{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:51:37Z","timestamp":1777596697748,"version":"3.51.4"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Programa Operacional Regional de Lisboa 2020","award":["LISBOA-01-0145-FEDER-007317"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-007317"]}]},{"DOI":"10.13039\/501100001871","name":"Ministry of Education and Science | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/QUI-BIQ\/118260\/2010"],"award-info":[{"award-number":["PTDC\/QUI-BIQ\/118260\/2010"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Ministry of Education and Science | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BPD\/86475\/2012"],"award-info":[{"award-number":["SFRH\/BPD\/86475\/2012"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Ministry of Education and Science | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/BIO\/04565\/2013"],"award-info":[{"award-number":["UID\/BIO\/04565\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            LysR-type transcriptional regulators (LTTRs) are the most commonly found regulators in\n            <jats:named-content content-type=\"genus-species\">Burkholderia cepacia<\/jats:named-content>\n            complex, comprising opportunistic pathogens causing chronic respiratory infections in cystic fibrosis (CF) patients. Despite LTTRs being global regulators of pathogenicity in several types of bacteria, few have been characterized in\n            <jats:named-content content-type=\"genus-species\">Burkholderia<\/jats:named-content>\n            . Here, we show that gene\n            <jats:italic>ldhR<\/jats:italic>\n            of\n            <jats:named-content content-type=\"genus-species\">B. multivorans<\/jats:named-content>\n            encoding an LTTR is cotranscribed with\n            <jats:italic>ldhA<\/jats:italic>\n            encoding a\n            <jats:sc>d<\/jats:sc>\n            -lactate dehydrogenase and evaluate their implication in virulence traits such as exopolysaccharide (EPS) synthesis and biofilm formation. A comparison of the wild type (WT) and its isogenic \u0394\n            <jats:italic>ldhR<\/jats:italic>\n            mutant grown in medium with 2%\n            <jats:sc>d<\/jats:sc>\n            -glucose revealed a negative impact on EPS biosynthesis and on cell viability in the presence of LdhR. The loss of viability in WT cells was caused by intracellular acidification as a consequence of the cumulative secretion of organic acids, including\n            <jats:sc>d<\/jats:sc>\n            -lactate, which was absent from the \u0394\n            <jats:italic>ldhR<\/jats:italic>\n            mutant supernatant. Furthermore, LdhR is implicated in the formation of planktonic cellular aggregates. WT cell aggregates reached 1,000 \u03bcm in size after 24 h in liquid cultures, in contrast to \u0394\n            <jats:italic>ldhR<\/jats:italic>\n            mutant aggregates that never grew more than 60 \u03bcm. The overexpression of\n            <jats:sc>d<\/jats:sc>\n            -lactate dehydrogenase LdhA in the \u0394\n            <jats:italic>ldhR<\/jats:italic>\n            mutant partially restored the formed aggregate size, suggesting a role for fermentation inside aggregates. Similar results were obtained for surface-attached biofilms, with WT cells producing more biofilm. A systematic evaluation of planktonic aggregates in\n            <jats:named-content content-type=\"genus-species\">Burkholderia<\/jats:named-content>\n            CF clinical isolates showed aggregates in 40 of 74. As CF patients' lung environments are microaerophilic and bacteria are found as free aggregates\/biofilms, LdhR and LdhA might have central roles in adapting to this environment.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Cystic fibrosis patients often suffer from chronic respiratory infections caused by several types of microorganisms. Among them are the\n            <jats:named-content content-type=\"genus-species\">Burkholderia cepacia<\/jats:named-content>\n            complex bacteria, which cause progressive deterioration of lung function that, in some patients, might develop into fatal necrotizing pneumoniae with bacteremia, known as \u201ccepacia syndrome.\u201d\n            <jats:named-content content-type=\"genus-species\">Burkholderia<\/jats:named-content>\n            pathogenesis is multifactorial as they express several virulence factors, form biofilms, and are highly resistant to antimicrobial compounds, making their eradication from the CF patients' airways very difficult. As\n            <jats:named-content content-type=\"genus-species\">Burkholderia<\/jats:named-content>\n            is commonly found in CF lungs in the form of cell aggregates and biofilms, the need to investigate the mechanisms of cellular aggregation is obvious. In this study, we demonstrate the importance of a\n            <jats:sc>d<\/jats:sc>\n            -lactate dehydrogenase and a regulator in regulating carbon overflow, cellular aggregates, and surface-attached biofilm formation. This not only enhances our understanding of\n            <jats:named-content content-type=\"genus-species\">Burkholderia<\/jats:named-content>\n            pathogenesis but can also lead to the development of drugs against these proteins to circumvent biofilm formation.\n          <\/jats:p>","DOI":"10.1128\/aem.01343-17","type":"journal-article","created":{"date-parts":[[2017,7,22]],"date-time":"2017-07-22T00:40:23Z","timestamp":1500684023000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Regulator LdhR and\n            <scp>d<\/scp>\n            -Lactate Dehydrogenase LdhA of Burkholderia multivorans Play Roles in Carbon Overflow and in Planktonic Cellular Aggregate Formation"],"prefix":"10.1128","volume":"83","author":[{"given":"In\u00eas N.","family":"Silva","sequence":"first","affiliation":[{"name":"IBB, Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico (IST), Lisbon, Portugal"}]},{"given":"Marcelo J.","family":"Ramires","sequence":"additional","affiliation":[{"name":"IBB, Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico (IST), Lisbon, Portugal"}]},{"given":"Lisa A.","family":"Azevedo","sequence":"additional","affiliation":[{"name":"IBB, Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico (IST), Lisbon, Portugal"}]},{"given":"Ana R.","family":"Guerreiro","sequence":"additional","affiliation":[{"name":"IBB, Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico (IST), Lisbon, Portugal"}]},{"given":"Andreia C.","family":"Tavares","sequence":"additional","affiliation":[{"name":"IBB, Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico (IST), Lisbon, Portugal"}]},{"given":"J\u00f6rg D.","family":"Becker","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6838-4245","authenticated-orcid":false,"given":"Leonilde M.","family":"Moreira","sequence":"additional","affiliation":[{"name":"IBB, Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico (IST), Lisbon, Portugal"},{"name":"Department of Bioengineering, IST, Universidade de Lisboa, Lisbon, Portugal"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00068-09"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01876-14"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1085"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-010-2528-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2011.00016"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02273-07"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01828-09"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.42.7.3052-3058.2004"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510692200"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/423141"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082522"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00998.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02091996"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01567339"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.10.118"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.050989-0"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12018"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0213870"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.075291-0"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005513"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1619529114"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp445"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.139.1.323-325.1979"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-008-0380-8"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-10-265"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/mbo3.24"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00591-09"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00237-16"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1207025110"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00694-15"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00029-16"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.997"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01450-06"},{"key":"e_1_3_3_35_2","volume-title":"Molecular cloning: a laboratory manual","author":"Sambrook J","year":"2001","unstructured":"Sambrook J RussellDW. 2001. Molecular cloning: a laboratory manual, 3rd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.","edition":"3"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2001-2-8-research0032"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.1.31"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.14.4476-4485.2004"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn524"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.22.4673"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/mst197"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1099\/00207713-47-4-1188"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.38.2.910-913.2000"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02713-14"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.6.2797-2798.2003"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.31.4.788-792.1993"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.52.2.383-384.1986"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(88)80018-0"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.4.1648"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.9.4443-4455.1999"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(91)90365-I"},{"key":"e_1_3_3_54_2","first-page":"800","article-title":"pBBR1MCS: a broad-host-range cloning vector","volume":"16","author":"Kovach ME","year":"1994","unstructured":"Kovach ME PhillipsRW ElzerPH RoopRM II PetersonKM. 1994. pBBR1MCS: a broad-host-range cloning vector. Biotechniques16:800\u2013802.","journal-title":"Biotechniques"}],"container-title":["Applied and Environmental Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AEM.01343-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AEM.01343-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T18:30:14Z","timestamp":1645641014000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AEM.01343-17"}},"subtitle":[],"editor":[{"given":"Ning-Yi","family":"Zhou","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2017,10]]},"references-count":53,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1128\/AEM.01343-17"],"URL":"https:\/\/doi.org\/10.1128\/aem.01343-17","relation":{},"ISSN":["0099-2240","1098-5336"],"issn-type":[{"value":"0099-2240","type":"print"},{"value":"1098-5336","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10]]},"assertion":[{"value":"2017-06-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-09-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01343-17"}}