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Using a multi-omics approach on resected aspergillomas, we defined the genomic, transcriptional, and metabolic adaptations of P. aeruginosa within this polymicrobial niche. We reconstructed high-quality P. aeruginosa genomes and identified a conserved core genome, along with accessory genes for secondary metabolism, virulence, and antimicrobial resistance. Phylogenomics revealed heterogeneous evolutionary paths among co-colonizing strains. Metatranscriptomics showed stark physiological heterogeneity, from metabolically aggressive to stress-adapted states. High expression of phenazine, quorum-sensing (PQS), siderophore, and secretion-system operons was corroborated by metabolomic detection of phenazine-1-carboxylic acid and 2-heptylquinolin-4(1H)-one, confirming active bacterial antagonism in vivo. Concurrent Aspergillus fumigatus transcriptomics revealed the activation of oxidative stress responses, secondary metabolism (eg fumagillin), and iron scavenging, demonstrating reciprocal competition. Host transcriptomics revealed patient-specific immune signatures that correlated with the metabolic activity of the co-colonizers. This work provides an integrated systems-level analysis of the tri-kingdom aspergilloma ecosystem. P. aeruginosa persistence is driven by genomic plasticity and context-dependent expression of competitive pathways, shaped within a chronic inflammatory environment. These findings redefine aspergillomas as active polymicrobial consortia, establishing a framework for targeting resilient microbial communities in chronic lung disease.<\/jats:p>","DOI":"10.1093\/g3journal\/jkag063","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T18:35:51Z","timestamp":1773772551000},"source":"Crossref","is-referenced-by-count":3,"title":["<i>Pseudomonas aeruginosa<\/i>\n                    adaptation and persistence in the aspergilloma microbiome revealed by integrated multi-omics"],"prefix":"10.1093","volume":"16","author":[{"given":"Matheus Mertz","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo , Ribeir\u00e3o Preto, S\u00e3o Paulo CEP 14040-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University , Shanghai 200092 ,","place":["China"]},{"name":"Institute of Respiratory Medicine, School of Medicine, Tongji University , Shanghai 200092 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Fu","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Respiratory Medicine, School of Medicine, Tongji University , Shanghai 200092 ,","place":["China"]},{"name":"Department of Respiratory and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University , Shanghai 200092 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University , Shanghai 200092 ,","place":["China"]},{"name":"Institute of Respiratory Medicine, School of Medicine, Tongji University , Shanghai 200092 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2986-350X","authenticated-orcid":false,"given":"Gustavo H","family":"Goldman","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo , Ribeir\u00e3o Preto, S\u00e3o Paulo CEP 14040-903 ,","place":["Brazil"]},{"name":"National Institute of Science and Technology in Human Pathogenic Fungi , Ribeir\u00e3o Preto, S\u00e3o Paulo CEP 14040-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"2026090412113650600_jkag063-B1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-031-08491-1_1","volume-title":"Pseudomonas aeruginosa: biology, pathogenesis and control 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