{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:13:52Z","timestamp":1783660432306,"version":"3.55.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Tryptophan plays a key role in regulating human lung homeostasis and immunity through the indoleamine 2,3-dioxygenase (IDO) and aryl hydrocarbon receptor (AhR) signalling pathways. In patients with chronic obstructive pulmonary disease (COPD), altered IDO and AhR activity is observed, potentially favouring infection by pathogens capable of synthesizing their own tryptophan. In this study, we investigated the contribution of tryptophan availability to lung infection by\n                      <jats:italic>Haemophilus influenzae<\/jats:italic>\n                      , a tryptophan synthesizing pathobiont associated with COPD exacerbations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A chemically defined medium with controlled tryptophan levels was developed, and used to determine bacterial (i) metabolite consumption\/excretion; (ii) genome-wide differential gene expression and post-transcriptional regulation; (iii)\n                      <jats:italic>in vivo<\/jats:italic>\n                      growth in a murine model of lung infection; and (iv) growth upon tryptophan biosynthesis allosteric inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Under tryptophan-rich conditions, we observed up-regulation of\n                      <jats:italic>tnaA<\/jats:italic>\n                      (encoding a tryptophanase) and\n                      <jats:italic>tnaB<\/jats:italic>\n                      (encoding a tryptophan transporter), accompanied by down-regulation of tryptophan biosynthetic genes. Furthermore, transcriptomic analysis combined with the ExcludonFinder computational tool generated an excludon map of the\n                      <jats:italic>H. influenzae<\/jats:italic>\n                      genome, and identified that the 3\u00b4-UTR regions of the convergent\n                      <jats:italic>mtr<\/jats:italic>\n                      tryptophan transporter and the\n                      <jats:italic>sdaCA<\/jats:italic>\n                      serine transporter-deaminase genes overlap, suggesting a post-transcriptional regulatory link between tryptophan and serine metabolism.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , dietary modulation of tryptophan availability in a murine model supported effective lung infection as long as the bacterial tryptophan biosynthetic pathway remains functional. This biosynthetic requirement is supported by the\n                      <jats:italic>in vitro<\/jats:italic>\n                      growth inhibitory effect of indole propionic acid, a tryptophan derivative acting as TrpE allosteric inhibitor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that\n                      <jats:italic>H. influenzae<\/jats:italic>\n                      \u2019s capacity to synthesize tryptophan is required for infection under host-imposed nutrient limitations, and highlight the potential of tryptophan biosynthesis as a target for antibacterial intervention.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1787089","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:25:52Z","timestamp":1783657552000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Haemophilus influenzae tryptophan biosynthesis is required for lung infection"],"prefix":"10.3389","volume":"16","author":[{"given":"Javier","family":"Asensio-L\u00f3pez","sequence":"first","affiliation":[{"name":"Instituto de Agrobiotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (IdAB-CSIC)-Gobierno de Navarra","place":["Mutilva, Navarra, Spain"]},{"name":"Asociaci\u00f3n de la Industria Navarra (AIN)-Gobierno de Navarra","place":["Cordovilla, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Rap\u00fan-Araiz","sequence":"additional","affiliation":[{"name":"Instituto de Agrobiotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (IdAB-CSIC)-Gobierno de Navarra","place":["Mutilva, Navarra, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Euba","sequence":"additional","affiliation":[{"name":"Instituto de Agrobiotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (IdAB-CSIC)-Gobierno de Navarra","place":["Mutilva, Navarra, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asier","family":"Dom\u00ednguez-San Pedro","sequence":"additional","affiliation":[{"name":"Instituto de Agrobiotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (IdAB-CSIC)-Gobierno de Navarra","place":["Mutilva, Navarra, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Sanmart\u00edn","sequence":"additional","affiliation":[{"name":"Laboratory of Microbial Pathogenesis, Navarrabiomed-Universidad P\u00fablica de Navarra (UPNA)-Complejo Hospitalario de Navarra (CHN), IdiSNA","place":["Pamplona, Navarra, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Gil-Campillo","sequence":"additional","affiliation":[{"name":"Instituto de Agrobiotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (IdAB-CSIC)-Gobierno de Navarra","place":["Mutilva, Navarra, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"San Le\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Centro Nacional de Biotecnolog\u00eda, CSIC","place":["Madrid, Spain"]},{"name":"Interdisciplinary Platform for Sustainable Plastics towards a Circular Economy-Spanish National Research Council (SusPlast-CSIC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Chac\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Biological Physical Chemistry, Blas Cabrera Institute of Physical Chemistry, CSIC","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goizeder","family":"Almagro","sequence":"additional","affiliation":[{"name":"Instituto de Agrobiotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (IdAB-CSIC)-Gobierno de Navarra","place":["Mutilva, Navarra, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Ard\u00e1","sequence":"additional","affiliation":[{"name":"Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Ikerbasque, Basque Foundation for Science","place":["Bilbao, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saioa","family":"Burgui","sequence":"additional","affiliation":[{"name":"Asociaci\u00f3n de la Industria Navarra (AIN)-Gobierno de Navarra","place":["Cordovilla, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I\u00f1igo","family":"Lasa","sequence":"additional","affiliation":[{"name":"Laboratory of Microbial Pathogenesis, Navarrabiomed-Universidad P\u00fablica de Navarra (UPNA)-Complejo Hospitalario de Navarra (CHN), IdiSNA","place":["Pamplona, Navarra, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Toledo-Arana","sequence":"additional","affiliation":[{"name":"Instituto de Agrobiotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (IdAB-CSIC)-Gobierno de Navarra","place":["Mutilva, Navarra, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junkal","family":"Garmendia","sequence":"additional","affiliation":[{"name":"Instituto de Agrobiotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (IdAB-CSIC)-Gobierno de Navarra","place":["Mutilva, Navarra, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES)","place":["Madrid, Spain"]},{"name":"Conexi\u00f3n Antimicrobial Resistance-AMR, CSIC","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut microbiota regulation of tryptophan metabolism in health and disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell. Host Microbe"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2300239","DOI":"10.1183\/13993003.00239-2023","article-title":"Global initiative for chronic obstructive lung disease 2023 report: GOLD executive summary","volume":"61","author":"Agust\u00ed","year":"2023","journal-title":"Eur. Respir. J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"5291","DOI":"10.1128\/iai.73.9.5291-5300.2005","article-title":"Novel sialic acid transporter of Haemophilus influenzae","volume":"73","author":"Allen","year":"2005","journal-title":"Infect. Immun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2911","DOI":"10.1093\/plphys\/kiae263","article-title":"Antisense RNA regulates glutamine synthetase in a heterocyst-forming cyanobacterium","volume":"195","author":"\u00c1lvarez-Escribano","year":"2024","journal-title":"Plant Physiol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01765-15","article-title":"Dual RNA-seq of nontypeable Haemophilus influenzae and host cell transcriptomes reveals novel insights into host-pathogen cross talk","volume":"6","author":"Baddal","year":"2015","journal-title":"mBio"},{"key":"B6","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/nature24661","article-title":"A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites","volume":"551","author":"Dodd","year":"2017","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3840","DOI":"10.1002\/1873-3468.12351","article-title":"Host\u2013pathogen interactions of nontypeable Haemophilus influenzae: from commensal to pathogen","volume":"590","author":"Duell","year":"2016","journal-title":"FEBS Lett."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00823-23","article-title":"In vivo genome-wide gene expression profiling reveals that Haemophilus influenzae pathway benefits its infectivity within the airways","volume":"11","author":"Euba","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00789-21","article-title":"Phase variation in HMW1A controls a phenotypic switch in Haemophilus influenzae associated with pathoadaptation during persistent infection","volume":"12","author":"Fern\u00e1ndez-Calvet","year":"2021","journal-title":"mBio"},{"key":"B11","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1126\/science.7542800","article-title":"Whole-genome random sequencing and assembly of Haemophilus influenzae Rd","volume":"269","author":"Fleischmann","year":"1995","journal-title":"Science"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide:\u2009 A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"E62","DOI":"10.1073\/pnas.1711373114","article-title":"In vivo inhibition of tryptophan catabolism reorganizes the tuberculoma and augments immune-mediated control of Mycobacterium tuberculosis","volume":"115","author":"Gautam","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01355-25","article-title":"Epigenetic control of the ferric uptake regulator (Fur) and fumarate nitrate reductase (FNR) master regulatory proteins contributes to Haemophilus influenzae survival during lung infection","volume":"16","author":"Gil-Campillo","year":"2025","journal-title":"mBio"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1013650","article-title":"CRISPRi-seq in Haemophilus influenzae reveals genome-wide and medium-specific growth determinants","volume":"21","author":"Gil-Campillo","year":"2025","journal-title":"PloS Pathog."},{"key":"B16","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/s1471-4906(03)00072-3","article-title":"Tolerance, DCs and tryptophan: much ado about IDO","volume":"24","author":"Grohmann","year":"2003","journal-title":"Trends Immunol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e21376","DOI":"10.1096\/fj.202002350r","article-title":"Aryl hydrocarbon receptor deficiency causes the development of chronic obstructive pulmonary disease through the integration of multiple pathogenic mechanisms","volume":"35","author":"Guerrina","year":"2021","journal-title":"FASEB J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41522-019-0105-6","article-title":"Reprioritization of biofilm metabolism is associated with nutrient adaptation and long-term survival of Haemophilus influenzae","volume":"5","author":"Harrison","year":"2019","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B19","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1128\/jb.101.2.517-524.1970","article-title":"Defined nongrowth media for stage II development of competence in Haemophilus influenzae","volume":"101","author":"Herriott","year":"1970","journal-title":"J. Bacteriol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1056\/nejmoa0909883","article-title":"Susceptibility to exacerbation in chronic obstructive pulmonary disease","volume":"363","author":"Hurst","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1093\/geroni\/igaa057.403","article-title":"A 3-week tryptophan-deficient diet resulted in decreased body weight and increased trabecular bone mass in mice","volume":"4","author":"Isales","year":"2020","journal-title":"Innov. Aging"},{"key":"B22","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"72","DOI":"10.2165\/00128415-199304360-00058","article-title":"How important is tryptophan in human health","volume":"59","author":"Ka\u0142u\u017cna-Czapli\u0144ska","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"B24","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/0091-3057(80)90147-1","article-title":"Dietary tryptophan modulation and aggressive behavior in mice","volume":"12","author":"Kantak","year":"1980","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B25","first-page":"202","article-title":"Cloning of the gene for Na+\/serine-threonine symporter (sstT) from Haemophilus influenzae Rd and characteristics of the transporter","volume":"41","author":"Kim","year":"2003","journal-title":"J. Microbiol."},{"key":"B26","first-page":"78","article-title":"Characteristics of Na+-dependent serine transport in Haemophilus influenzae Rd","volume":"41","author":"Kim","year":"2003","journal-title":"J. Microbiol."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.21769\/bioprotoc.1781","article-title":"Extraction and quantification of tryptophan and kynurenine from cultured cells and media using a high performance liquid chromatography (HPLC) system equipped with an ultra-sensitive diode array detector","volume":"6","author":"Kim","year":"2016","journal-title":"Bio Protoc."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2023.11.836","article-title":"Transcriptome analysis of Edwardsiella piscicida during intracellular infection reveals excludons are involved with the activation of a mitochondrion-like energy generation program","volume":"15","author":"Lanza","year":"2024","journal-title":"mBio"},{"key":"B29","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1146\/annurev-pharmtox-052220-115707","article-title":"Aryl hydrocarbon receptor and its diverse ligands and functions: an exposome receptor","volume":"62","author":"Larigot","year":"2022","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1002\/eji.202149401","article-title":"Tryptophan and the innate intestinal immunity: Crosstalk between metabolites, host innate immune cells, and microbiota","volume":"52","author":"Li","year":"2022","journal-title":"Eur. J. Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1021\/acsinfecdis.9b00359","article-title":"Haemophilus influenzae glucose catabolism leading to production of the immunometabolite acetate has a key contribution to the host airway-pathogen interplay","volume":"6","author":"L\u00f3pez-L\u00f3pez","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2024.107586","article-title":"Chronic obstructive pulmonary disease and the airway microbiome: A review for clinicians","volume":"225","author":"Luo","year":"2024","journal-title":"Respir. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1080\/19490976.2020.1758008","article-title":"Host\u2013microbiome interactions: the aryl hydrocarbon receptor as a critical node in tryptophan metabolites to brain signaling","volume":"11","author":"Ma","year":"2020","journal-title":"Gut Microbes"},{"key":"B35","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1136\/thoraxjnl-2012-202127","article-title":"Decreased indoleamine 2,3-dioxygenase activity and IL-10\/IL-17A ratio in patients with COPD","volume":"68","author":"Maneechotesuwan","year":"2013","journal-title":"Thorax"},{"key":"B36","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1128\/jb.180.1.107-118.1998","article-title":"The tryptophanase gene cluster of Haemophilus influenzae Type b: evidence for horizontal gene transfer","volume":"180","author":"Martin","year":"1998","journal-title":"J. Bacteriol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1093\/intimm\/dxr072","article-title":"Aryl hydrocarbon receptor negatively regulates LPS-induced IL-6 production through suppression of histamine production in macrophages","volume":"23","author":"Masuda","year":"2011","journal-title":"Int. Immunol."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.617633","article-title":"Bacterial 3\u2032UTRs: A useful resource in post-transcriptional regulation","volume":"7","author":"Menendez-Gil","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3002","DOI":"10.1128\/iai.72.5.3002-3010.2004","article-title":"Partial analysis of the genomes of two nontypeable Haemophilus influenzae otitis media isolates","volume":"72","author":"Munson","year":"2004","journal-title":"Infect. Immun."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01571-17","article-title":"Whole-cell screen of fragment library identifies gut microbiota metabolite indole propionic acid as antitubercular","volume":"62","author":"Negatu","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02781-18","article-title":"Gut microbiota metabolite indole propionic acid targets tryptophan biosynthesis in Mycobacterium tuberculosis","volume":"10","author":"Negatu","year":"2019","journal-title":"mBio"},{"key":"B42","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1111\/1751-7915.13942","article-title":"Bacterial metabolism and pathogenesis intimate intertwining: time for metabolic modelling to come into action","volume":"15","author":"Nogales","year":"2022","journal-title":"Microb. Biotechnol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2014.00069","article-title":"Metabolic versatility in Haemophilus influenzae: A metabolomic and genomic analysis","volume":"5","author":"Othman","year":"2014","journal-title":"Front. Microbiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2723","DOI":"10.1128\/iai.00008-10","article-title":"Indoleamine 2,3-dioxygenase 1 is a lung-specific innate immune defense mechanism that inhibits growth of Francisella tularensis tryptophan auxotrophs","volume":"78","author":"Peng","year":"2010","journal-title":"Infect. Immun."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1128\/jb.97.3.1357-1361.1969","article-title":"Serine biosynthesis and regulation in Haemophilus influenzae","volume":"97","author":"Pizer","year":"1969","journal-title":"J. Bacteriol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/1601486","article-title":"Towards targeting the aryl hydrocarbon receptor in cystic fibrosis","volume":"2018","author":"Puccetti","year":"2018","journal-title":"Mediators Inflammation"},{"key":"B47","doi-asserted-by":"publisher","first-page":"2943","DOI":"10.1093\/bioinformatics\/btac166","article-title":"Analysing high-throughput sequencing data in Python with HTSeq 2.0","volume":"38","author":"Putri","year":"2022","journal-title":"Bioinformatics"},{"key":"B48","doi-asserted-by":"publisher","first-page":"W160","DOI":"10.1093\/nar\/gkw257","article-title":"deepTools2: a next generation web server for deep-sequencing data analysis","volume":"44","author":"Ram\u00edrez","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00993-23","article-title":"In vitro modeling of polyclonal infection dynamics within the human airways by Haemophilus influenzae differential fluorescent labeling","volume":"11","author":"Rap\u00fan-Araiz","year":"2023","journal-title":"Microbiol. Spectr"},{"key":"B50","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.ccm.2020.06.007","article-title":"Definition, causes, pathogenesis, and consequences of chronic obstructive pulmonary disease exacerbations","volume":"41","author":"Ritchie","year":"2020","journal-title":"Clinics Chest Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1080\/21505594.2021.1937883","article-title":"Development and multimodal characterization of an elastase-induced emphysema mouse disease model for the COPD frequent bacterial exacerbator phenotype","volume":"12","author":"Rodr\u00edguez-Arce","year":"2021","journal-title":"Virulence"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1038\/s41564-024-01661-6","article-title":"Bacteriophages avoid autoimmunity from cognate immune systems as an intrinsic part of their life cycles","volume":"9","author":"Rostol","year":"2024","journal-title":"Nat. Microbiol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1073\/pnas.1812746116","article-title":"Noncontiguous operon is a genetic organization for coordinating bacterial gene expression","volume":"116","author":"S\u00e1enz-Lahoya","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf686","article-title":"ExcludonFinder: mapping transcriptional overlaps between neighboring genes","volume":"53","author":"Sanmart\u00edn","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nrmicro2934","article-title":"The excludon: a new concept in bacterial antisense RNA-mediated gene regulation","volume":"11","author":"Sesto","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1080\/1040841x.2020.1863330","article-title":"Non-typeable Haemophilus influenzae chronic colonization in chronic obstructive pulmonary disease (COPD)","volume":"47","author":"Short","year":"2021","journal-title":"Crit. Rev. Microbiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1101\/gr.094607.109","article-title":"JBrowse: a next-generation genome browser","volume":"19","author":"Skinner","year":"2009","journal-title":"Genome Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"6021","DOI":"10.1073\/pnas.111150298","article-title":"The structures of anthranilate synthase of Serratia marcescens crystallized in the presence of (i) its substrates, chorismate and glutamine, and a product, glutamate, and (ii) its end-product inhibitor, l-tryptophan","volume":"98","author":"Spraggon","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B59","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1146\/annurev-immunol-032713-120245","article-title":"The aryl hydrocarbon receptor: multitasking in the immune system","volume":"32","author":"Stockinger","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02530","article-title":"The interplay between immune response and bacterial infection in COPD: focus upon non-typeable Haemophilus influenzae","volume":"9","author":"Su","year":"2018","journal-title":"Front. Immunol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1038\/nature08080","article-title":"The Listeria transcriptional landscape from saprophytism to virulence","volume":"459","author":"Toledo-Arana","year":"2009","journal-title":"Nature"},{"key":"B62","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1111\/mmi.14456","article-title":"Advances in bacterial transcriptome understanding: From overlapping transcription to the excludon concept","volume":"113","author":"Toledo-Arana","year":"2020","journal-title":"Mol. Microbiol."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-9-101","article-title":"Construction of non-polar mutants in Haemophilus influenzae using FLP recombinase technology","volume":"9","author":"Tracy","year":"2008","journal-title":"BMC Mol. Biol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"701","DOI":"10.3177\/jnsv.29.701","article-title":"Effects of dietary picolinate on mice deprived of tryptophan, niacin and vitamin B-6","volume":"29","author":"van Winkle","year":"1983","journal-title":"J. Nutr. Sci. Vitaminol (Tokyo)"},{"key":"B65","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/s0140-6736(07)61382-8","article-title":"COPD exacerbations: defining their cause and prevention","volume":"370","author":"Wedzicha","year":"2007","journal-title":"Lancet"},{"key":"B66","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1093\/jn\/105.5.550","article-title":"Comparison between the metabolic effects of tryptophan and histidine deficiencies in the rat","volume":"105","author":"Yokogoshi","year":"1975","journal-title":"J. Nutr."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1787089\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:25:54Z","timestamp":1783657554000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1787089\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":66,"alternative-id":["10.3389\/fcimb.2026.1787089"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1787089","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]},"article-number":"1787089"}}