{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:54:43Z","timestamp":1791327283346,"version":"4.3.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:00:00Z","timestamp":1495065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:00:00Z","timestamp":1495065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Exolysin (ExlA) is a recently-identified pore-forming toxin secreted by a subset of <jats:italic>Pseudomonas aeruginosa<\/jats:italic> strains identified worldwide and devoid of Type III secretion system (T3SS), a major virulence factor. Here, we characterized at the ultrastructural level the lesions caused by an ExlA-secreting strain, CLJ1, in mouse infected lungs. CLJ1 induced necrotic lesions in pneumocytes and endothelial cells, resulting in alveolo-vascular barrier breakdown. Ectopic expression of ExlA in an <jats:italic>exlA<\/jats:italic>-negative strain induced similar tissue injuries. In addition, ExlA conferred on bacteria the capacity to proliferate in lungs and to disseminate in secondary organs, similar to bacteria possessing a functional T3SS. CLJ1 did not promote a strong neutrophil infiltration in the alveoli, owing to the weak pro-inflammatory cytokine reaction engendered by the strain. However, CLJ1 was rapidly eliminated from the blood in a bacteremia model, suggesting that it can be promptly phagocytosed by immune cells. Together, our study ascribes to ExlA-secreting bacteria the capacity to proliferate in the lung and to damage pulmonary tissues, thereby promoting metastatic infections, in absence of substantial immune response exacerbation.<\/jats:p>","DOI":"10.1038\/s41598-017-02349-0","type":"journal-article","created":{"date-parts":[[2017,5,12]],"date-time":"2017-05-12T13:55:09Z","timestamp":1494597309000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Pseudomonas aeruginosa Exolysin promotes bacterial growth in lungs, alveolar damage and bacterial dissemination"],"prefix":"10.1038","volume":"7","author":[{"given":"St\u00e9phanie","family":"Bouillot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Munro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8758-7681","authenticated-orcid":false,"given":"Benoit","family":"Gallet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeline","family":"Reboud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Cretin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Golovkine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Schoehn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Attr\u00e9e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Lemichez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Huber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,18]]},"reference":[{"key":"2349_CR1","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1111\/2049-632X.12033","volume":"67","author":"SL Gellatly","year":"2013","unstructured":"Gellatly, S. L. & Hancock, R. E. Pseudomonas aeruginosa: new insights into pathogenesis and host defenses. Pathogens and disease \n                           67, 159\u2013173, doi:10.1111\/2049-632X.12033 (2013).","journal-title":"Pathogens and disease"},{"key":"2349_CR2","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1111\/j.1440-1843.2010.01819.x","volume":"15","author":"BJ Williams","year":"2010","unstructured":"Williams, B. J., Dehnbostel, J. & Blackwell, T. S. Pseudomonas aeruginosa: host defence in lung diseases. Respirology \n                           15, 1037\u20131056, doi:10.1111\/j.1440-1843.2010.01819.x (2010).","journal-title":"Respirology"},{"key":"2349_CR3","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1146\/annurev.micro.62.081307.162848","volume":"62","author":"Q Deng","year":"2008","unstructured":"Deng, Q. & Barbieri, J. T. Molecular mechanisms of the cytotoxicity of ADP-ribosylating toxins. Annual review of microbiology \n                           62, 271\u2013288, doi:10.1146\/annurev.micro.62.081307.162848 (2008).","journal-title":"Annual review of microbiology"},{"key":"2349_CR4","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/nrmicro2199","volume":"7","author":"AR Hauser","year":"2009","unstructured":"Hauser, A. R. The type III secretion system of Pseudomonas aeruginosa: infection by injection. Nature reviews \n                           7, 654\u2013665, doi:10.1038\/nrmicro2199 (2009).","journal-title":"Nature reviews"},{"key":"2349_CR5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/2052-0492-2-10","volume":"2","author":"T Sawa","year":"2014","unstructured":"Sawa, T. The molecular mechanism of acute lung injury caused by Pseudomonas aeruginosa: from bacterial pathogenesis to host response. J Intensive Care \n                           2, 10, doi:10.1186\/2052-0492-2-10 (2014).","journal-title":"J Intensive Care"},{"key":"2349_CR6","doi-asserted-by":"publisher","first-page":"3998","DOI":"10.1128\/IAI.68.7.3998-4004.2000","volume":"68","author":"M Allewelt","year":"2000","unstructured":"Allewelt, M., Coleman, F. T., Grout, M., Priebe, G. P. & Pier, G. B. Acquisition of expression of the Pseudomonas aeruginosa ExoU cytotoxin leads to increased bacterial virulence in a murine model of acute pneumonia and systemic spread. Infection and immunity \n                           68, 3998\u20134004, doi:10.1128\/IAI.68.7.3998-4004.2000 (2000).","journal-title":"Infection and immunity"},{"key":"2349_CR7","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1097\/00003246-200203000-00005","volume":"30","author":"AR Hauser","year":"2002","unstructured":"Hauser, A. R. et al. Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Critical care medicine \n                           30, 521\u2013528, doi:10.1097\/00003246-200203000-00005 (2002).","journal-title":"Critical care medicine"},{"key":"2349_CR8","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1097\/CCM.0b013e31821e899f","volume":"39","author":"R Le Berre","year":"2011","unstructured":"Le Berre, R. et al. Relative contribution of three main virulence factors in Pseudomonas aeruginosa pneumonia. Critical care medicine \n                           39, 2113\u20132120, doi:10.1097\/CCM.0b013e31821e899f (2011).","journal-title":"Critical care medicine"},{"key":"2349_CR9","doi-asserted-by":"publisher","first-page":"6969","DOI":"10.1128\/IAI.72.12.6969-6977.2004","volume":"72","author":"CM Shaver","year":"2004","unstructured":"Shaver, C. M. & Hauser, A. R. Relative contributions of Pseudomonas aeruginosa ExoU, ExoS, and ExoT to virulence in the lung. Infection and immunity \n                           72, 6969\u20136977, doi:10.1128\/IAI.72.12.6969-6977.2004 (2004).","journal-title":"Infection and immunity"},{"key":"2349_CR10","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1128\/IAI.73.3.1706-1713.2005","volume":"73","author":"RE Vance","year":"2005","unstructured":"Vance, R. E., Rietsch, A. & Mekalanos, J. J. Role of the type III secreted exoenzymes S, T, and Y in systemic spread of Pseudomonas aeruginosa PAO1 in vivo. Infection and immunity \n                           73, 1706\u20131713, doi:10.1128\/IAI.73.3.1706-1713.2005 (2005).","journal-title":"Infection and immunity"},{"key":"2349_CR11","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.chom.2014.01.003","volume":"15","author":"S Elsen","year":"2014","unstructured":"Elsen, S. et al. A type III secretion negative clinical strain of Pseudomonas aeruginosa employs a two-partner secreted exolysin to induce hemorrhagic pneumonia. Cell Host Microbe \n                           15, 164\u2013176, doi:10.1016\/j.chom.2014.01.003 (2014).","journal-title":"Cell Host Microbe"},{"key":"2349_CR12","doi-asserted-by":"publisher","DOI":"10.1111\/1758-2229.12443","author":"P Huber","year":"2016","unstructured":"Huber, P., Basso, P., Reboud, E. & Attree, I. Pseudomonas aeruginosa renews its virulence factors. Environ Microbiol Rep. doi:10.1111\/1758-2229.12443 (2016).","journal-title":"Environ Microbiol Rep"},{"key":"2349_CR13","doi-asserted-by":"publisher","first-page":"3425","DOI":"10.1111\/1462-2920.13262","volume":"18","author":"E Reboud","year":"2016","unstructured":"Reboud, E. et al. Phenotype and toxicity of the recently discovered exlA-positive Pseudomonas aeruginosa strains collected worldwide. Environ Microbiol \n                           18, 3425\u20133439, doi:10.1111\/1462-2920.13262 (2016).","journal-title":"Environ Microbiol"},{"key":"2349_CR14","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1007\/s00134-006-0497-7","volume":"33","author":"F Ader","year":"2007","unstructured":"Ader, F. et al. Inhaled nitric oxide increases endothelial permeability in Pseudomonas aeruginosa pneumonia. Intensive care medicine \n                           33, 503\u2013510, doi:10.1007\/s00134-006-0497-7 (2007).","journal-title":"Intensive care medicine"},{"key":"2349_CR15","doi-asserted-by":"publisher","first-page":"e106873","DOI":"10.1371\/journal.pone.0106873","volume":"9","author":"M De Simone","year":"2014","unstructured":"De Simone, M. et al. Host genetic background influences the response to the opportunistic Pseudomonas aeruginosa infection altering cell-mediated immunity and bacterial replication. PloS one \n                           9, e106873, doi:10.1371\/journal.pone.0106873 (2014).","journal-title":"PloS one"},{"key":"2349_CR16","first-page":"L551","volume":"267","author":"I Kudoh","year":"1994","unstructured":"Kudoh, I., Wiener-Kronish, J. P., Hashimoto, S., Pittet, J. F. & Frank, D. Exoproduct secretions of Pseudomonas aeruginosa strains influence severity of alveolar epithelial injury. The American journal of physiology \n                           267, L551\u2013556 (1994).","journal-title":"The American journal of physiology"},{"key":"2349_CR17","doi-asserted-by":"publisher","first-page":"e1004945","DOI":"10.1371\/journal.ppat.1004945","volume":"11","author":"SM Rangel","year":"2015","unstructured":"Rangel, S. M., Diaz, M. H., Knoten, C. A., Zhang, A. & Hauser, A. R. The Role of ExoS in Dissemination of Pseudomonas aeruginosa during Pneumonia. 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Infection and immunity \n                           73, 1695\u20131705, doi:10.1128\/IAI.73.3.1695-1705.2005 (2005).","journal-title":"Infection and immunity"},{"key":"2349_CR20","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1128\/iai.63.5.1718-1724.1995","volume":"63","author":"C Morissette","year":"1995","unstructured":"Morissette, C., Skamene, E. & Gervais, F. Endobronchial inflammation following Pseudomonas aeruginosa infection in resistant and susceptible strains of mice. Infection and immunity \n                           63, 1718\u20131724 (1995).","journal-title":"Infection and immunity"},{"key":"2349_CR21","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1165\/ajrcmb.20.4.3223","volume":"20","author":"M Tam","year":"1999","unstructured":"Tam, M., Snipes, G. J. & Stevenson, M. M. Characterization of chronic bronchopulmonary Pseudomonas aeruginosa infection in resistant and susceptible inbred mouse strains. 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Cell Host Microbe \n                           20, 36\u201348, doi:10.1016\/j.chom.2016.05.023 (2016).","journal-title":"Cell Host Microbe"},{"key":"2349_CR24","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1172\/JCI7124","volume":"104","author":"K Kurahashi","year":"1999","unstructured":"Kurahashi, K. et al. Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. The Journal of clinical investigation \n                           104, 743\u2013750, doi:10.1172\/JCI7124 (1999).","journal-title":"The Journal of clinical investigation"},{"key":"2349_CR25","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1128\/CMR.00118-13","volume":"27","author":"SJ Dando","year":"2014","unstructured":"Dando, S. J. et al. Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion. Clin Microbiol Rev \n                           27, 691\u2013726, doi:10.1128\/CMR.00118-13 (2014).","journal-title":"Clin Microbiol Rev"},{"key":"2349_CR26","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1128\/MMBR.00052-12","volume":"77","author":"FC Los","year":"2013","unstructured":"Los, F. C., Randis, T. M., Aroian, R. V. & Ratner, A. J. Role of pore-forming toxins in bacterial infectious diseases. Microbiol Mol Biol Rev \n                           77, 173\u2013207, doi:10.1128\/MMBR.00052-12 (2013).","journal-title":"Microbiol Mol Biol Rev"},{"key":"2349_CR27","doi-asserted-by":"publisher","first-page":"3898","DOI":"10.1128\/JB.187.11.3898-3902.2005","volume":"187","author":"S Bleves","year":"2005","unstructured":"Bleves, S., Soscia, C., Nogueira-Orlandi, P., Lazdunski, A. & Filloux, A. Quorum sensing negatively controls type III secretion regulon expression in Pseudomonas aeruginosa PAO1. Journal of bacteriology \n                           187, 3898\u20133902, doi:10.1128\/JB.187.11.3898-3902.2005 (2005).","journal-title":"Journal of bacteriology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-02349-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-02349-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-02349-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T04:27:11Z","timestamp":1671769631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-02349-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,18]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["2349"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-02349-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,18]]},"assertion":[{"value":"18 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"2120"}}