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2004.10.002"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.7.4275-4278.2004"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.251465298"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.56.9.2515-2517.1988"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012-0088OC"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00198.2003"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.4.1861"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00025.2004"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2015.10.014"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C111.310847"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219446110"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.5979"},{"key":"e_1_3_3_37_2","doi-asserted-by":"crossref","first-page":"571","DOI":"10.18388\/abp.2008_3063","article-title":"Reactions of Pseudomonas aeruginosa pyocyanin with reduced glutathione","volume":"55","author":"Cheluvappa R","year":"2008","unstructured":"Cheluvappa R Shimmon R Dawson M Hilmer SN Le Couteur DG . 2008. Reactions of Pseudomonas aeruginosa pyocyanin with reduced glutathione. Acta Biochim Pol55:571\u2013580.","journal-title":"Acta Biochim Pol"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209264200"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2015-0102"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-008-8071-8"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2008.09.011"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2011.01727.x"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.62"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.20.6.814"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00555-06"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1086\/515238"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.45.2.316-354.1981"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00241-13"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1081147"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-6-1-2-95"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12063"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.6b00081"}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.00221-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.00221-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T13:43:33Z","timestamp":1627566213000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JB.00221-17"}},"subtitle":[],"editor":[{"given":"George","family":"O'Toole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,9]]},"references-count":51,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1128\/JB.00221-17"],"URL":"https:\/\/doi.org\/10.1128\/jb.00221-17","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727714317.793534365","asserted-by":"object"}]},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9]]},"assertion":[{"value":"2017-03-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-08-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}