{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:56:25Z","timestamp":1790801785577,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011453","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000}}],"reference-count":94,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:00:00Z","timestamp":1717113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R33HL137077"],"award-info":[{"award-number":["R33HL137077"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL142587"],"award-info":[{"award-number":["R01HL142587"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["BOMBER18G0"],"award-info":[{"award-number":["BOMBER18G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pediatric Scientist Development Program - Association of Medical School Pediatric Department Chairs","award":["K12HD000850-34"],"award-info":[{"award-number":["K12HD000850-34"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32A1049820"],"award-info":[{"award-number":["T32A1049820"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["LIMOLI19R3"],"award-info":[{"award-number":["LIMOLI19R3"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Mucosa-associated biofilms are associated with many human disease states, but the host mechanisms promoting biofilm remain unclear. In chronic respiratory diseases like cystic fibrosis (CF),\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    establishes chronic infection through biofilm formation.\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    can be attracted to interspecies biofilms through potassium currents emanating from the biofilms. We hypothesized that\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    could, similarly, sense and respond to the potassium efflux from human airway epithelial cells (AECs) to promote biofilm. Using respiratory epithelial co-culture biofilm imaging assays of\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    grown in association with CF bronchial epithelial cells (CFBE41o\n                    <jats:sup>-<\/jats:sup>\n                    ), we found that\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    biofilm was increased by potassium efflux from AECs, as examined by potentiating large conductance potassium channel, BK\n                    <jats:sub>Ca<\/jats:sub>\n                    (NS19504) potassium efflux. This phenotype is driven by increased bacterial attachment and increased coalescence of bacteria into aggregates. Conversely, biofilm formation was reduced when AECs were treated with a BK\n                    <jats:sub>Ca<\/jats:sub>\n                    blocker (paxilline). Using an agar-based macroscopic chemotaxis assay, we determined that\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    chemotaxes toward potassium and screened transposon mutants to discover that disruption of the high-sensitivity potassium transporter, KdpFABC, and the two-component potassium sensing system, KdpDE, reduces\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    potassium chemotaxis. In respiratory epithelial co-culture biofilm imaging assays, a KdpFABCDE deficient\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    strain demonstrated reduced biofilm growth in association with AECs while maintaining biofilm formation on abiotic surfaces. Furthermore, we determined that the Kdp operon is expressed\n                    <jats:italic>in vivo<\/jats:italic>\n                    in people with CF and the genes are conserved in CF isolates. Collectively, these data suggest that\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    biofilm formation can be increased by attracting bacteria to the mucosal surface and enhancing coalescence into microcolonies through aberrant AEC potassium efflux sensed by the KdpFABCDE system. These findings suggest host electrochemical signaling can enhance biofilm, a novel host-pathogen interaction, and potassium flux could be a therapeutic target to prevent chronic infections in diseases with mucosa-associated biofilms, like CF.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011453","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T16:34:00Z","timestamp":1717173240000},"page":"e1011453","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Pseudomonas aeruginosa senses and responds to epithelial potassium flux via Kdp operon to promote biofilm"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4545-966X","authenticated-orcid":true,"given":"Glenn J.","family":"Rapsinski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia 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R.","family":"Armbruster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Zemke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Limoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4767-6238","authenticated-orcid":true,"given":"Jennifer M.","family":"Bomberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"issue":"9","key":"ppat.1011453.ref001","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nrmicro.2016.94","article-title":"Biofilms: an emergent form of bacterial life","volume":"14","author":"HC Flemming","year":"2016","journal-title":"Nat Rev 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