{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T07:00:25Z","timestamp":1793430025368,"version":"4.5.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T00:00:00Z","timestamp":1572220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T00:00:00Z","timestamp":1572220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Microbiol"],"DOI":"10.1038\/s41564-019-0579-2","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T17:06:18Z","timestamp":1572282378000},"page":"2136-2145","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Breakdown of Vibrio cholerae biofilm architecture induced by antibiotics disrupts community barrier function"],"prefix":"10.1038","volume":"4","author":[{"given":"Francisco","family":"D\u00edaz-Pascual","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4924-6402","authenticated-orcid":false,"given":"Raimo","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lempp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Vidakovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boya","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Jeckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai M.","family":"Thormann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fitnat H.","family":"Yildiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rn","family":"Dunkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6677-555X","authenticated-orcid":false,"given":"Hannes","family":"Link","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1751-4895","authenticated-orcid":false,"given":"Carey D.","family":"Nadell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7340-2444","authenticated-orcid":false,"given":"Knut","family":"Drescher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,28]]},"reference":[{"key":"579_CR1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nature10388","volume":"477","author":"VM D\u2019Costa","year":"2011","unstructured":"D\u2019Costa, V. M. et al. Antibiotic resistance is ancient. Nature 477, 457\u2013461 (2011).","journal-title":"Nature"},{"key":"579_CR2","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1126\/science.aag0822","volume":"353","author":"M Baym","year":"2016","unstructured":"Baym, M. et al. Spatiotemporal microbial evolution on antibiotic landscapes. Science 353, 1147\u20131151 (2016).","journal-title":"Science"},{"key":"579_CR3","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/nature03912","volume":"436","author":"LR Hoffman","year":"2005","unstructured":"Hoffman, L. R. et al. Aminoglycoside antibiotics induce bacterial biofilm formation. Nature 436, 1171\u20131175 (2005).","journal-title":"Nature"},{"key":"579_CR4","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2014.06.046","volume":"158","author":"G Koch","year":"2014","unstructured":"Koch, G. et al. Evolution of resistance to a last-resort antibiotic in Staphylococcus aureus via bacterial competition. Cell 158, 1060\u20131071 (2014).","journal-title":"Cell"},{"key":"579_CR5","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1128\/CMR.00056-05","volume":"19","author":"H Jenssen","year":"2006","unstructured":"Jenssen, H., Hamill, P. & Hancock, R. E. W. Peptide antimicrobial agents. Clin. Microbiol. Rev. 19, 491\u2013511 (2006).","journal-title":"Clin. Microbiol. Rev."},{"key":"579_CR6","doi-asserted-by":"crossref","first-page":"13088","DOI":"10.1073\/pnas.1200791109","volume":"109","author":"A Houry","year":"2012","unstructured":"Houry, A. et al. Bacterial swimmers that infiltrate and take over the biofilm matrix. Proc. Natl Acad. Sci. USA 109, 13088\u201313093 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"579_CR7","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrmicro3270","volume":"12","author":"DI Andersson","year":"2014","unstructured":"Andersson, D. I. & Hughes, D. Microbiological effects of sublethal levels of antibiotics. Nat. Rev. Microbiol. 12, 465\u2013478 (2014).","journal-title":"Nat. Rev. Microbiol."},{"key":"579_CR8","unstructured":"O\u2019Neill, J. ed. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations (HM Government, 2014)."},{"key":"579_CR9","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.tim.2014.02.001","volume":"22","author":"H Van Acker","year":"2014","unstructured":"Van Acker, H., Van Dijck, P. & Coenye, T. Molecular mechanisms of antimicrobial tolerance and resistance in bacterial and fungal biofilms. Trends Microbiol. 22, 326\u2013333 (2014).","journal-title":"Trends Microbiol."},{"key":"579_CR10","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1128\/MMBR.00013-14","volume":"78","author":"D Lebeaux","year":"2014","unstructured":"Lebeaux, D., Ghigo, J.-M. & Beloin, C. Biofilm-related infections: bridging the gap between clinical management and fundamental aspects of recalcitrance toward antibiotics. Microbiol. Mol. Biol. Rev. 78, 510\u2013543 (2014).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"579_CR11","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/nrmicro.2017.99","volume":"15","author":"H Koo","year":"2017","unstructured":"Koo, H., Allan, R. N., Howlin, R. P., Stoodley, P. & Hall-Stoodley, L. Targeting microbial biofilms: current and prospective therapeutic strategies. Nat. Rev. Microbiol. 15, 740\u2013755 (2017).","journal-title":"Nat. Rev. Microbiol."},{"key":"579_CR12","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.cell.2018.01.037","volume":"172","author":"S Meylan","year":"2018","unstructured":"Meylan, S., Andrews, I. W. & Collins, J. J. Targeting antibiotic tolerance, pathogen by pathogen. Cell 172, 1228\u20131238 (2018).","journal-title":"Cell"},{"key":"579_CR13","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1093\/jac\/dkt072","volume":"68","author":"LG Garcia","year":"2013","unstructured":"Garcia, L. G. et al. Antibiotic activity against small-colony variants of Staphylococcus aureus: review of in vitro, animal and clinical data. J. Antimicrob. Chemother. 68, 1455\u20131464 (2013).","journal-title":"J. Antimicrob. Chemother."},{"key":"579_CR14","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1128\/AAC.02135-12","volume":"57","author":"BW Kwan","year":"2013","unstructured":"Kwan, B. W., Valenta, J. A., Benedik, M. J. & Wood, T. K. Arrested protein synthesis increases persister-like cell formation. Antimicrob. Agents Chemother. 57, 1468\u20131473 (2013).","journal-title":"Antimicrob. Agents Chemother."},{"key":"579_CR15","doi-asserted-by":"crossref","first-page":"273","DOI":"10.4161\/viru.23987","volume":"4","author":"SS Grant","year":"2013","unstructured":"Grant, S. S. & Hung, D. T. Persistent bacterial infections, antibiotic tolerance, and the oxidative stress response. Virulence 4, 273\u2013283 (2013).","journal-title":"Virulence"},{"key":"579_CR16","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1128\/AAC.44.3.640-646.2000","volume":"44","author":"A Brooun","year":"2000","unstructured":"Brooun, A., Liu, S. & Lewis, K. A Dose-response study of antibiotic resistance in Pseudomonas aeruginosa biofilms. Antimicrob. Agents Chemother. 44, 640\u2013646 (2000).","journal-title":"Antimicrob. Agents Chemother."},{"key":"579_CR17","volume":"7","author":"SL Chua","year":"2016","unstructured":"Chua, S. L. et al. Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms. Nat. Commun. 7, 10750 (2016).","journal-title":"Nat. Commun."},{"key":"579_CR18","doi-asserted-by":"crossref","first-page":"4975","DOI":"10.1128\/JB.00732-13","volume":"195","author":"K Gupta","year":"2013","unstructured":"Gupta, K., Marques, C. N. H., Petrova, O. E. & Sauer, K. Antimicrobial tolerance of Pseudomonas aeruginosa biofilms is activated during an early developmental stage and requires the two-component hybrid SagS. J. Bacteriol. 195, 4975\u20134987 (2013).","journal-title":"J. Bacteriol."},{"key":"579_CR19","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3109\/1040841X.2013.841639","volume":"41","author":"M Okshevsky","year":"2015","unstructured":"Okshevsky, M. & Meyer, R. L. The role of extracellular DNA in the establishment, maintenance and perpetuation of bacterial biofilms. Crit. Rev. Microbiol. 41, 341\u2013352 (2015).","journal-title":"Crit. Rev. Microbiol."},{"key":"579_CR20","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nature02122","volume":"426","author":"T-F Mah","year":"2003","unstructured":"Mah, T.-F. et al. A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature 426, 306\u2013310 (2003).","journal-title":"Nature"},{"key":"579_CR21","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1126\/science.1211037","volume":"334","author":"D Nguyen","year":"2011","unstructured":"Nguyen, D. et al. Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Science 334, 982\u2013986 (2011).","journal-title":"Science"},{"key":"579_CR22","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.ijantimicag.2009.12.011","volume":"35","author":"N H\u00f8iby","year":"2010","unstructured":"H\u00f8iby, N., Bjarnsholt, T., Givskov, M., Molin, S. & Ciofu, O. Antibiotic resistance of bacterial biofilms. Int. J. Antimicrob. Agents 35, 322\u2013332 (2010).","journal-title":"Int. J. Antimicrob. Agents"},{"key":"579_CR23","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1111\/1462-2920.12155","volume":"15","author":"BS Tseng","year":"2013","unstructured":"Tseng, B. S. et al. The extracellular matrix protects Pseudomonas aeruginosa biofilms by limiting the penetration of tobramycin. Environ. Microbiol. 15, 2865\u20132878 (2013).","journal-title":"Environ. Microbiol."},{"key":"579_CR24","volume":"3","author":"JL Dale","year":"2017","unstructured":"Dale, J. L., Nilson, J. L., Barnes, A. M. T. & Dunny, G. M. Restructuring of Enterococcus faecalis biofilm architecture in response to antibiotic-induced stress. NPJ Biofilms Microbiomes 3, 15 (2017).","journal-title":"Biofilms Microbiomes"},{"key":"579_CR25","volume":"15","author":"KC Wong","year":"2015","unstructured":"Wong, K. C., Brown, A. M., Luscombe, G. M., Wong, S. J. & Mendis, K. Antibiotic use for Vibrio infections: important insights from surveillance data. BMC Infect. Dis. 15, 226 (2015).","journal-title":"BMC Infect. Dis."},{"key":"579_CR26","doi-asserted-by":"crossref","first-page":"E2066","DOI":"10.1073\/pnas.1601702113","volume":"113","author":"K Drescher","year":"2016","unstructured":"Drescher, K. et al. Architectural transitions in Vibrio cholerae biofilms at single-cell resolution. Proc. Natl Acad. Sci. USA 113, E2066\u2013E2072 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"579_CR27","doi-asserted-by":"crossref","first-page":"3359","DOI":"10.1016\/j.cub.2017.09.041","volume":"27","author":"PK Singh","year":"2017","unstructured":"Singh, P. K. et al. Vibrio cholerae combines individual and collective sensing to trigger biofilm dispersal. Curr. Biol. 27, 3359\u20133366 (2017).","journal-title":"Curr. Biol."},{"key":"579_CR28","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/s41567-018-0356-9","volume":"15","author":"R Hartmann","year":"2019","unstructured":"Hartmann, R. et al. Emergence of three-dimensional order and structure in growing biofilms. Nat. Phys. 15, 251\u2013256 (2019).","journal-title":"Nat. Phys."},{"key":"579_CR29","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/nrmicro2198","volume":"7","author":"DW Adams","year":"2009","unstructured":"Adams, D. W. & Errington, J. Bacterial cell division: assembly, maintenance and disassembly of the Z ring. Nat. Rev. Microbiol. 7, 642\u2013653 (2009).","journal-title":"Nat. Rev. Microbiol."},{"key":"579_CR30","doi-asserted-by":"crossref","first-page":"7017","DOI":"10.1021\/la401322k","volume":"29","author":"EJ Stewart","year":"2013","unstructured":"Stewart, E. J., Satorius, A. E., Younger, J. G. & Solomon, M. J. Role of environmental and antibiotic stress on Staphylococcus epidermidis biofilm microstructure. Langmuir 29, 7017\u20137024 (2013).","journal-title":"Langmuir"},{"key":"579_CR31","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1126\/science.1222981","volume":"337","author":"V Berk","year":"2012","unstructured":"Berk, V. et al. Molecular architecture and assembly principles of Vibrio cholerae biofilms. Science 337, 236\u2013239 (2012).","journal-title":"Science"},{"key":"579_CR32","first-page":"1","volume":"6","author":"JC Fong","year":"2017","unstructured":"Fong, J. C. et al. Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms. eLife 6, 1\u201322 (2017).","journal-title":"eLife"},{"key":"579_CR33","doi-asserted-by":"crossref","first-page":"10491","DOI":"10.1073\/pnas.1512424112","volume":"112","author":"DR Smith","year":"2015","unstructured":"Smith, D. R. et al. In situ proteolysis of the Vibrio cholerae matrix protein rbma promotes biofilm recruitment. Proc. Natl Acad. Sci. USA 112, 10491\u201310496 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"579_CR34","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1128\/JB.01569-06","volume":"189","author":"JCN Fong","year":"2007","unstructured":"Fong, J. C. N. & Yildiz, F. H. The rbmBCDEF gene cluster modulates development of rugose colony morphology and biofilm formation in Vibrio cholerae. J. Bacteriol. 189, 2319\u20132330 (2007).","journal-title":"J. Bacteriol."},{"key":"579_CR35","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/j.bpj.2015.10.004","volume":"109","author":"C Douarche","year":"2015","unstructured":"Douarche, C., Allain, J.-M. & Raspaud, E. Bacillus subtilis bacteria generate an internal mechanical force within a biofilm. Biophys. J. 109, 2195\u20132202 (2015).","journal-title":"Biophys. J."},{"key":"579_CR36","volume":"8","author":"J Yan","year":"2017","unstructured":"Yan, J., Nadell, C. D., Stone, H. A., Wingreen, N. S. & Bassler, B. L. Extracellular-matrix-mediated osmotic pressure drives Vibrio cholerae biofilm expansion and cheater exclusion. Nat. Commun. 8, 327 (2017).","journal-title":"Nat. Commun."},{"key":"579_CR37","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41564-017-0050-1","volume":"3","author":"L Vidakovic","year":"2018","unstructured":"Vidakovic, L., Singh, P. K., Hartmann, R., Nadell, C. D. & Drescher, K. Dynamic biofilm architecture confers individual and collective mechanisms of viral protection. Nat. Microbiol. 3, 26\u201331 (2018).","journal-title":"Nat. Microbiol"},{"key":"579_CR38","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1038\/ismej.2014.246","volume":"9","author":"CD Nadell","year":"2015","unstructured":"Nadell, C. D., Drescher, K., Wingreen, N. S. & Bassler, B. L. Extracellular matrix structure governs invasion resistance in bacterial biofilms. ISME J. 9, 1700\u20131709 (2015).","journal-title":"ISME J."},{"key":"579_CR39","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0168-1605(89)90037-8","volume":"9","author":"BR J\u00f8rgensen","year":"1989","unstructured":"J\u00f8rgensen, B. R. & Huss, H. H. Growth and activity of Shewanella putrefaciens isolated from spoiling fish. Int. J. Food Microbiol. 9, 51\u201362 (1989).","journal-title":"Int. J. Food Microbiol."},{"key":"579_CR40","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00248-003-1032-9","volume":"47","author":"N Kimata","year":"2004","unstructured":"Kimata, N., Nishino, T., Suzuki, S. & Kogure, K. Pseudomonas aeruginosa isolated from marine environments in Tokyo bay. Microb. Ecol. 47, 41\u201347 (2004).","journal-title":"Microb. Ecol."},{"key":"579_CR41","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1038\/s41396-019-0396-x","volume":"13","author":"CJ Brislawn","year":"2019","unstructured":"Brislawn, C. J. et al. Forfeiting the priority effect: turnover defines biofilm community succession. ISME J. 13, 1865\u20131877 (2019).","journal-title":"ISME J."},{"key":"579_CR42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0378-1119(95)00793-8","volume":"169","author":"K Skorupski","year":"1996","unstructured":"Skorupski, K. & Taylor, R. K. Positive selection vectors for allelic exchange. Gene 169, 47\u201352 (1996).","journal-title":"Gene"},{"key":"579_CR43","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1021\/acs.analchem.6b03731","volume":"89","author":"JC Guder","year":"2017","unstructured":"Guder, J. C., Schramm, T., Sander, T. & Link, H. Time-optimized isotope ratio LC\u2013MS\/MS for high-throughput quantification of primary metabolites. Anal. Chem. 89, 1624\u20131631 (2017).","journal-title":"Anal. Chem."},{"key":"579_CR44","doi-asserted-by":"crossref","first-page":"16077","DOI":"10.1038\/nmicrobiol.2016.77","volume":"1","author":"A Ducret","year":"2016","unstructured":"Ducret, A., Quardokus, E. M. & Brun, Y. V. MicrobeJ, a tool for high throughput bacterial cell detection and quantitative analysis. Nat. Microbiol. 1, 16077 (2016).","journal-title":"Nat. Microbiol."},{"key":"579_CR45","first-page":"e2437","volume":"47","author":"GA O\u2019Toole","year":"2011","unstructured":"O\u2019Toole, G. A. Microtiter dish biofilm formation assay. J. Vis. Exp. 47, e2437 (2011).","journal-title":"J. Vis. Exp."},{"key":"579_CR46","doi-asserted-by":"publisher","unstructured":"Hartmann, R. et al. BiofilmQ, a software tool for quantitative image analysis of microbial biofilm communities. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/735423 (2019).","DOI":"10.1101\/735423"},{"key":"579_CR47","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1111\/j.1365-2958.2006.05568.x","volume":"63","author":"S Beyhan","year":"2007","unstructured":"Beyhan, S. & Yildiz, F. H. Smooth to rugose phase variation in Vibrio cholerae can be mediated by a single nucleotide change that targets c-di-GMP signalling pathway. Mol. Microbiol 63, 995\u20131007 (2007).","journal-title":"Mol. Microbiol"}],"container-title":["Nature Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41564-019-0579-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41564-019-0579-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41564-019-0579-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T21:40:36Z","timestamp":1721943636000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41564-019-0579-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,28]]},"references-count":47,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["579"],"URL":"https:\/\/doi.org\/10.1038\/s41564-019-0579-2","relation":{},"ISSN":["2058-5276"],"issn-type":[{"value":"2058-5276","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,28]]},"assertion":[{"value":"5 December 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 September 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}