{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:59:27Z","timestamp":1781632767874,"version":"3.54.5"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":31,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["20\/FFP-P\/8717"],"award-info":[{"award-number":["20\/FFP-P\/8717"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["20\/FFP-P\/8717"],"award-info":[{"award-number":["20\/FFP-P\/8717"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["20\/FFP-P\/8717"],"award-info":[{"award-number":["20\/FFP-P\/8717"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Irish Research Council"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Cystic fibrosis (CF) is characterised by chronic respiratory infections, involving opportunistic pathogens, including\n                      <jats:italic>Burkholderia cenocepacia<\/jats:italic>\n                      . The CF lung comprises hypoxic niches that drives bacterial adaptation, and the adaptability of pathogens to this environment is key to their successful colonisation. We previously identified several proteins encoded on a low-oxygen activated (Lxa) locus that were significantly increased in abundance in late chronic infection\n                      <jats:italic>B. cenocepacia<\/jats:italic>\n                      isolates. However, the impact of long-term hypoxia exposure on\n                      <jats:italic>B. cenocepacia<\/jats:italic>\n                      adaptation remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      To investigate the role of hypoxia in driving traits associated with chronic infection, we exposed an early infection\n                      <jats:italic>B. cenocepacia<\/jats:italic>\n                      isolate to low (6% O\u2082) or atmospheric oxygen (21% O\u2082) over 22 days. By day 22, 364 proteins were significantly increased in abundance in hypoxia-adapted cultures relative to the early infection isolate (Day 0). Overall, 1066 individual proteins were significantly increased in abundance in the hypoxia-adapted cultures relative to normoxia-adapted cultures, across four different timepoints from day 1 to day 22. Comparative proteome analysis identified 81 proteins with consistent changes in abundance both in hypoxia-adapted cultures and the respective late infection isolate relative to the early infection isolate, including\n                      <jats:italic>lxa<\/jats:italic>\n                      -encoded proteins and the FixK transcriptional regulator. Proteins associated with shikimate pathways were also significantly changed in abundance. Importantly, hypoxia-adapted cultures showed increased survival in CF macrophages, increased attachment to CF lung cells, elevated protease activity, greater resistance to ceftazidime and ciprofloxacin, all of which are consistent with adaptations observed in late chronic infection isolates. Hypoxia-adapted cultures also displayed enhanced virulence in\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      larvae, as did the late infection isolate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The changes in phenotype and proteome of\n                      <jats:italic>B. cenocepacia<\/jats:italic>\n                      observed after long-term hypoxia suggest that hypoxia may drive the adaptation to chronic infection, promoting survival in macrophages, host-cell attachment, antibiotic resistance and protease activity. Therapeutic strategies that modulate oxygen availability or target hypoxia-sensing may hold promise in preventing or mitigating chronic infection in CF.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12866-026-04781-7","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T04:52:32Z","timestamp":1770353552000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adaptation of Burkholderia cenocepacia to low oxygen drives changes consistent with adaptation to chronic infection"],"prefix":"10.1186","volume":"26","author":[{"given":"Ciar\u00e1n J.","family":"Carey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Drabinska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh","family":"Duggan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobh\u00e1n","family":"McClean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"4781_CR1","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.biocel.2014.02.023","volume":"52","author":"P Fanen","year":"2014","unstructured":"Fanen P, Wohlhuter-Haddad A, Hinzpeter A. Genetics of cystic fibrosis: CFTR mutation classifications toward genotype-based CF therapies. Int J Biochem Cell Biol. 2014;52:94\u2013102. https:\/\/doi.org\/10.1016\/j.biocel.2014.02.023.","journal-title":"Int J Biochem Cell Biol"},{"issue":"Suppl 1","key":"4781_CR2","doi-asserted-by":"publisher","first-page":"S125","DOI":"10.3109\/13693786.2010.521522","volume":"48","author":"LW Leclair","year":"2010","unstructured":"Leclair LW, Hogan DA. Mixed bacterial-fungal infections in the CF respiratory tract. Med Mycol. 2010;48(Suppl 1):S125\u201332. https:\/\/doi.org\/10.3109\/13693786.2010.521522.","journal-title":"Med Mycol"},{"issue":"Supplement2","key":"4781_CR3","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1093\/jpids\/piac052","volume":"11","author":"AC Blanchard","year":"2022","unstructured":"Blanchard AC, Waters VJ. Opportunistic pathogens in cystic fibrosis: epidemiology and pathogenesis of lung infection. J Pediatr Infect Dis Soc. 2022;11(Supplement2):S3\u201312. https:\/\/doi.org\/10.1093\/jpids\/piac052.","journal-title":"J Pediatr Infect Dis Soc"},{"issue":"6","key":"4781_CR4","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.ijmm.2010.04.010","volume":"300","author":"U Dobrindt","year":"2010","unstructured":"Dobrindt U, Zdziarski J, Salvador E, Hacker J. Bacterial genome plasticity and its impact on adaptation during persistent infection. Int J Med Microbiol. 2010;300(6):363\u20136. https:\/\/doi.org\/10.1016\/j.ijmm.2010.04.010.","journal-title":"Int J Med Microbiol"},{"key":"4781_CR5","doi-asserted-by":"publisher","unstructured":"Dawan J, Ahn J. Bacterial stress responses as potential targets in overcoming antibiotic resistance. Microorganisms. 2022;10(7). https:\/\/doi.org\/10.3390\/microorganisms10071385.","DOI":"10.3390\/microorganisms10071385"},{"issue":"9","key":"4781_CR6","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1093\/jac\/dks196","volume":"67","author":"K Poole","year":"2012","unstructured":"Poole K. Bacterial stress responses as determinants of antimicrobial resistance. J Antimicrob Chemother. 2012;67(9):2069\u201389. https:\/\/doi.org\/10.1093\/jac\/dks196.","journal-title":"J Antimicrob Chemother"},{"key":"4781_CR7","doi-asserted-by":"publisher","unstructured":"Carey CJ, Duggan N, Drabinska J, McClean S. Harnessing hypoxia: bacterial adaptation and chronic infection in cystic fibrosis. FEMS Microbiol Rev. 2025;49. https:\/\/doi.org\/10.1093\/femsre\/fuaf018.","DOI":"10.1093\/femsre\/fuaf018"},{"key":"4781_CR8","doi-asserted-by":"publisher","unstructured":"Jurado-Martin I, Sainz-Mejias M, McClean S. Pseudomonas aeruginosa: an audacious pathogen with an adaptable arsenal of virulence factors. Int J Mol Sci. 2021;22(6). https:\/\/doi.org\/10.3390\/ijms22063128.","DOI":"10.3390\/ijms22063128"},{"issue":"3","key":"4781_CR9","doi-asserted-by":"publisher","first-page":"126415","DOI":"10.1016\/j.syapm.2023.126415","volume":"46","author":"LS Velez","year":"2023","unstructured":"Velez LS, Aburjaile FF, Farias ARG, Baia ADB, Oliveira WJ, Silva AMF, et al. Burkholderia semiarida sp. nov. And burkholderia Sola sp. nov., two novel B. cepacia complex species causing onion sour skin. Syst Appl Microbiol. 2023;46(3):126415. https:\/\/doi.org\/10.1016\/j.syapm.2023.126415.","journal-title":"Syst Appl Microbiol"},{"issue":"7","key":"4781_CR10","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1111\/j.1469-0691.2010.03237.x","volume":"16","author":"P Drevinek","year":"2010","unstructured":"Drevinek P, Mahenthiralingam E. Burkholderia cenocepacia in cystic fibrosis: epidemiology and molecular mechanisms of virulence. Clin Microbiol Infect. 2010;16(7):821\u201330. https:\/\/doi.org\/10.1111\/j.1469-0691.2010.03237.x.","journal-title":"Clin Microbiol Infect"},{"key":"4781_CR11","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.3389\/fmicb.2017.01592","volume":"8","author":"VC Scoffone","year":"2017","unstructured":"Scoffone VC, Chiarelli LR, Trespidi G, Mentasti M, Riccardi G, Buroni S. Burkholderia cenocepacia infections in cystic fibrosis patients: drug resistance and therapeutic approaches. Front Microbiol. 2017;8:1592. https:\/\/doi.org\/10.3389\/fmicb.2017.01592.","journal-title":"Front Microbiol"},{"key":"4781_CR12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3389\/fcimb.2011.00015","volume":"1","author":"EP O\u2019Grady","year":"2011","unstructured":"O\u2019Grady EP, Sokol PA. Burkholderia cenocepacia differential gene expression during host-pathogen interactions and adaptation to the host environment. Front Cell Infect Microbiol. 2011;1:15. https:\/\/doi.org\/10.3389\/fcimb.2011.00015.","journal-title":"Front Cell Infect Microbiol"},{"issue":"2","key":"4781_CR13","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/nrmicro1085","volume":"3","author":"E Mahenthiralingam","year":"2005","unstructured":"Mahenthiralingam E, Urban TA, Goldberg JB. The multifarious, multireplicon burkholderia Cepacia complex. Nat Rev Microbiol. 2005;3(2):144\u201356.","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"4781_CR14","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.jcf.2004.01.005","volume":"3","author":"JM Courtney","year":"2004","unstructured":"Courtney JM, Dunbar KE, McDowell A, Moore JE, Warke TJ, Stevenson M, et al. Clinical outcome of burkholderia Cepacia complex infection in cystic fibrosis adults. J Cyst Fibros. 2004;3(2):93\u20138.","journal-title":"J Cyst Fibros"},{"issue":"2","key":"4781_CR15","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.jcf.2004.03.007","volume":"3","author":"L Blackburn","year":"2004","unstructured":"Blackburn L, Brownlee K, Conway S, Denton M. Cepacia syndrome\u2019 with burkholderia multivorans, 9 years after initial colonization. J Cyst Fibros. 2004;3(2):133\u20134.","journal-title":"J Cyst Fibros"},{"key":"4781_CR16","doi-asserted-by":"publisher","first-page":"102262","DOI":"10.1016\/j.coph.2022.102262","volume":"65","author":"MA Greenwald","year":"2022","unstructured":"Greenwald MA, Wolfgang MC. The changing landscape of the cystic fibrosis lung environment: from the perspective of Pseudomonas aeruginosa. Curr Opin Pharmacol. 2022;65:102262. https:\/\/doi.org\/10.1016\/j.coph.2022.102262.","journal-title":"Curr Opin Pharmacol"},{"issue":"7","key":"4781_CR17","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.tim.2022.01.002","volume":"30","author":"AC Andr\u00e9","year":"2022","unstructured":"Andr\u00e9 AC, Laborde M, Marteyn BS. The battle for oxygen during bacterial and fungal infections. Trends Microbiol. 2022;30(7):643\u201353. https:\/\/doi.org\/10.1016\/j.tim.2022.01.002.","journal-title":"Trends Microbiol"},{"issue":"12","key":"4781_CR18","doi-asserted-by":"publisher","first-page":"e1005258","DOI":"10.1371\/journal.ppat.1005258","volume":"11","author":"LM Filkins","year":"2015","unstructured":"Filkins LM, O\u2019Toole GA. Cystic fibrosis lung infections: Polymicrobial, Complex, and hard to treat. PLoS Pathog. 2015;11(12):e1005258. https:\/\/doi.org\/10.1371\/journal.ppat.1005258.","journal-title":"PLoS Pathog"},{"issue":"8","key":"4781_CR19","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1038\/ismej.2013.36","volume":"7","author":"AM Sass","year":"2013","unstructured":"Sass AM, Schmerk C, Agnoli K, Norville PJ, Eberl L, Valvano MA, et al. The unexpected discovery of a novel low-oxygen-activated locus for the anoxic persistence of burkholderia cenocepacia. Isme J. 2013;7(8):1568\u201381. https:\/\/doi.org\/10.1038\/ismej.2013.36.","journal-title":"Isme J"},{"issue":"1","key":"4781_CR20","doi-asserted-by":"publisher","first-page":"13386","DOI":"10.1038\/s41598-018-31556-6","volume":"8","author":"L Cullen","year":"2018","unstructured":"Cullen L, O\u2019Connor A, McCormack S, Owens RA, Holt GS, Collins C, et al. The involvement of the low-oxygen-activated locus of burkholderia cenocepacia in adaptation during cystic fibrosis infection. Sci Rep. 2018;8(1):13386. https:\/\/doi.org\/10.1038\/s41598-018-31556-6.","journal-title":"Sci Rep"},{"issue":"1","key":"4781_CR21","doi-asserted-by":"publisher","first-page":"e1311","DOI":"10.1002\/mbo3.1311","volume":"12","author":"A O\u2019Connor","year":"2023","unstructured":"O\u2019Connor A, Jurado-Martin I, Mysior MM, Manzira AL, Drabinska J, Simpson JC, et al. A universal stress protein upregulated by hypoxia has a role in burkholderia cenocepacia intramacrophage survival: implications for chronic infection in cystic fibrosis. Microbiologyopen. 2023;12(1):e1311. https:\/\/doi.org\/10.1002\/mbo3.1311.","journal-title":"Microbiologyopen"},{"issue":"6","key":"4781_CR22","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1164\/rccm.201607-1360LE","volume":"195","author":"L Cullen","year":"2017","unstructured":"Cullen L, O\u2019Connor A, Drevinek P, Schaffer K, McClean S. Sequential burkholderia cenocepacia isolates from siblings with cystic fibrosis show increased lung cell attachment. Am J Respir Crit Care Med. 2017;195(6):832\u20135. https:\/\/doi.org\/10.1164\/rccm.201607-1360LE.","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"4781_CR23","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.tim.2023.06.010","volume":"32","author":"A Tikhomirova","year":"2024","unstructured":"Tikhomirova A, Rahman MM, Kidd SP, Ferrero RL, Roujeinikova A. Cysteine and resistance to oxidative stress: implications for virulence and antibiotic resistance. Trends Microbiol. 2024;32(1):93\u2013104. https:\/\/doi.org\/10.1016\/j.tim.2023.06.010.","journal-title":"Trends Microbiol"},{"issue":"Pt 1","key":"4781_CR24","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1099\/mic.0.2006\/000455-0","volume":"153","author":"JW Chung","year":"2007","unstructured":"Chung JW, Speert DP. Proteomic identification and characterization of bacterial factors associated with burkholderia cenocepacia survival in a murine host. Microbiol (Reading). 2007;153(Pt 1):206\u201314. https:\/\/doi.org\/10.1099\/mic.0.2006\/000455-0.","journal-title":"Microbiol (Reading)"},{"key":"4781_CR25","doi-asserted-by":"publisher","first-page":"102936","DOI":"10.1016\/j.redox.2023.102936","volume":"67","author":"JN Cobley","year":"2023","unstructured":"Cobley JN. 50 shades of oxidative stress: A state-specific cysteine redox pattern hypothesis. Redox Biol. 2023;67:102936. https:\/\/doi.org\/10.1016\/j.redox.2023.102936.","journal-title":"Redox Biol"},{"issue":"11","key":"4781_CR26","doi-asserted-by":"publisher","first-page":"4729","DOI":"10.1128\/IAI.01876-14","volume":"82","author":"U Schwab","year":"2014","unstructured":"Schwab U, Abdullah LH, Perlmutt OS, Albert D, Davis CW, Arnold RR, et al. Localization of burkholderia Cepacia complex bacteria in cystic fibrosis lungs and interactions with Pseudomonas aeruginosa in hypoxic mucus. Infect Immun. 2014;82(11):4729\u201345. https:\/\/doi.org\/10.1128\/IAI.01876-14.","journal-title":"Infect Immun"},{"issue":"5","key":"4781_CR27","doi-asserted-by":"publisher","first-page":"427","DOI":"10.4161\/viru.2.5.17711","volume":"2","author":"M Kawada-Matsuo","year":"2011","unstructured":"Kawada-Matsuo M, Yoshida Y, Nakamura N, Komatsuzawa H. Role of two-component systems in the resistance of Staphylococcus aureus to antibacterial agents. Virulence. 2011;2(5):427\u201330. https:\/\/doi.org\/10.4161\/viru.2.5.17711.","journal-title":"Virulence"},{"issue":"51","key":"4781_CR28","doi-asserted-by":"publisher","first-page":"7011","DOI":"10.1021\/acs.biochem.8b00946","volume":"57","author":"MP Czub","year":"2018","unstructured":"Czub MP, Zhang B, Chiarelli MP, Majorek KA, Joe L, Porebski PJ, et al. A Gcn5-Related N-Acetyltransferase (GNAT) capable of acetylating polymyxin B and colistin antibiotics in vitro. Biochemistry. 2018;57(51):7011\u201320. https:\/\/doi.org\/10.1021\/acs.biochem.8b00946.","journal-title":"Biochemistry"},{"key":"4781_CR29","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1146\/annurev-micro-042621-122343","volume":"75","author":"G Bange","year":"2021","unstructured":"Bange G, Brodersen DE, Liuzzi A, Steinchen W. Two P or not two P: Understanding regulation by the bacterial second messengers (p)ppGpp. Annu Rev Microbiol. 2021;75:383\u2013406. https:\/\/doi.org\/10.1146\/annurev-micro-042621-122343.","journal-title":"Annu Rev Microbiol"},{"key":"4781_CR30","doi-asserted-by":"publisher","first-page":"107331","DOI":"10.1016\/j.micpath.2025.107331","volume":"200","author":"J Che","year":"2025","unstructured":"Che J, Liu B, Fang Q, Nissa MU, Luo T, Wang L, et al. Biological studies reveal the role of TrpA gene in biofilm formation, motility, hemolysis and virulence in vibrio anguillarum. Microb Pathog. 2025;200:107331. https:\/\/doi.org\/10.1016\/j.micpath.2025.107331.","journal-title":"Microb Pathog"},{"key":"4781_CR31","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1146\/annurev.arplant.50.1.473","volume":"50","author":"KM Herrmann","year":"1999","unstructured":"Herrmann KM, Weaver LM. The shikimate pathway. Annu Rev Plant Physiol Plant Mol Biol. 1999;50:473\u2013503. https:\/\/doi.org\/10.1146\/annurev.arplant.50.1.473.","journal-title":"Annu Rev Plant Physiol Plant Mol Biol"},{"key":"4781_CR32","doi-asserted-by":"publisher","unstructured":"Lightly TJ, Frejuk KL, Groleau MC, Chiarelli LR, Ras C, Buroni S, et al. Phenylacetyl coenzyme A, not phenylacetic Acid, attenuates CepIR-Regulated virulence in burkholderia cenocepacia. Appl Environ Microbiol. 2019;85(24). https:\/\/doi.org\/10.1128\/aem.01594-19.","DOI":"10.1128\/aem.01594-19"},{"key":"4781_CR33","doi-asserted-by":"publisher","unstructured":"Tavares M, Kozak M, Balola A, S\u00e1-Correia I. Burkholderia Cepacia complex bacteria: a feared contamination risk in Water-Based pharmaceutical products. Clin Microbiol Rev. 2020;33(3). https:\/\/doi.org\/10.1128\/cmr.00139-19.","DOI":"10.1128\/cmr.00139-19"},{"key":"4781_CR34","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jinorgbio.2013.12.010","volume":"133","author":"CY Taabazuing","year":"2014","unstructured":"Taabazuing CY, Hangasky JA, Knapp MJ. Oxygen sensing strategies in mammals and bacteria. J Inorg Biochem. 2014;133:63\u201372. https:\/\/doi.org\/10.1016\/j.jinorgbio.2013.12.010.","journal-title":"J Inorg Biochem"},{"issue":"1","key":"4781_CR35","doi-asserted-by":"publisher","first-page":"e1006116","DOI":"10.1371\/journal.ppat.1006116","volume":"13","author":"MM Schaefers","year":"2017","unstructured":"Schaefers MM, Liao TL, Boisvert NM, Roux D, Yoder-Himes D, Priebe GP. An Oxygen-Sensing Two-Component system in the burkholderia Cepacia complex regulates Biofilm, intracellular Invasion, and pathogenicity. PLoS Pathog. 2017;13(1):e1006116. https:\/\/doi.org\/10.1371\/journal.ppat.1006116.","journal-title":"PLoS Pathog"},{"issue":"3","key":"4781_CR36","doi-asserted-by":"publisher","first-page":"031501","DOI":"10.1063\/1.4953660","volume":"10","author":"JP Shen","year":"2016","unstructured":"Shen JP, Chou CF. Morphological plasticity of bacteria-Open questions. Biomicrofluidics. 2016;10(3):031501. https:\/\/doi.org\/10.1063\/1.4953660.","journal-title":"Biomicrofluidics"},{"issue":"11","key":"4781_CR37","doi-asserted-by":"publisher","first-page":"3492","DOI":"10.1128\/JB.00119-09","volume":"191","author":"M Starkey","year":"2009","unstructured":"Starkey M, Hickman JH, Ma L, Zhang N, De Long S, Hinz A, et al. Pseudomonas aeruginosa rugose small-colony variants have adaptations that likely promote persistence in the cystic fibrosis lung. J Bacteriol. 2009;191(11):3492\u2013503. https:\/\/doi.org\/10.1128\/JB.00119-09.","journal-title":"J Bacteriol"},{"key":"4781_CR38","doi-asserted-by":"publisher","first-page":"590","DOI":"10.3389\/fmicb.2020.00590","volume":"11","author":"J Ho\u0142\u00f3wka","year":"2020","unstructured":"Ho\u0142\u00f3wka J, Zakrzewska-Czerwi\u0144ska J. Nucleoid associated proteins: the small organizers that help to Cope with stress. Front Microbiol. 2020;11:590. https:\/\/doi.org\/10.3389\/fmicb.2020.00590.","journal-title":"Front Microbiol"},{"key":"4781_CR39","doi-asserted-by":"publisher","unstructured":"Trastoy R, Manso T, Fern\u00e1ndez-Garc\u00eda L, Blasco L, Ambroa A, Del P\u00e9rez ML, et al. Mechanisms of bacterial tolerance and persistence in the Gastrointestinal and respiratory environments. Clin Microbiol Rev. 2018;31(4). https:\/\/doi.org\/10.1128\/cmr.00023-18.","DOI":"10.1128\/cmr.00023-18"},{"issue":"1","key":"4781_CR40","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1309\/kjrpc7dd5tr9ntdm","volume":"128","author":"B Pritt","year":"2007","unstructured":"Pritt B, O\u2019Brien L, Winn W. Mucoid Pseudomonas in cystic fibrosis. Am J Clin Pathol. 2007;128(1):32\u20134. https:\/\/doi.org\/10.1309\/kjrpc7dd5tr9ntdm.","journal-title":"Am J Clin Pathol"},{"issue":"12","key":"4781_CR41","doi-asserted-by":"publisher","first-page":"e52330","DOI":"10.1371\/journal.pone.0052330","volume":"7","author":"A Bragonzi","year":"2012","unstructured":"Bragonzi A, Farulla I, Paroni M, Twomey KB, Pirone L, Lor\u00e8 NI, et al. Modelling co-infection of the cystic fibrosis lung by Pseudomonas aeruginosa and burkholderia cenocepacia reveals influences on biofilm formation and host response. PLoS ONE. 2012;7(12):e52330. https:\/\/doi.org\/10.1371\/journal.pone.0052330.","journal-title":"PLoS ONE"},{"issue":"6","key":"4781_CR42","doi-asserted-by":"publisher","first-page":"e1006437","DOI":"10.1371\/journal.ppat.1006437","volume":"13","author":"J Mesureur","year":"2017","unstructured":"Mesureur J, Feliciano JR, Wagner N, Gomes MC, Zhang L, Blanco-Gonzalez M, et al. Macrophages, but not neutrophils, are critical for proliferation of burkholderia cenocepacia and ensuing host-damaging inflammation. PLoS Pathog. 2017;13(6):e1006437. https:\/\/doi.org\/10.1371\/journal.ppat.1006437.","journal-title":"PLoS Pathog"},{"issue":"4","key":"4781_CR43","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1128\/aac.00007-13","volume":"57","author":"KS Brandenburg","year":"2013","unstructured":"Brandenburg KS, Rodriguez KJ, McAnulty JF, Murphy CJ, Abbott NL, Schurr MJ, et al. Tryptophan inhibits biofilm formation by Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2013;57(4):1921\u20135. https:\/\/doi.org\/10.1128\/aac.00007-13.","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"4781_CR44","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1128\/IAI.00768-12","volume":"81","author":"S Schwager","year":"2013","unstructured":"Schwager S, Agnoli K, Kothe M, Feldmann F, Givskov M, Carlier A, et al. Identification of burkholderia cenocepacia strain H111 virulence factors using nonmammalian infection hosts. Infect Immun. 2013;81(1):143\u201353. https:\/\/doi.org\/10.1128\/IAI.00768-12.","journal-title":"Infect Immun"},{"issue":"3","key":"4781_CR45","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/mmi.12771","volume":"94","author":"T Pribytkova","year":"2014","unstructured":"Pribytkova T, Lightly TJ, Kumar B, Bernier SP, Sorensen JL, Surette MG, et al. The attenuated virulence of a burkholderia cenocepacia PaaABCDE mutant is due to Inhibition of quorum sensing by release of phenylacetic acid. Mol Microbiol. 2014;94(3):522\u201336. https:\/\/doi.org\/10.1111\/mmi.12771.","journal-title":"Mol Microbiol"},{"issue":"2","key":"4781_CR46","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/s0378-1097(03)00785-7","volume":"228","author":"M Tomich","year":"2003","unstructured":"Tomich M, Mohr CD. Adherence and autoaggregation phenotypes of a burkholderia cenocepacia cable Pilus mutant. FEMS Microbiol Lett. 2003;228(2):287\u201397. https:\/\/doi.org\/10.1016\/s0378-1097(03)00785-7.","journal-title":"FEMS Microbiol Lett"},{"issue":"10","key":"4781_CR47","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1093\/glycob\/cws105","volume":"22","author":"R Marchetti","year":"2012","unstructured":"Marchetti R, Malinovska L, Lameign\u00e8re E, Adamova L, de Castro C, Cioci G, et al. Burkholderia cenocepacia lectin A binding to heptoses from the bacterial lipopolysaccharide. Glycobiology. 2012;22(10):1387\u201398. https:\/\/doi.org\/10.1093\/glycob\/cws105.","journal-title":"Glycobiology"},{"issue":"13","key":"4781_CR48","doi-asserted-by":"publisher","first-page":"4421","DOI":"10.1128\/JB.187.13.4421-4429.2005","volume":"187","author":"C Kooi","year":"2005","unstructured":"Kooi C, Corbett CR, Sokol PA. Functional analysis of the burkholderia cenocepacia ZmpA metalloprotease. J Bacteriol. 2005;187(13):4421\u20139.","journal-title":"J Bacteriol"},{"issue":"5","key":"4781_CR49","doi-asserted-by":"publisher","first-page":"e1012214","DOI":"10.1371\/journal.ppat.1012214","volume":"20","author":"X Zang","year":"2024","unstructured":"Zang X, Zhang J, Jiang Y, Feng T, Cui Y, Wang H, et al. Serine protease Rv2569c facilitates transmission of Mycobacterium tuberculosis via disrupting the epithelial barrier by cleaving E-cadherin. PLoS Pathog. 2024;20(5):e1012214. https:\/\/doi.org\/10.1371\/journal.ppat.1012214.","journal-title":"PLoS Pathog"},{"issue":"6","key":"4781_CR50","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1111\/mmi.14685","volume":"115","author":"B Zellner","year":"2021","unstructured":"Zellner B, Mengin-Lecreulx D, Tully B, Gunning WT 3rd, Booth R, Huntley JF. A Francisella tularensis L,D-carboxypeptidase plays important roles in cell morphology, envelope integrity, and virulence. Mol Microbiol. 2021;115(6):1357\u201378. https:\/\/doi.org\/10.1111\/mmi.14685.","journal-title":"Mol Microbiol"},{"issue":"21","key":"4781_CR51","doi-asserted-by":"publisher","first-page":"e0025021","DOI":"10.1128\/JB.00250-21","volume":"203","author":"RL Neve","year":"2021","unstructured":"Neve RL, Carrillo BD, Phelan VV. Impact of artificial sputum medium formulation on Pseudomonas aeruginosa secondary metabolite production. J Bacteriol. 2021;203(21):e0025021. https:\/\/doi.org\/10.1128\/JB.00250-21.","journal-title":"J Bacteriol"},{"key":"4781_CR52","doi-asserted-by":"publisher","unstructured":"Moliteo E, Sciacca M, Palmeri A, Papale M, Manti S, Parisi GF, et al. Cystic fibrosis and oxidative stress: the role of CFTR. Molecules. 2022;27(16). https:\/\/doi.org\/10.3390\/molecules27165324.","DOI":"10.3390\/molecules27165324"},{"key":"4781_CR53","doi-asserted-by":"publisher","DOI":"10.1101\/2023.12.02.569726","author":"KE Mansour","year":"2023","unstructured":"Mansour KE, Qi Y, Yan M, Ramstrom O, Priebe GP, Schaefers MM. Small-molecule activators of a bacterial signaling pathway inhibit virulence. BioRxiv. 2023. https:\/\/doi.org\/10.1101\/2023.12.02.569726.","journal-title":"BioRxiv"},{"issue":"22","key":"4781_CR54","doi-asserted-by":"publisher","first-page":"7866","DOI":"10.1128\/jb.187.22.7866-7869.2005","volume":"187","author":"KL Colabroy","year":"2005","unstructured":"Colabroy KL, Begley TP. Tryptophan catabolism: identification and characterization of a new degradative pathway. J Bacteriol. 2005;187(22):7866\u20139. https:\/\/doi.org\/10.1128\/jb.187.22.7866-7869.2005.","journal-title":"J Bacteriol"},{"issue":"3","key":"4781_CR55","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1111\/j.1365-2958.2004.04029.x","volume":"52","author":"H Wood","year":"2004","unstructured":"Wood H, Roshick C, McClarty G. Tryptophan recycling is responsible for the interferon-gamma resistance of chlamydia psittaci GPIC in indoleamine dioxygenase-expressing host cells. Mol Microbiol. 2004;52(3):903\u201316. https:\/\/doi.org\/10.1111\/j.1365-2958.2004.04029.x.","journal-title":"Mol Microbiol"}],"container-title":["BMC Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12866-026-04781-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-026-04781-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-026-04781-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:38:22Z","timestamp":1781631502000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12866-026-04781-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4781"],"URL":"https:\/\/doi.org\/10.1186\/s12866-026-04781-7","relation":{},"ISSN":["1471-2180"],"issn-type":[{"value":"1471-2180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]},"assertion":[{"value":"23 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Full ethical approval granted for use of CF patient PBMCs on 4th April 2018 from the St Vincent\u2019s University Hospital Research Ethics committee. The study adhered to the principles and rules of the Declaration of Helsinki. All participants were informed of the study, and written consent was obtained prior to blood sampling.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"212"}}