{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:17:51Z","timestamp":1791404271479,"version":"4.3.3"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013568","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000}}],"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic><jats:italic>Pseudomonas aeruginosa<\/jats:italic><\/jats:italic> is a hallmark pathogen of cystic fibrosis (CF) airway infections, capable of reaching high cell densities despite its limited ability to directly utilize mucin glycoproteins as a nutrient source. In the CF lung, however, <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic> may access preferred carbon sources (e.g., amino acids and short-chain fatty acids) through metabolic cross-feeding with co-colonizing mucin-degrading microbes. Although host-derived enzymes such as neutrophil elastase can also degrade mucins, the extent to which host-mediated mucin breakdown supports <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic> growth remains unclear. Thus, here we compared the nutritional impact of microbial versus host mucolytic activity on <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic> physiology. Analyses of CF sputum revealed patient-specific variability in mucin integrity that is shaped by both host and microbial factors. We demonstrate that mucin degradation by anaerobic bacteria through proteolysis, glycolysis, and fermentation, promotes robust <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic> growth, unlike mucin processed by neutrophil elastase alone. Targeted metabolomics identified acetate and propionate as key metabolites driving this cross-feeding, while transcriptomic and phenotypic analyses revealed that <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic> engages in diauxic growth on a broader set of mucin-derived substrates. Unexpectedly, cross-feeding with anaerobes triggered the induction of <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic> denitrification and fermentation pathways, suggesting redox remodeling despite being cultured under oxygen-replete conditions. Finally, the transcriptional profile of <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic> grown on anaerobe-conditioned mucins more closely resembled its <jats:italic>in vivo<\/jats:italic> gene expression, more so than when grown on intact or neutrophil-degraded mucins. Together, these findings provide new insight into the potential role of interspecies metabolic interactions in shaping pathogen physiology in the inflammatory, polymicrobial, and mucus-rich environment of the CF airways.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013568","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T17:37:07Z","timestamp":1759513027000},"page":"e1013568","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Host- and microbial-mediated mucin degradation differentially shape Pseudomonas aeruginosa physiology and gene expression"],"prefix":"10.1371","volume":"21","author":[{"given":"Sabrina J.","family":"Arif","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla M.","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey 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Carmody","year":"2018","journal-title":"PLoS One"},{"issue":"1","key":"ppat.1013568.ref031","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1006798","article-title":"Initial acquisition and succession of the cystic fibrosis lung microbiome is associated with disease progression in infants and preschool children","volume":"14","author":"MS Muhlebach","year":"2018","journal-title":"PLoS Pathog"},{"issue":"9","key":"ppat.1013568.ref032","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00153-21","article-title":"Anaerobic Microbiota Derived from the Upper Airways Impact Staphylococcus aureus Physiology","volume":"89","author":"SK Lucas","year":"2021","journal-title":"Infect Immun"},{"issue":"19","key":"ppat.1013568.ref033","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2221542120","article-title":"Application of a quantitative framework to improve the accuracy of a bacterial infection model","volume":"120","author":"GR Lewin","year":"2023","journal-title":"Proc Natl Acad Sci U 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Anaerobic Bacteria, in the Cystic Fibrosis Airway","volume":"192","author":"B Mirkovi\u0107","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"ppat.1013568.ref038","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1183\/09031936.00143614","article-title":"Short-chain fatty acids affect cystic fibrosis airway inflammation and bacterial growth","volume":"46","author":"P Ghorbani","year":"2015","journal-title":"Eur Respir J"},{"issue":"1","key":"ppat.1013568.ref039","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/1751-7915.13423","article-title":"Transcriptional regulation of central carbon metabolism in Pseudomonas aeruginosa","volume":"13","author":"SK Dolan","year":"2020","journal-title":"Microb Biotechnol"},{"issue":"1","key":"ppat.1013568.ref040","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0190599","article-title":"Mucin acts as a nutrient source and a signal for the differential expression of genes coding for cellular processes and virulence factors in Acinetobacter baumannii","volume":"13","author":"EJ Ohneck","year":"2018","journal-title":"PLoS One"},{"issue":"4","key":"ppat.1013568.ref041","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00767-15","article-title":"Pediatric cystic fibrosis sputum can be chemically dynamic, anoxic, and extremely reduced due to hydrogen sulfide formation","volume":"6","author":"ES Cowley","year":"2015","journal-title":"MBio"},{"issue":"2","key":"ppat.1013568.ref042","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cels.2017.06.005","article-title":"Why Do Fast-Growing Bacteria Enter Overflow Metabolism? Testing the Membrane Real Estate Hypothesis","volume":"5","author":"M Szenk","year":"2017","journal-title":"Cell Syst"},{"issue":"7","key":"ppat.1013568.ref043","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0023126","article-title":"Condition-dependent cell volume and concentration of Escherichia coli to facilitate data conversion for systems biology modeling","volume":"6","author":"B Volkmer","year":"2011","journal-title":"PLoS One"},{"issue":"2","key":"ppat.1013568.ref044","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.02684-19","article-title":"Contextual Flexibility in Pseudomonas aeruginosa Central Carbon Metabolism during Growth in Single Carbon Sources","volume":"11","author":"SK Dolan","year":"2020","journal-title":"mBio"},{"key":"ppat.1013568.ref045","doi-asserted-by":"crossref","first-page":"554","DOI":"10.3389\/fmicb.2014.00554","article-title":"Physiological levels of nitrate support anoxic growth by denitrification of Pseudomonas aeruginosa at growth rates reported in cystic fibrosis lungs and sputum","volume":"5","author":"L Line","year":"2014","journal-title":"Front Microbiol"},{"issue":"3","key":"ppat.1013568.ref046","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1172\/JCI0213870","article-title":"Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients","volume":"109","author":"D Worlitzsch","year":"2002","journal-title":"J Clin Invest"},{"issue":"33","key":"ppat.1013568.ref047","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2406234121","article-title":"Improvement of a mouse infection model to capture","volume":"121","author":"RP Duncan","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"ppat.1013568.ref048","doi-asserted-by":"crossref","DOI":"10.1099\/jmm.0.001708","article-title":"High-throughput quantification of microbial-derived organic acids in mucin-rich samples via reverse phase high performance liquid chromatography","volume":"72","author":"AR Villarreal","year":"2023","journal-title":"J Med Microbiol"},{"issue":"8","key":"ppat.1013568.ref049","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkz114","article-title":"The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads","volume":"47","author":"Y Liao","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"550","key":"ppat.1013568.ref050","first-page":"10","article-title":"Differential analysis of count data \u2013 the DESeq2 package","volume":"15","author":"M Love","year":"2014","journal-title":"Genome Biology"},{"key":"ppat.1013568.ref051","volume-title":"ggsunburst: Adjacency diagrams with ggplot2","author":"D Santesmasses","year":"2020"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1013568","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013568","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T18:02:26Z","timestamp":1759860146000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013568"}},"subtitle":[],"editor":[{"given":"Rohit","family":"Ruhal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,3]]},"references-count":51,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1013568","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,3]]}}}