{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:40:22Z","timestamp":1792510822899,"version":"4.5.0"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a T\u011blov\u00fdchovy","doi-asserted-by":"publisher","award":["JAC CZ.02.01.01\/00\/22_008\/0004575"],"award-info":[{"award-number":["JAC CZ.02.01.01\/00\/22_008\/0004575"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Bordetella pertussis<\/jats:italic>\n                      is a strictly human, re-emerging respiratory pathogen and the causative agent of whooping cough. Through its adaptation to humans,\n                      <jats:italic toggle=\"yes\">B. pertussis<\/jats:italic>\n                      decayed or lost genes of the sulfate assimilation pathway and, consequently, must obtain cysteine from the host. Previously, we showed that the sulfur metabolism of\n                      <jats:italic toggle=\"yes\">B. pertussis<\/jats:italic>\n                      is substantially rewired during infection of human macrophages. Here, we investigated the role of several cysteine metabolism- and transport-related genes in the fitness and virulence of this pathogen. We show that excess cysteine strongly induces the expression of genes encoding two cysteine dioxygenase (CDO) homologs, BP2871 and BP3011, and a putative sulfite exporter, BP2808. The mutant lacking both cysteine dioxygenase genes exhibits impaired growth and severely reduced secretion of pertussis toxin under excess cysteine conditions\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and attenuated virulence\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Intriguingly, both cysteine dioxygenases contain a cysteine residue near the active site, a feature typical of mammalian enzymes and associated with increased activity and stability of CDOs. Notably, replacing this cysteine with glycine in both CDOs led to impaired growth of the mutant and slightly reduced secretion of pertussis toxin and cytotoxicity. We also demonstrate the essential role of the sulfite exporter BP2808 and \u03b3-glutamyl-cysteine synthase BP0598 in the adaptation of\n                      <jats:italic toggle=\"yes\">B. pertussis<\/jats:italic>\n                      to cysteine-induced stress. Overall, our data suggest that sulfur metabolism has been effectively streamlined in\n                      <jats:italic toggle=\"yes\">B. pertussis<\/jats:italic>\n                      and plays an important role at the host-pathogen interface.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Sulfur is one of the essential nutrients required by cells for growth, and cysteine is central to sulfur metabolism. While most bacteria prefer environmentally available sulfate as their cysteine source, several bacterial pathogens rely on cysteine provided by the host. Here, we show that\n                        <jats:italic toggle=\"yes\">Bordetella pertussis<\/jats:italic>\n                        , the causative agent of whooping cough, has simplified its sulfur metabolism. Our data suggest that two cysteine dioxygenase homologs and sulfite exporter play key roles in sulfur homeostasis and redox balance. Both dioxygenases enable the pathogen to use cysteine as a source of sulfur, and the sulfite exporter removes the toxic byproduct of cysteine conversion. Importantly, the lack of cysteine dioxygenase activity leads to aberrant secretion of pertussis toxin, one of the essential virulence factors, resulting in attenuated virulence of the pathogen. We suggest that cysteine auxotrophy can be considered part of an infection strategy that assists\n                        <jats:italic toggle=\"yes\">B. pertussis<\/jats:italic>\n                        in adaptation to its human host.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01414-26","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T13:00:39Z","timestamp":1787144439000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Two cysteine dioxygenase homologs contribute to the fitness and virulence of a human pathogen"],"prefix":"10.1128","volume":"14","author":[{"given":"Argha","family":"Saha","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047yhep71","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Post-transcriptional Control of Gene expression, Institute of Microbiology of the ASCR","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisa","family":"Petr\u00e1\u010dkov\u00e1","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047yhep71","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Post-transcriptional Control of Gene expression, Institute of Microbiology of the ASCR","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Holubov\u00e1","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047yhep71","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the ASCR","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Beles","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047yhep71","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Post-transcriptional Control of Gene expression, Institute of Microbiology of the ASCR","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"\u010curnov\u00e1","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047yhep71","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Post-transcriptional Control of Gene expression, Institute of Microbiology of the ASCR","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ond\u0159ej","family":"Stan\u011bk","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047yhep71","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the ASCR","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9520-6324","authenticated-orcid":true,"given":"Branislav","family":"Ve\u010derek","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047yhep71","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Post-transcriptional Control of Gene expression, Institute of Microbiology of the ASCR","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01637.x"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1022"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2023.06.010"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/ecosalplus.3.6.1.11"},{"key":"e_1_3_5_6_2","first-page":"145","article-title":"Sulfur metabolism in Escherichia coli and related bacteria: facts and fiction","volume":"2","author":"Sekowska A","year":"2000","unstructured":"Sekowska A, Kung HF, Danchin A. 2000. 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