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Here the effects of simulated microgravity (S\u00b5G) on gene expression and genome evolution of <jats:italic>E. coli<\/jats:italic> REL606, a strain evolved terrestrially for 35\u00a0years, is explored. The transcriptomic changes for glucose-limited and glucose-replete conditions over 24\u00a0h illustrate that S\u00b5G increased the expression of genes involved in stress response, biofilm, and metabolism. A greater number of differentially expressed genes related to the general stress response (GSR) and biofilm formation is observed in simulated microgravity cultures under glucose-limited conditions in comparison to glucose-replete conditions. Longer term S\u00b5G culture under glucose-limited conditions led to the accumulation of unique mutations when compared to control cultures, particularly in the <jats:italic>mraZ\/fruR<\/jats:italic> intergenic region and the <jats:italic>elyC gene<\/jats:italic>, suggesting changes in peptidoglycan and enterobacterial common antigen (ECA) production. These findings highlight the physiological and genomic adaptations of <jats:italic>E. coli<\/jats:italic> to microgravity, offering a foundation for future research into the long-term effects of space conditions on bacterial evolution.<\/jats:p>","DOI":"10.1186\/s12866-025-04064-7","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T03:01:00Z","timestamp":1749438060000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Simulated microgravity triggers a membrane adaptation to stress in E. coli REL606"],"prefix":"10.1186","volume":"25","author":[{"given":"Brittney","family":"Lozzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Adepoju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh L.","family":"Espinoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Padgen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena","family":"Parra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ricco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Castro-Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey E.","family":"Barrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubrie","family":"O\u2019Rourke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"4064_CR1","doi-asserted-by":"crossref","unstructured":"Arunasri K, Adil M, Charan KV, Suvro C, Reddy SH, Shivaji S. 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