{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:47:46Z","timestamp":1790966866773,"version":"4.1.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The bacterial pathogen group A<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptococcus<\/jats:named-content>(GAS) causes human diseases ranging from self-limiting pharyngitis (also known as strep throat) to severely invasive necrotizing fasciitis (also known as the flesh-eating syndrome). To control virulence factor expression, GAS utilizes both protein- and RNA-based mechanisms of regulation. Here we report that the transcription factor RivR (RofA-like protein IV) negatively regulates the abundance of mRNAs encoding the hyaluronic acid capsule biosynthesis proteins (<jats:italic>hasABC<\/jats:italic>; \u223c7-fold) and the protein G-related \u03b1<jats:sub>2<\/jats:sub>-macroglobulin-binding protein (<jats:italic>grab<\/jats:italic>; \u223c29-fold). Our data differ significantly from those of a previous study of the RivR regulon. Given that<jats:italic>grab<\/jats:italic>and<jats:italic>hasABC<\/jats:italic>are also negatively regulated by the two-component system CovR\/S (<jats:underline>c<\/jats:underline>ontrol<jats:underline>o<\/jats:underline>f<jats:underline>v<\/jats:underline>irulence), we tested whether RivR functions through CovR\/S. A comparison of<jats:italic>riv<\/jats:italic>and<jats:italic>cov<\/jats:italic>single and double mutant strains showed that RivR requires CovR activity for<jats:italic>grab<\/jats:italic>and<jats:italic>hasABC<\/jats:italic>regulation. Analysis of the upstream region of<jats:italic>rivR<\/jats:italic>identified a novel promoter the deletion of which reduced<jats:italic>rivR<\/jats:italic>mRNA abundance by 70%. A<jats:italic>rivR<\/jats:italic>mutant strain had a reduced ability to adhere to human keratinocytes relative to that of the parental and complemented strains, a phenotype that was abolished upon GAS pretreatment with hyaluronidase, highlighting the importance of capsule regulation by RivR during colonization. The<jats:italic>rivR<\/jats:italic>mutant strain was also attenuated for virulence in a murine model of bacteremia infection. Thus, we identify RivR as an important regulator of GAS virulence and provide new insight into the regulatory networks controlling virulence factor production in this pathogen.<\/jats:p>","DOI":"10.1128\/iai.00703-12","type":"journal-article","created":{"date-parts":[[2012,11,13]],"date-time":"2012-11-13T12:05:45Z","timestamp":1352808345000},"page":"364-372","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["RivR Is a Negative Regulator of Virulence Factor Expression in Group A Streptococcus"],"prefix":"10.1128","volume":"81","author":[{"given":"Jeanette","family":"Trevi\u00f1o","sequence":"first","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuyun","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tram N.","family":"Cao","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmeralda","family":"Ramirez-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Sumby","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"},{"name":"Department of Pathology and Genomic Medicine, The Methodist Hospital System, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.3.470"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.19.8317"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2121"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945012799424589"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.22.15336"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(03)00098-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01658-06"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-5-1501"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003450"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2012.08178.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.01057.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.22.6619-6624.1995"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05381.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.06006.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0636231100"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020005"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202353699"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.12.3649-3657.1999"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01560-08"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01026-06"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00597-08"},{"key":"e_1_3_3_23_2","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1111\/j.1365-2958.2007.06015.x","article-title":"RivR and the small RNA RivX: the missing links between the CovR regulatory cascade and the Mga regulon","volume":"66","author":"Roberts SA","year":"2007","unstructured":"RobertsSAScottJR. 2007. 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