{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T20:54:42Z","timestamp":1760648082482,"version":"3.37.3"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10 OD021758-01A1"],"award-info":[{"award-number":["S10 OD021758-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10 OD030250-01A1"],"award-info":[{"award-number":["S10 OD030250-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Katie Rose Foundation"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>In cystic fibrosis (CF), there is abnormal translocation and function of the cystic fibrosis transmembrane conductance regulator (CFTR) and an upregulation of the epithelial sodium channel (ENaC). This leads to hyperabsorption of sodium and fluid from the airway, dehydrated mucus, and an increased risk of respiratory infections. In this study, we performed a proteomic assessment of differentially regulated proteins from CF and non-CF small airway epithelial cells (SAEC) that are sensitive to <jats:italic>Mycobacterium avium<\/jats:italic>. CF SAEC and normal non-CF SAEC were infected with <jats:italic>M<\/jats:italic>. <jats:italic>avium<\/jats:italic> before the cells were harvested for protein. Protein kinase C (PKC) activity was greater in the CF cells compared to the non-CF cells, but the activity was significantly attenuated in both cell types after infection with <jats:italic>M<\/jats:italic>. <jats:italic>avium<\/jats:italic> compared to vehicle. Western blot and densitometric analysis showed a significant increase in cathepsin B protein expression in <jats:italic>M<\/jats:italic>. <jats:italic>avium<\/jats:italic> infected CF cells. Myristoylated alanine rich C-kinase substrate (MARCKS) protein was one of several differentially expressed proteins between the groups that was identified by mass spectrometry-based proteomics. Total MARCKS protein expression was greater in CF cells compared to non-CF cells. Phosphorylation of MARCKS at serine 163 was also greater in CF cells compared to non-CF cells after treating both groups of cells with <jats:italic>M<\/jats:italic>. <jats:italic>avium<\/jats:italic>. Taken together, MARCKS protein is upregulated in CF cells and there is decreased phosphorylation of the protein due to a decrease in PKC activity and presumably increased cathepsin B mediated proteolysis of the protein after <jats:italic>M<\/jats:italic>. <jats:italic>avium<\/jats:italic> infection.<\/jats:p>","DOI":"10.1371\/journal.pone.0308299","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T17:23:17Z","timestamp":1729099397000},"page":"e0308299","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mycobacterium avium inhibits protein kinase C and MARCKS phosphorylation in human cystic fibrosis and non-cystic fibrosis cells"],"prefix":"10.1371","volume":"19","author":[{"given":"Kevin J.","family":"Kokesh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niharika","family":"Bala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunus E.","family":"Dogan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Van-Anh L.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4381-1172","authenticated-orcid":true,"given":"Abdel","family":"Alli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,10,16]]},"reference":[{"issue":"1","key":"pone.0308299.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ccm.2015.10.002","article-title":"Epidemiology of Cystic Fibrosis","volume":"37","author":"KA Spoonhower","year":"2016","journal-title":"Clin Chest Med"},{"issue":"11","key":"pone.0308299.ref002","doi-asserted-by":"crossref","DOI":"10.3390\/cells11111769","article-title":"CFTR Modulators in People with Cystic Fibrosis: Real-World Evidence in France","volume":"11","author":"L Regard","year":"2022","journal-title":"Cells"},{"issue":"4","key":"pone.0308299.ref003","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s40506-016-0092-6","article-title":"Nontuberculous Mycobacteria in Cystic Fibrosis","volume":"8","author":"K Skolnik","year":"2016","journal-title":"Curr Treat Options Infect Dis"},{"issue":"3","key":"pone.0308299.ref004","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0272-5231(02)00014-X","article-title":"Nontuberculous mycobacteria in the environment","volume":"23","author":"JO Falkinham","year":"2002","journal-title":"Clin Chest Med"},{"issue":"3","key":"pone.0308299.ref005","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3201\/eid1703.101510","article-title":"Nontuberculous mycobacteria from household plumbing of patients with nontuberculous mycobacteria disease","volume":"17","author":"JO Falkinham","year":"2011","journal-title":"Emerg Infect Dis"},{"issue":"3","key":"pone.0308299.ref006","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1055\/s-0038-1651495","article-title":"Nontuberculous Mycobacteria in Cystic Fibrosis","volume":"39","author":"BS Furukawa","year":"2018","journal-title":"Semin Respir Crit Care Med"},{"issue":"1","key":"pone.0308299.ref007","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1513\/AnnalsATS.201309-310OC","article-title":"Clinical significance of a first positive nontuberculous mycobacteria culture in cystic fibrosis","volume":"11","author":"SL Martiniano","year":"2014","journal-title":"Ann Am Thorac Soc"},{"issue":"5","key":"pone.0308299.ref008","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1164\/rccm.201405-0884OC","article-title":"Nontuberculous mycobacteria among patients with cystic fibrosis in the United States: screening practices and environmental risk","volume":"190","author":"J Adjemian","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0308299.ref009","doi-asserted-by":"crossref","first-page":"809014","DOI":"10.1155\/2015\/809014","article-title":"General Overview on Nontuberculous Mycobacteria, Biofilms, and Human Infection","volume":"2015","author":"S Faria","year":"2015","journal-title":"J Pathog"},{"issue":"6","key":"pone.0308299.ref010","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1164\/rccm.200207-678OC","article-title":"Nontuberculous mycobacteria. 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