{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T10:30:15Z","timestamp":1762252215739},"reference-count":81,"publisher":"American Society for Microbiology","issue":"15","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"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":["J Bacteriol"],"published-print":{"date-parts":[[2015,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Infection with\n Streptococcus pyogenes<\/jats:named-content>\n is associated with a breadth of clinical manifestations ranging from mild pharyngitis to severe necrotizing fasciitis. Elevated levels of intracellular copper are highly toxic to this bacterium, and thus, the microbe must tightly regulate the level of this metal ion by one or more mechanisms, which have, to date, not been clearly defined. In this study, we have identified two virulence mechanisms by which\n S. pyogenes<\/jats:named-content>\n protects itself against copper toxicity. We defined a set of putative genes,\n copY<\/jats:italic>\n (for a regulator),\n copA<\/jats:italic>\n (for a P1-type ATPase), and\n copZ<\/jats:italic>\n (for a copper chaperone), whose expression is regulated by copper. Our results indicate that these genes are highly conserved among a range of clinical\n S. pyogenes<\/jats:named-content>\n isolates. The\n copY<\/jats:italic>\n ,\n copA<\/jats:italic>\n , and\n copZ<\/jats:italic>\n genes are induced by copper and are transcribed as a single unit. Heterologous expression assays revealed that\n S. pyogenes<\/jats:named-content>\n CopA can confer copper tolerance in a copper-sensitive\n Escherichia coli<\/jats:named-content>\n mutant by preventing the accumulation of toxic levels of copper, a finding that is consistent with a role for CopA in copper export. Evaluation of the effect of copper stress on\n S. pyogenes<\/jats:named-content>\n in a planktonic or biofilm state revealed that biofilms may aid in protection during initial exposure to copper. However, copper stress appears to prevent the shift from the planktonic to the biofilm state. Therefore, our results indicate that\n S. pyogenes<\/jats:named-content>\n may use several virulence mechanisms, including altered gene expression and a transition to and from planktonic and biofilm states, to promote survival during copper stress.\n <\/jats:p>\n \n IMPORTANCE<\/jats:bold>\n Bacterial pathogens encounter multiple stressors at the host-pathogen interface. This study evaluates a virulence mechanism(s) utilized by\n S. pyogenes<\/jats:named-content>\n to combat copper at sites of infection. A better understanding of pathogen tolerance to stressors such as copper is necessary to determine how host-pathogen interactions impact bacterial survival during infections. These insights may lead to the identification of novel therapeutic targets that can be used to address antibiotic resistance.\n <\/jats:p>","DOI":"10.1128\/jb.00127-15","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T15:25:06Z","timestamp":1432740306000},"page":"2580-2592","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Copper Tolerance and Characterization of a Copper-Responsive Operon,\n copYAZ<\/i>\n , in an M1T1 Clinical Strain of Streptococcus pyogenes"],"prefix":"10.1128","volume":"197","author":[{"given":"Christie A.","family":"Young","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lily D.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert C.","family":"Holder","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean D.","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.3.470-511.2000"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-73960-1_3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(03)00576-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/315922"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.9.4968-4976.2002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01299-08"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4161\/viru.21933"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-009-0588-3"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/7171_2006_081","volume-title":"Molecular microbiology of heavy metals","author":"Magnani D","year":"2007","unstructured":"Magnani D, Solioz M. 2007. 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