{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T06:48:31Z","timestamp":1782802111764,"version":"3.54.5"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"publisher","award":["31900115"],"award-info":[{"award-number":["31900115"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Pseudomonas aeruginosa can utilize abundant phosphatidylcholine (PC) and phosphatidylethanolamine (PE) within the host as energy and structural substrates. Fatty acids, choline, and ethanolamine liberated from PC and PE can each serve as the sole carbon source to support bacterial growth in vitro. Our previous work demonstrated that fatty acid metabolism is critical for acute pulmonary infection caused by P. aeruginosa. The pathogen senses host-derived fatty acids via the transcriptional regulator PvrA, which activates fatty acid utilization pathways and drives the production of virulence factors required for acute infection. In this study, we demonstrate that during acute pulmonary infection in mice, P. aeruginosa upregulates fatty acid catabolism while simultaneously repressing choline and ethanolamine uptake and metabolism pathways. Deletion of the transcriptional activators GbdR and EatR (which control choline and ethanolamine utilization respectively) enhances pulmonary bacterial colonization. We further identify fatty acids as environmental signals that trigger repression of choline and ethanolamine utilization programs. PvrA mediates this signaling cascade by directly binding to the promoters of gbdR and eatR and suppressing their transcription upon fatty acid exposure.<\/jats:p>","DOI":"10.3390\/pathogens15070680","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:58:04Z","timestamp":1782799084000},"page":"680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PvrA-Mediated Inhibition of Choline and Ethanolamine Uptake Promotes Pseudomonas aeruginosa Colonization in the Host Environment"],"prefix":"10.3390","volume":"15","author":[{"given":"Shuo","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Yin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7533-0598","authenticated-orcid":false,"given":"Jinhao","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changru","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China"},{"name":"State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0140-6736(01)05714-2","article-title":"Spread of a multiresistant strain of Pseudomonas aeruginosa in an adult cystic fibrosis clinic","volume":"358","author":"Jones","year":"2001","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1164\/rccm.200204-269OC","article-title":"Detection of a widespread clone of Pseudomonas aeruginosa in a pediatric cystic fibrosis clinic","volume":"166","author":"Armstrong","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1111\/resp.13544","article-title":"Transmission of bacteria in bronchiectasis and chronic obstructive pulmonary disease: Low burden of cough aerosols","volume":"24","author":"Stockwell","year":"2019","journal-title":"Respirology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1164\/rccm.201705-1043SO","article-title":"Mechanisms and Targeted Therapies for Pseudomonas aeruginosa Lung Infection","volume":"197","author":"Curran","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e0178825","DOI":"10.1128\/mbio.01788-25","article-title":"Pseudomonas aeruginosa lasR-deficient mutant contributes to bacterial virulence through enhancing the PhoB-mediated pathway in response to host environment","volume":"16","author":"Pan","year":"2025","journal-title":"mBio"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gks1039","article-title":"A dynamic and intricate regulatory network determines Pseudomonas aeruginosa virulence","volume":"41","author":"Balasubramanian","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.biotechadv.2018.11.013","article-title":"Antibiotic resistance in Pseudomonas aeruginosa: Mechanisms and alternative therapeutic strategies","volume":"37","author":"Pang","year":"2019","journal-title":"Biotechnol. Adv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5313","DOI":"10.1128\/IAI.01807-06","article-title":"In vivo evidence of Pseudomonas aeruginosa nutrient acquisition and pathogenesis in the lungs of cystic fibrosis patients","volume":"75","author":"Son","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sun, Z., Kang, Y., Norris, M.H., Troyer, R.M., Son, M.S., Schweizer, H.P., Dow, S.W., and Hoang, T.T. (2014). Blocking phosphatidylcholine utilization in Pseudomonas aeruginosa, via mutagenesis of fatty acid, glycerol and choline degradation pathways, confirms the importance of this nutrient source in vivo. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103778"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4038","DOI":"10.1128\/JB.00129-08","article-title":"Pseudomonas aeruginosa twitching motility-mediated chemotaxis towards phospholipids and fatty acids: Specificity and metabolic requirements","volume":"190","author":"Miller","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1111\/j.1365-2958.2007.05947.x","article-title":"Regulation of fatty acid metabolism in bacteria","volume":"66","author":"Fujita","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/j.chembiol.2013.09.021","article-title":"The end of an old hypothesis: The pseudomonas signaling molecules 4-hydroxy-2-alkylquinolines derive from fatty acids, not 3-ketofatty acids","volume":"20","author":"Dulcey","year":"2013","journal-title":"Chem. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1002\/cbic.201800153","article-title":"The Alkylquinolone Repertoire of Pseudomonas aeruginosa is Linked to Structural Flexibility of the FabH-like 2-Heptyl-3-hydroxy-4(1H)-quinolone (PQS) Biosynthesis Enzyme PqsBC","volume":"19","author":"Witzgall","year":"2018","journal-title":"Chembiochem"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8611","DOI":"10.1128\/AEM.02111-12","article-title":"Fatty acid cosubstrates provide \u03b2-oxidation precursors for rhamnolipid biosynthesis in Pseudomonas aeruginosa, as evidenced by isotope tracing and gene expression assays","volume":"78","author":"Zhang","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1099\/mic.0.2008\/018135-0","article-title":"The Pseudomonas aeruginosa PsrA responds to long-chain fatty acid signals to regulate the fadBA5 beta-oxidation operon","volume":"154","author":"Kang","year":"2008","journal-title":"Microbiology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5967","DOI":"10.1093\/nar\/gkaa377","article-title":"PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids","volume":"48","author":"Pan","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/j.1365-2958.2006.05088.x","article-title":"Two aerobic pathways for the formation of unsaturated fatty acids in Pseudomonas aeruginosa","volume":"60","author":"Zhu","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e0078623","DOI":"10.1128\/msphere.00786-23","article-title":"Glycerol metabolism impacts biofilm phenotypes and virulence in Pseudomonas aeruginosa via the Entner-Doudoroff pathway","volume":"9","author":"Pan","year":"2024","journal-title":"mSphere"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e02079-19","DOI":"10.1128\/mBio.02079-19","article-title":"TpiA is a Key Metabolic Enzyme That Affects Virulence and Resistance to Aminoglycoside Antibiotics through CrcZ in Pseudomonas aeruginosa","volume":"11","author":"Xia","year":"2020","journal-title":"mBio"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e00066-18","DOI":"10.1128\/mBio.00066-18","article-title":"Ethanolamine Utilization in Bacteria","volume":"9","author":"Kaval","year":"2018","journal-title":"mBio"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1128\/JB.00357-16","article-title":"Ethanolamine Catabolism in Pseudomonas aeruginosa PAO1 Is Regulated by the Enhancer-Binding Protein EatR (PA4021) and the Alternative Sigma Factor RpoN","volume":"198","author":"Lundgren","year":"2016","journal-title":"J. Bacteriol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/BF00223517","article-title":"Choline transport in Pseudomonas aeruginosa","volume":"85","author":"Salvano","year":"1989","journal-title":"Mol. Cell. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1128\/JB.00160-11","article-title":"Roles of three transporters, CbcXWV, BetT1, and BetT3, in Pseudomonas aeruginosa choline uptake for catabolism","volume":"193","author":"Malek","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1128\/AEM.03565-12","article-title":"Homeostasis and catabolism of choline and glycine betaine: Lessons from Pseudomonas aeruginosa","volume":"79","author":"Wargo","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1128\/JB.01055-13","article-title":"Characterization of the GbdR regulon in Pseudomonas aeruginosa","volume":"196","author":"Hampel","year":"2014","journal-title":"J. Bacteriol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zarzycki-Siek, J., Norris, M.H., Kang, Y., Sun, Z., Bluhm, A.P., McMillan, I.A., and Hoang, T.T. (2013). Elucidating the Pseudomonas aeruginosa fatty acid degradation pathway: Identification of additional fatty acyl-CoA synthetase homologues. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064554"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kang, Y., Zarzycki-Siek, J., Walton, C.B., Norris, M.H., and Hoang, T.T. (2010). Multiple FadD acyl-CoA synthetases contribute to differential fatty acid degradation and virulence in Pseudomonas aeruginosa. PLoS ONE, 5.","DOI":"10.1371\/annotation\/a55051c6-25dc-4548-912e-bf339830668e"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e3805","DOI":"10.21769\/BioProtoc.3805","article-title":"Murine Acute Pneumonia Model of Pseudomonas aeruginosa Lung Infection","volume":"10","author":"Pan","year":"2020","journal-title":"Bio-Protocol"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Weng, Y., Chen, F., Liu, Y., Zhao, Q., Chen, R., Pan, X., Liu, C., Cheng, Z., Jin, S., and Jin, Y. (2016). Pseudomonas aeruginosa Enolase Influences Bacterial Tolerance to Oxidative Stresses and Virulence. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.01999"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e0133925","DOI":"10.1128\/spectrum.01339-25","article-title":"The fatty acid synthesis gene fabY affects lipopolysaccharide synthesis and colistin susceptibility in Pseudomonas aeruginosa","volume":"13","author":"Zhou","year":"2025","journal-title":"Microbiol. Spectr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1093\/nar\/gkad059","article-title":"Regulatory and structural mechanisms of PvrA-mediated regulation of the PQS quorum-sensing system and PHA biosynthesis in Pseudomonas aeruginosa","volume":"51","author":"Pan","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wargo, M.J. (2013). Choline catabolism to glycine betaine contributes to Pseudomonas aeruginosa survival during murine lung infection. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056850"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3316","DOI":"10.1128\/jb.171.6.3316-3323.1989","article-title":"Functions required for vitamin B12-dependent ethanolamine utilization in Salmonella typhimurium","volume":"171","author":"Roof","year":"1989","journal-title":"J. Bacteriol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7157","DOI":"10.1128\/JB.00838-09","article-title":"Comparative genomics of ethanolamine utilization","volume":"191","author":"Tsoy","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/mmi.14962","article-title":"Localization and interaction studies of the Salmonella enterica ethanolamine ammonia-lyase (EutBC), its reactivase (EutA), and the EutT corrinoid adenosyltransferase","volume":"118","author":"Costa","year":"2022","journal-title":"Mol. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1128\/IAI.01008-08","article-title":"GbdR regulates Pseudomonas aeruginosa plcH and pchP transcription in response to choline catabolites","volume":"77","author":"Wargo","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1099\/mic.0.000502","article-title":"Pseudomonas aeruginosa gbdR gene is transcribed from a \u03c354-dependent promoter under the control of NtrC\/CbrB, IHF and BetI","volume":"163","author":"Primo","year":"2017","journal-title":"Microbiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e00790-18","DOI":"10.1128\/mBio.00790-18","article-title":"Loss of Ethanolamine Utilization in Enterococcus faecalis Increases Gastrointestinal Tract Colonization","volume":"9","author":"Kaval","year":"2018","journal-title":"mBio"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1462-2920.2010.02334.x","article-title":"Enterohaemorrhagic Escherichia coli gains a competitive advantage by using ethanolamine as a nitrogen source in the bovine intestinal content","volume":"13","author":"Bertin","year":"2011","journal-title":"Environ. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17480","DOI":"10.1073\/pnas.1107857108","article-title":"Intestinal inflammation allows Salmonella to use ethanolamine to compete with the microbiota","volume":"108","author":"Thiennimitr","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1073\/pnas.0511100103","article-title":"An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants","volume":"103","author":"Liberati","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nprot.2006.24","article-title":"mini-Tn7 insertion in bacteria with single attTn7 sites: Example Pseudomonas aeruginosa","volume":"1","author":"Choi","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7188","DOI":"10.1128\/jb.172.12.7188-7199.1990","article-title":"Characterization of the type a flagellin gene from Pseudomonas aeruginosa PAK","volume":"172","author":"Totten","year":"1990","journal-title":"J. Bacteriol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/7\/680\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T06:42:31Z","timestamp":1782801751000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/7\/680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,26]]},"references-count":43,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["pathogens15070680"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15070680","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,26]]}}}