{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:34:03Z","timestamp":1792647243412,"version":"4.5.0"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,7,12]],"date-time":"2006-07-12T00:00:00Z","timestamp":1152662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    is a highly virulent human pathogen with an extensive array of strategies to subvert the innate immune response. An important aspect of innate immunity is the production of the nitrogen monoxide radical (Nitric Oxide, NO\u00b7). Here we describe an adaptive response to nitrosative stress that allows\n                    <jats:italic>S.\u2003aureus<\/jats:italic>\n                    to replicate at high concentrations of NO\u00b7. Microarray analysis revealed 84 staphylococcal genes with significantly altered expression following NO\u00b7 exposure. Of these, 30 are involved with iron\u2010homeostasis, potentially under the control of the Fur regulator. Another seven induced genes are involved in hypoxic\/fermentative metabolism, including the flavohaemoprotein, Hmp. The SrrAB two\u2010component system has been shown to regulate the expression of many of the NO\u00b7\u2010induced metabolic genes. Indeed, inactivation of\n                    <jats:italic>hmp<\/jats:italic>\n                    ,\n                    <jats:italic>srrAB<\/jats:italic>\n                    and\n                    <jats:italic>fur<\/jats:italic>\n                    resulted in heightened NO\u00b7 sensitivity. Hmp was responsible for\n                    <jats:italic>c.<\/jats:italic>\n                    90% of measurable staphylococcal NO\u00b7 consumption and therefore critical for efficient NO\u00b7 detoxification. While SrrAB was required for maximal\n                    <jats:italic>hmp<\/jats:italic>\n                    expression,\n                    <jats:italic>srrAB<\/jats:italic>\n                    mutants still exhibited significant NO\u00b7 scavenging and NO\u00b7\u2010dependent induction of\n                    <jats:italic>hmp<\/jats:italic>\n                    . Yet\n                    <jats:italic>S.\u2003aureus<\/jats:italic>\n                    lacking SrrAB were more sensitive to nitrosative stress than\n                    <jats:italic>hmp<\/jats:italic>\n                    mutants, indicating that the contribution of SrrAB to NO\u00b7 resistance extends beyond the regulation of\n                    <jats:italic>hmp<\/jats:italic>\n                    expression. Both Hmp and SrrAB were required for full virulence in a murine sepsis model, however, only the attenuation of the\n                    <jats:italic>hmp<\/jats:italic>\n                    mutant was restored by the abrogation of host NO\u00b7 production. Thus, the\n                    <jats:italic>S.\u2003aureus<\/jats:italic>\n                    Hmp protein has evolved to serve as an iNOS\u2010dependent virulence determinant.\n                  <\/jats:p>","DOI":"10.1111\/j.1365-2958.2006.05290.x","type":"journal-article","created":{"date-parts":[[2006,7,12]],"date-time":"2006-07-12T08:44:27Z","timestamp":1152693867000},"page":"927-939","source":"Crossref","is-referenced-by-count":226,"title":["The nitrosative stress response of\n                    <i>Staphylococcus aureus<\/i>\n                    is required for resistance to innate immunity"],"prefix":"10.1111","volume":"61","author":[{"given":"Anthony R.","family":"Richardson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Dunman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferric C.","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.3.874-881.2006"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"22785","DOI":"10.1016\/S0021-9258(18)54420-3","article-title":"Marker exchange of the structural genes for nitric oxide reductase blocks the denitrification pathway of Pseudomonas stutzeri at nitric oxide","volume":"266","author":"Braun C.","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1997.tb10387.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.cellsig.2005.10.005","article-title":"Lipoteichoic acid\u2010induced nitric oxide synthase expression in RAW 264.7 macrophages is mediated by cyclooxygenase\u20102, prostaglandin E(2), protein kinase A, p38 MAPK, and nuclear factor\u2010kappaB pathways","volume":"18","author":"Chang Y.C.","year":"2005","journal-title":"Cell Signal"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.4.1648-1659.2006"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm728"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf339"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.252591299"},{"key":"e_1_2_6_10_1","first-page":"231","volume-title":"Nitric Oxide and Infection","author":"De Groote M.A.a.F.C.F.","year":"1999"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5260.414"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.12.4046-4050.2004"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410393200"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1289"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04368.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10378"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110471200"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.02.039"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5704"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181199698"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.2.468-475.2001"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02944.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E05-05-0435"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.11.3486-3493.1999"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411070200"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.1.69-76.1996"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.26353-0"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.23.6928-6937.2003"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.13.3803-3808.1996"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.28124-0"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx00040a013"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.49.29350"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050846"},{"key":"e_1_2_6_34_1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.4049\/jimmunol.160.1.308","article-title":"Septic arthritis following Staphylococcus aureus infection in mice lacking inducible nitric oxide synthase","volume":"160","author":"McInnes I.B.","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64492-6"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115903"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107963"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.032066599"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.14.4655-4664.2004"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.2.972-979.2004"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307741100"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2005.05.017"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.6.1783-1787.2002"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx049879c"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(91)04029-N"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2003.00307.x"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2003.11.005"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.124.1.201-211.1975"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200731200"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0330176"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.18.5487-5492.1996"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.8.2430-2438.2004"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(91)90224-7"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.7.2593-2603.2006"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0010055"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.12.014"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1997.4431456.x"},{"key":"e_1_2_6_58_1","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1128\/IAI.66.3.1017-1022.1998","article-title":"Protective role of nitric oxide in Staphylococcus aureus infection in mice","volume":"66","author":"Sasaki S.","year":"1998","journal-title":"Infect Immun"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1033133100"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2003.10.006"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.8.4399-4405.2002"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0102959"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.3.715-723.2004"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh694"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(99)00032-8"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.1.243-247.1997"},{"key":"e_1_2_6_67_1","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1128\/iai.26.3.1159-1163.1979","article-title":"Localization of the third component of complement on the cell wall of encapsulated Staphylococcus aureus M: implications for the mechanism of resistance to phagocytosis","volume":"26","author":"Wilkinson B.J.","year":"1979","journal-title":"Infect Immun"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(98)00092-6"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1948068"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.4.1113-1123.2001"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.15.4639-4643.1999"}],"container-title":["Molecular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2958.2006.05290.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2958.2006.05290.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T04:01:31Z","timestamp":1695960091000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2958.2006.05290.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,7,12]]},"references-count":70,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2006,8]]}},"alternative-id":["10.1111\/j.1365-2958.2006.05290.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2958.2006.05290.x","archive":["Portico"],"relation":{},"ISSN":["0950-382X","1365-2958"],"issn-type":[{"value":"0950-382X","type":"print"},{"value":"1365-2958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,7,12]]}}}