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Extracellular DNA (eDNA) has a structural role in the formation of biofilms, can bind and shield biofilms from aminoglycosides, and induces antimicrobial peptide resistance mechanisms. Here, we provide evidence that eDNA is responsible for the acidification of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>planktonic cultures and biofilms. Further, we show that acidic pH and acidification via eDNA constitute a signal that is perceived by<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>to induce the expression of genes regulated by the PhoPQ and PmrAB two-component regulatory systems. Planktonic<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>cultured in exogenous 0.2% DNA or under acidic conditions demonstrates a 2- to 8-fold increase in aminoglycoside resistance. This resistance phenotype requires the aminoarabinose modification of lipid A and the production of spermidine on the bacterial outer membrane, which likely reduce the entry of aminoglycosides. Interestingly, the additions of the basic amino acid<jats:sc>l<\/jats:sc>-arginine and sodium bicarbonate neutralize the pH and restore<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>susceptibility to aminoglycosides, even in the presence of eDNA. These data illustrate that the accumulation of eDNA in biofilms and infection sites can acidify the local environment and that acidic pH promotes the<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>antibiotic resistance phenotype.<\/jats:p>","DOI":"10.1128\/aac.01650-15","type":"journal-article","created":{"date-parts":[[2015,11,10]],"date-time":"2015-11-10T04:09:28Z","timestamp":1447128568000},"page":"544-553","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":238,"title":["Extracellular DNA Acidifies Biofilms and Induces Aminoglycoside Resistance in Pseudomonas aeruginosa"],"prefix":"10.1128","volume":"60","author":[{"given":"Mike","family":"Wilton","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute of Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Charron-Mazenod","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute of Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute of Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Lewenza","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute of Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"},{"name":"Faculty of Science and Technology, Athabasca University, Athabasca, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2007.12.001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.295.5559.1487"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.05008.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2007.09.010"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/006031-0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2010.10.016"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.54.1.49"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.14.4449-4456.2004"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3109\/1040841X.2013.841639"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02839-07"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.03119-09"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2006\/004911-0"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2008.01658.x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06934.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218898110"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00001-13"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1479050503001066"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.15.4585-4592.2003"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.23.8066-8073.2004"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/009092-0"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00257-06"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1183\/09031936.93.03010019","article-title":"The origin of DNA associated with mucus glycoproteins in cystic fibrosis sputum","volume":"3","author":"Lethem MI","year":"1990","unstructured":"Lethem MI, James SL, Marriott C, Burke JF. 1990. 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