{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:59:52Z","timestamp":1773820792775,"version":"3.50.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    In the living world, copper is both toxic in excess and necessary for the activity of specific oxidoreductases and electron transfer chains and as such is involved in the host-pathogen interface. Mammalian hosts deploy anti-microbial strategies of copper intoxication or starvation of invading microorganisms, collectively called nutritional immunity, and bacteria have developed both protection and acquisition systems in response. We recently described a TonB-dependent copper importer, CrtA\n                    <jats:sup>Bp<\/jats:sup>\n                    in the whooping cough agent\n                    <jats:italic>Bordetella pertussis<\/jats:italic>\n                    . Here we characterized another protein encoded in the same operon and similarly upregulated by copper starvation, CrpH. By combining\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    experiments with transcriptomics, we showed that CrpH contributes to bacterial fitness and enhances respiration by the heme-copper oxidoreductases (HCO) of\n                    <jats:italic>B. pertussis<\/jats:italic>\n                    . CrpH belongs to the PepSY_TM superfamily of membrane-associated bacterial enzymes, whose known members catalyze heme-mediated ferrisiderophore reduction in the periplasm. The corresponding heme-binding motifs of CrpH are similarly required for function. Furthermore, we uncovered a synthetic growth phenotype of a double\n                    <jats:italic>crpH<\/jats:italic>\n                    -\n                    <jats:italic>ccoG<\/jats:italic>\n                    mutant, the latter gene encoding a putative copper reductase involved in HCO assembly.\n                    <jats:italic>In silico<\/jats:italic>\n                    analyses identified thousands of CrpH orthologs, leading us to define a new subfamily of PepSY_TM proteins found in diverse bacterial species all harboring HCO genes. Collectively, our results indicate that CrpH of\n                    <jats:italic>B. pertussis<\/jats:italic>\n                    is a prototype of a family of proteins supporting HCO function.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1786092","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:57:54Z","timestamp":1773817074000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CrpH of Bordetella pertussis, a prototypic PepSY_TM protein supporting heme-copper oxidoreductase function"],"prefix":"10.3389","volume":"17","author":[{"given":"Majda","family":"Hachmi","sequence":"first","affiliation":[{"name":"University of Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Center for Infection and Immunity of Lille","place":["Lille, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gauthier","family":"Roy","sequence":"additional","affiliation":[{"name":"University of Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Center for Infection and Immunity of Lille","place":["Lille, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Sophie","family":"Debrie","sequence":"additional","affiliation":[{"name":"University of Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Center for Infection and Immunity of Lille","place":["Lille, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phanie","family":"Slupek","sequence":"additional","affiliation":[{"name":"University of Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Center for Infection and Immunity of Lille","place":["Lille, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudy","family":"Antoine","sequence":"additional","affiliation":[{"name":"University of Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Center for Infection and Immunity of Lille","place":["Lille, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7oise","family":"Jacob-Dubuisson","sequence":"additional","affiliation":[{"name":"University of Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Center for Infection and Immunity of Lille","place":["Lille, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"32431","DOI":"10.1074\/jbc.M114.607127","article-title":"How periplasmic thioredoxin TlpA reduces bacterial copper chaperone ScoI and cytochrome oxidase subunit II (CoxB) prior to metallation","volume":"289","author":"Abicht","year":"2014","journal-title":"J. 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