{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:21:55Z","timestamp":1785860515475,"version":"3.56.0"},"reference-count":63,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI139400"],"award-info":[{"award-number":["R21AI139400"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["16GRNT27650010"],"award-info":[{"award-number":["16GRNT27650010"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The group A <jats:italic>Streptococcus<\/jats:italic> (GAS) causes diseases that range from mild (e.g. pharyngitis) to severely invasive (e.g. necrotizing fasciitis). Strain\u2010 and serotype\u2010specific differences influence the ability of isolates to cause individual diseases. At the center of this variability is the CovR\/S two\u2010component system and the accessory protein RocA. Through incompletely defined mechanisms, CovR\/S and RocA repress the expression of more than a dozen immunomodulatory virulence factors. Alleviation of this repression is selected for during invasive infections, leading to the recovery of <jats:italic>covR<\/jats:italic>, <jats:italic>covS<\/jats:italic> or <jats:italic>rocA<\/jats:italic> mutant strains. Here, we investigated how RocA promotes CovR\/S activity, identifying that RocA is a pseudokinase that interacts with CovS. Disruption of CovS kinase or phosphatase activities abolishes RocA function, consistent with RocA acting through the modulation of CovS activity. We also identified, in conflict with a previous study, that the RocA regulon includes the secreted protease\u2010encoding gene <jats:italic>speB<\/jats:italic>. Finally, we discovered an inverse correlation between the virulence of wild\u2010type, <jats:italic>rocA<\/jats:italic> mutant, <jats:italic>covS<\/jats:italic> mutant and <jats:italic>covR<\/jats:italic> mutant strains during invasive infection and their fitness in an <jats:italic>ex vivo<\/jats:italic> upper respiratory tract model. Our data inform on mechanisms that control GAS disease potential and provide an explanation for observed strain\u2010 and serotype\u2010specific variability in RocA function.<\/jats:p>","DOI":"10.1111\/mmi.14410","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T12:04:25Z","timestamp":1572350665000},"page":"190-207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The group A <i>Streptococcus<\/i> accessory protein RocA: regulatory activity, interacting partners and influence on disease potential"],"prefix":"10.1111","volume":"113","author":[{"given":"Ira","family":"Jain","sequence":"first","affiliation":[{"name":"Department of Microbiology &amp; Immunology University of Nevada, Reno School of Medicine Reno Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Danger","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology University of Nevada, Reno School of Medicine Reno Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Burgess","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology University of Nevada, Reno School of Medicine Reno Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timsy","family":"Uppal","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology University of Nevada, Reno School of Medicine Reno Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0093-4159","authenticated-orcid":false,"given":"Paul","family":"Sumby","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology University of Nevada, Reno School of Medicine Reno Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061655"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2012.07.018"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00467-18"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.3.595-600.2004"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.10.3081-3090.2003"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05360-11"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01639-13"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-092611-150039"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4258"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00681-18"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05649.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-5804fje"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.3.470"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00257-15"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705972114"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/319291"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.12.3649-3657.1999"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00790-16"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003179"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1739009"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202353699"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05818.x"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00198-06"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1086\/653124"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12250"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004088"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02659-14"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00835-16"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000832"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00274-17"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz195"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00127"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0343-1"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13047"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.10.5752"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(03)00098-2"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.01057.x"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01458-13"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503671102"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003842"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01495-19"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1159\/000219375"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12742"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13136"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1403138111"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.17.5166-5174.2003"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2011.208"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir825"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00288-17"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006917"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07427.x"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13584"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00519-18"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505839102"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2009.12.013"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1086\/432514"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020005"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01354-07"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01560-08"},{"key":"e_1_2_6_61_1","first-page":"337","volume-title":"Streptococcus pyogenes: basic biology to clinical manifestations","author":"Vega L.A.","year":"2016"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.605394"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1128\/genomeA.00221-15"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1128\/mSphereDirect.00460-17"}],"container-title":["Molecular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fmmi.14410","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mmi.14410","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/mmi.14410","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mmi.14410","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T21:22:19Z","timestamp":1694035339000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/mmi.14410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,11]]},"references-count":63,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1111\/mmi.14410"],"URL":"https:\/\/doi.org\/10.1111\/mmi.14410","archive":["Portico"],"relation":{},"ISSN":["0950-382X","1365-2958"],"issn-type":[{"value":"0950-382X","type":"print"},{"value":"1365-2958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,11]]},"assertion":[{"value":"2019-10-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}